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Currently viewing: S-01 | Summary001 Key | Read-across (Category)002 Weight of evidence | Read-across (Category)003 Weight of evidence | Read-across (Category)004 Weight of evidence | Read-across (Category)005 Weight of evidence | Read-across (Category)
No immunotoxicity data of sufficient quality are available for tungsten carbide (target substance). However, immunotoxicity data are available for sodium tungstate (source substance), which will be used for read across. Due to lower water solubility and lower toxicity for the target substance compared to the source substance, the resulting read across from the source substance to the target substance is appropriate as a conservative estimate of potential toxicity for this endpoint. In addition, read across is appropriate because the classification and labelling is more protective for the source substance than the target substance, the PBT/vPvB profile is the same, and the dose descriptors are, or are expected to be, lower for the source substance. For more details, refer to the attached description of the read-across approach.
To determine if sodium tungstate can cause an unnatural immune response, mice were exposed in utero by parental inhalation or ingestion of an estimated dose of 1 and 4 mg/kg/d, respectively; and inoculated with respiratory syncytial virus (within 2 weeks of weaning). Compared with controls, sodium tungstate treated animals presented significant spleen enlargement (splenomegaly); however, the nature of the hematological/immunological disease was inconclusive (Fastje et al., 2012).
Osterburg et al. (2014) tested if exposure to sodium tungstate can result in immune suppression. For this, parental male and female mice were orally exposed to 2, 62.5, 125, and 200 mg/kg/d for 28 d in a one-generation model and intraperitoneally injected with Staphylococcal enterotoxin. Exposure to sodium tungstate at the highest dose resulted in a decrease of activated cytotoxic T-cells and helper T-cells. In delayed-type hypersensitivity Type IV experiments, exposure to 200 mg/kg/d of sodium tungstate prior to primary and secondary antigen challenge significantly reduced footpad swelling. According to the authors, these results suggest that sodium tungstate could cause an immune suppression that may reduce host defense against pathogens.
Kelly et al. (2013) exposed mice for 16 weeks to sodium tungstate via the drinking water. Mice receiving 15, 200, or 1000 mg/L (oral doses estimated to be in the order of 50 and 250 mg/kg-day) had a significantly greater percentage of cells in the late pro-/large pre-B developmental stages. Tungstate did not alter erythrocyte and platelet counts, or hemoglobin and hematocrit levels, and neither caused liver toxicity as assessed by peripheral blood alanine aminotransferase (AST) and aspartate aminotransferase (ALT) enzyme levels. An increase in DNA damage in both whole marrow and isolated B cells at the lower tungsten concentration (15 mg/L), but not at the highest concentration (1000 mg/L), was also noted.
A US National Toxicology Program dose range finding report (US NTP, 2012) summarizes a mice immunotoxicity 28-day study to establish the potential effects on the immune system of female mice receiving sodium tungstate via drinking water at 125, 250, 500, 1000, and 2000 mg/L (estimated doses ranged from 30 to 500 mg/kg-day). Over the 28-day exposure period, sodium tungstate did not alter body weight, body weight gain, or the weights of the major organs of the immune system, the thymus and spleen. Total splenocyte number and both absolute values and percent values of spleen cell phenotypes were unaffected by sodium tungstate exposure (NTP, 2012). No effects were observed on T-dependent antibody responses, as evaluated using the antibody-forming cell response, the sheep red blood cell enzyme-linked immunosorbent assay (ELISA), and the keyhole limpet hemocyanin ELISA, suggesting that humoral (antibody) immunity is not adversely affected by sodium tungstate exposure (US NTP, 2012). The mixed leukocyte response and the cytotoxic T-lymphocyte responses presented some significant differences, but they were not dose responsive. Furthermore, no effects were observed on thein vivodelayed-type hypersensitivity response toCandida albicansor in the anti-CD3-mediated proliferation assay, suggesting that sodium tungstate does not affect cell-mediated immunity (US NTP, 2012).
Frawley et al. (2016) published a reinterpretation of the NTP study results on female B6C3F1/N mice study. The publication indicated that three different parameters of cell-mediated immunity were similarly affected at 1000 mg/L. T-cell proliferative responses against allogeneic leukocytes and anti-CD3 were decreased. Cytotoxic T-lymphocyte activity was decreased at all effector:target cell ratios examined. At 2000 mg/L, the absolute numbers of CD3+T-cell progenitor cells in bone marrow were increased but the alterations in B-lymphocyte and other progenitor cells were not significant. There were no effects on bone marrow DNA synthesis or colony forming capabilities. Tungstate-induced effects on humoral-mediated immunity, innate immunity, and splenocyte sub-populations were limited. Enhanced histopathology did not detect treatment-related lesions in any of the immune tissues.
The following information is considered for any hazard / risk assessment:
Overall, there are drinking water immunotoxicity 28 -day studies (Osterburg et al., 2014) conducted at doses (200 -250 mg/kg/d) that reported potential effects of sodium tungstate on innate, humoral or cell mediated immunities. US NTP sponsored standard testing studies at similar exposure doses (1000 mg/L≈245 mg/kg-day) found that the tungstate induced humoral-mediated immunity, innate immunity, and splenocyte sub-populations effects were limited.
In addition, female B6C3F1/N mice exposed to sodium tungstate in the drinking water demonstrated no effects on body weight, body weight gain or the weights of major organs of the immune system, the thymus and the spleen, over the 28-day exposure period.
No effects were observed on cell viabilities [total spleen cell numbers or on the absolute or percent values of splenic B-cells, T-cells, T-cell subsets, natural killer (NK) cells, or macrophages], humoral immunity examinations [e.g. antibody forming cell assay (AFC) response to sheep blood red blood cells [SRBC] in the plaque assays or on serum IgM antibody levels to SRBC or Keyhole limpet hemocyanin(KLH)], and cell-mediated immunity (no effects on NK cell activity). Exposure to sodium tungstate did not affect DNA synthesis of bone marrow cells, or colony-forming units following in vitro stimulation of isolated bone marrow cells with macrophage colony-M-CSF), granulocyte-macrophage colony-stimulating factor (GM-CSF), or erythroid colony-stimulating factor (E-CSF). Furthermore, no effects were observed on the in vivo delayed-type hypersensitivity (DTH) response toC. albicans.
The US NTP study suggests that exposure to sodium tungstate in drinking water may adversely affect cell-mediated immunity only following sensitization with an immune stimulating agent such as P815 mastocytoma cells), and as well as splenocyte proliferation against allogeneic leukocytes or the anti-CD3 antibody at 1000 mg/L only, as surprisingly, no effects were observed on cell-mediated immunity responses at 2000 mg/L (Frawley et al., 2016). Similarly, other studies have shown that tungstate-treated C57BL/6 mice exposed pup sin utero via water (15 ppm,ad libetum) and inhalation (3.33 mg/m3),and after weaning (15 ppm,ad libetum) developed significant splenomegaly when inoculated with the T-cell activating respiratory syncytial virus (RSV) (Fastje et al., 2012); and demonstrated suppression of activated TH and TCTL cells, when exposed parental (28-days) and pups (12-19 weeks after weaning) to 200 mg/kg-day and challenged with bacterial antigen staphylococcal enterotoxin (SEB) (Osterburg et al., 2014). However, in the absence of RSV or SEB challenge, tungstate had no effect on spleen size or T-cell populations.
In summary, sodium tungstate did not affect innate immunity, humoral immunity, or on developing hematopoietic cells in the bone marrow, and on unstimulated splenocyte phenotypes in female B6C3F1/N mice exposed via the drinking water. In addition, sodium tungstate did not adversely affect immune-organs of mice (thymus, spleen, mesenteric lymph node, popliteal lymph node, mucosa-associated lymphoid tissues, or bone marrow) and rats (McInturf et al, 2011). As potential cell-mediated immune effects at 1000 mg/L (≈dose level 247 mg/kg/d) are only observed under conditions of co-exposure to an immune-stimulating agent (such as tumor cells or genetically dissimilar leukocytes) rather than direct action. Based on this, sodium tungstate is not considered a direct immunotoxicant.
Effect on immunotoxicity: via oral route
Dose descriptor:
132.11 mg/kg bw/day
Quality of whole database:
Scientfically sound study similar to OECD guidelines. However as this study is used in the context of a read across, Klimisch 2 is assigned.
Effect on immunotoxicity: via inhalation route
Effect on immunotoxicity: via dermal route
No (developmental) immunotoxicity data of sufficient quality are available for tungsten carbide (target substance). Bioaccessibility studies (IITRI 2010), indicate that the bioavailability of tungsten carbide via the oral route is limited when compared to sodium tungstate. Therefore, the read-across from sodium tungstate (source substance) to tungsten carbide (target substance) is an appropriate conservative read-across approach for systemic toxicity. For details on the tungstate read across approach category refer to Annex I.
No need for a Cohort 3 is needed based on two (developmental) immunotoxicity studies (Fastje et al. 2012;Osterburg et al. 2014)that exposed mice to tungstateinutero. Both studies were included in the tungsten trioxide submission. An adaptio nforAnnex X, Section8.7.3.; test method: EU B.56./OECD TG 443– Cohort 3 is been requested based on these two studies.Fastje et al. (2012) and Osterburg et al. (2014) studies were submitted in the tungsten trioxide registration. At this time, we are presenting more details on the study design and results to support our recommendation that a Cohort 3 is not justified.To determine if sodium tungstate can cause an unnatural immune response, mice were exposed in utero by parental inhalation or ingestion of an estimated dose of 1 and 4 mg/kg bw/day, respectively; and inoculated with respiratory syncytial virus (RSV) (within 2 weeks of weaning). The dams were exposed to sodium tungstate through water (15 ppm,ad libetum) and aerosol. During the 45-min, 5 days/week aerosol exposures, female mice were exposed to a 187 g/L solution nose-only for 1 week prior to conception and 3 weeks of gestation until parturition halted exposures.Pups were weaned on to tungstate-spiked water (15 ppm,ad libetum). At 21–35 days of age the mouse pups were lightly anesthetized and the nasal cavity inoculated with human RSV.Peripheral hematology was evaluated utilizing complete blood counts.Spleen tissue was massed and splenic ratio calculated as spleen mass per body mass. Results showed that controls and tungstate only-treated mice did not exhibit pathological indicators. RSV inoculation within 2 weeks of weaning was associated with a neutrophil shift. When the RSV inoculation was combined with exposure to tungstate(Na2WO4+ RSV), significant splenomegaly resulted in addition to other hematological pathologies which were not significant Exposure to Na2WO4+ RSV resulted in hematological/immunological disease, the nature of which wasinconclusive (Fastje et al. 2012). Osterburg et al. (2014) tested if exposure to sodium tungstate can result in an immune effect in a one-generation (one-gen) model and intraperitoneally injected with Staphylococcal enterotoxin (SEB). For this, parental male and female mice were orally exposed (via drinking water) to 0, 2, 62.5, 125, 200 mg sodium tungstate/kg bw/day.Both P and F1 micewere maintained on these doses for the course of the study. These tungstatedoseswere selected based onprevious workbyMcInturf et al.(2011) that used similar doses in rats. Mice were exposed to tungstate for 90-days prior to mating (Weeks 1–12). The next 7 weeks comprised gestation and weaning (Weeks 13–19). After pups (F1)were weaned, the parents (P) were necropsied, approximately19 weeks after initiation of the study. The F1 generation was exposed to tungstate for a further 90-days after weaning and then necropsied. Mice were housed singly during the course of thestudy and pair mated for breeding. After confirmation ofpregnancy, males were removed. During all phases of the one-gen study mice were kept on the appropriate tungstate dose (Osterburg et al. 2014). Results showed no statistically significant changes in bodyweight due to any tungstate dose levels.The 200 mg/kg bw/day males in the P generation show a consistenttrend towards decreased weights(Osterburg et al. 2014). Complete blood counts and hematological parameters from theblood of animals at necropsywere performed. With two exceptions (monocyte%and red blood cell distribution width), there were no statisticaldifferences in the data between P and F1(Figure 2). No significant changes in any of the parameters measured in response to tungstate, except for the percent monocytes. There were fewer lymphocytes in the F1 generation compared to the P generation (p<0.023), but this was not dose-related. Additionally, the red blood cell distribution width (RDW) was higher in the P generation vs the F1 pups(p<0.004). The percentage of monocytes was dose-dependently lower at higher concentrations when compared to control (p<0.003). Other parameters suggest a dose-dependent trend (e.g. hematocrit); however, these trends were not statistically significant(Osterburg et al. 2014). Tungstate-dependent changes were only observed in the spleens of animals. Furthermore, any statistically significant differences between the innate or immune responses of P and F1 mice were not noted. One-gen tungstate exposures resulted in reduced quantities of CD71+TH cells in theP and F1 mice for the 200 mg/kg/day dose group compared to the control groups.No statistically significant differences were noted in the overall quantity of CD3+CD4+TH cells. Were no statistically significant differences in quantities of CD3+CD8+cells. The cytotoxicCD3+CD8+CD71+cells in theP and F1 mice were decreased inSEB-challenged groups in 200 mg/kg/day group (Osterburg et al. 2014). Among cytokines measured in plasma, the only significant change was a dose-dependent quantitative decrease in interferon IFNγ levels in SEB-treated mice. Although not statistically significant, the F1 mice had an overall reduced IFNγ response, especially at the 62.5 mg/kg/day dose, compared to their parents (Osterburg et al. 2014). Overall, an immune response was confirmed by two separate in utero exposure studies when tungstate is co-exposed with an immune-stimulating agent such as RSV (Fastje et al. 2012) or SEB (Osterburg et al. 2014). When tungstate was co-exposed with an immune-stimulating agent an enlarge spleen or immunosuppression can be observed. This modulation of the normal cell-mediated immune response was also confirmed on two 28-day oral adult mice drinking water studies at similar sodium tungstate doses which co-exposed tungstate with SEB (Osterburg et al. 2014) or to P815 mastocytoma cellsex vivo, prior to functional assessment in the effector phase(Frawley et al. 2016; US NTP 2012). ECHA's draft response also indicates a concern on delayed-type hypersensitivity (DTH) response in developing animals based on an adult study (Osterburg et al. 2014). However, on a separate study(Frawley et al. 2016; US NTP 2012) the DHT response is not observed making this effect equivocal. The available DHT studies are discussed below. Osterburg et al. (2014) exposed mice to tungstate orally at doses (0, 0.2, 2, 20, 200 mg/kg/day) in their drinking water for 28-days. Animals were sensitized to the chemical 4-Hydroxy-3-nitrophenyl acetic acid active ester (NP-O-Su) by subcutaneous injection. During the sensitization phase, appropriate tungstate doses continued to be administered to the treated mice.Ten days later, the mice were challenge into the right hind foot pad and the extent of footpad swelling was measured 24 -h post-injection. Results showed that the 200 mg/kgbw/day group resulted in significantly less swelling in the NP-O-Su challenged footpads. In the first experiment (DTH 1), both the 20 and 200 mg/kgbw/day dosed hosts had less edema than the saline. In a subsequent series (DTH 2), it was again found that there was significantly reduced swelling because of the 200 mg tungstate/kgbw/day treatment. However, at two lower doses (2 and 0.2 mg/kgbw/day), significantly reduced swelling comparedto control mice that had not been exposed to tungstate was not observed. In the US NTP immunotoxity study no effects were observed on thein vivo DTH response to Candida albicans (Frawley et al. 2016; US NTP 2012). Briefly, female mice were exposed to sodium tungstate via the drinking water at 125,250, 500, 1000, or 2000 mg/L (estimated oral doses of 30, 60, 120, 240, and 480 mg/kg bw/day) for 28-days. Mice were immunized with C. albicans by subcutaneous injection on Day 21 and challenged on Day 29 with the C.albicans antigen chitosan in the right footpad. Footpad swelling measured prior to challenge and 24-h post-challenge. Footpad swelling was calculated as [(post-measurement – premeasurement)100] and reported in terms of mm 100. A challenge only group, which received the chitosan injection on Day 29 without prior immunization with C. albicans, was included to control for non-specific footpad swelling. Results showed that no effects were observed on the delayed-type hypersensitivity response to C. albicans (Frawley et al. 2016; US NTP 2012).
Conclusion: There is sufficient (developmental) immunotoxicity and on adult mice immune system evidence that demonstrate that tungstate (the tungsten ion bioavailable at physiological conditions) causes at 200 mg/kgbw/day a modulation of the normal cell-mediated immune response only when tungstate is co-exposed with an immune-stimulating agent (such as RSV, SEB, or P815 mastocytoma cells). In addition, a concern of effects on the DHT of developing animals is based on equivocal adult immunotoxicity studies. Based on the weight of evidence, the addition of Cohort 3 in a potential EOGRT study is not justified.
No immunotoxicity studies are available for tungsten carbide. However, data were available on sodium tungstate, which were used for read-across. Sodium tungstate did not affect innate immunity, humoral immunity, or on developing hematopoietic cells in the bone marrow, and on unstimulated splenocyte phenotypes in female B6C3F1/N mice exposed via the drinking water. In addition, sodium tungstate did not adversely affect immune-organs of mice (thymus, spleen, mesenteric lymph node, popliteal lymph node, mucosa-associated lymphoid tissues, or bone marrow) and rats (McInturf et al, 2011). As potential cell-mediated immune effects are only observed under conditions of co-exposure to an immune-stimulating agent rather than direct action.Therefore, tungsten carbide is not considered a direct immunotoxicant, and based on the lack of direct immunotoxicity effects observed, no classification is warranted.


to achieve an average 80% load on each generator set.
The minimum load that the generator set should be operated at is 25% to 30% of its rated capacity.
every 300 hours of generator set operation.
capacity of the generator sets that are being paralleled, the generators will overload and the TQG could be damaged.
match voltage requirements of load (WP 0006, Table 1).
Notify maintenance to change Reconnection Board and to reprogram the GSC and DVR to obtain required output.
with a 100 kW TQG, designate the 200 kW TQG as No. 1.
Verify that generator sets are grounded. Ground each generator set (WP 0006 00-2).
Common ground should be used.


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Kim Kardashian on Kanye West's mental health, letting go of 'anxiety' over his Trump support
Taryn Ryder
·Writer, Yahoo Entertainment
American television and social media personality
American rapper
Kim Kardashian is opening up about Kanye West's mental health like never before.
In her Vogue profile, the KKW Beauty mogul was not only willing, but eager — according to her publicist — to address her husband's mental issues that have played out in front of the world. (In 2016, he was hospitalized for a "psychiatric emergency" and just last year made headlines for various controversial statements and outbursts.)
Kanye West and Kim Kardashian West attend the Versace fall 2019 fashion show on December 02, 2018 in New York City. (Photo: Roy Rochlin/Getty Images)
When meeting with President Trump in October, West denied he was bipolar just months after revealing the diagnosis, declaring he was suffering from sleep deprivation instead. According to the Keeping Up With the Kardashians star, West has once again accepted he's bipolar, but noted there were conflicting assessments from doctors.
"I think we're in a pretty good place with it now," she declared, explaining that West hopes to show the world you can live a normal life with mental illness. "It is an emotional process, for sure. Right now everything is really calm. But we can definitely feel episodes coming, and we know how to handle them."
The rapper has made it clear he does not like to be medicated and it's something Kardashian has accepted.
"For him, being on medication is not really an option, because it just changes who he is," she stated. "Traveling a lot does set it off, so he doesn't travel as much as he used to."
The reality star (and aspiring lawyer) also had something to say to those people who have criticized her for not intervening or doing enough before West's public outbursts.
"But honestly, I never want to speak for him, because I am not in his mind. But I think some of the hurtful things that I read online . . . . What is she doing? She's not stopping him. . . . Like it's my fault if he does or says something that they don't agree with? That's my husband," she fired back. "I share every opinion that I have and let him know when I think something's wrong. Or if it comes to him being in the middle of a bipolar episode, I'll do everything to be supportive and help to calm the situation."
Many of West's headline-grabbing antics last year had to do with his support of Trump, but Kardashian insisted he doesn't identify as Republican or Democrat.
"He doesn't represent either side. But he doesn't want to be told what he should be," she said. "It can be confusing. I get it."
But Kardashian did cop to getting stressed over his love for that Make America Great Again hat. (She publicly supported Hillary Clinton during the 2016 presidential election.)
"The one thing that I respect so much is that he is who he is, no matter what anyone tries to tell him to do. I can be sitting there crying: OH, MY GOD! TAKE OFF THE RED HAT!" she added. "Because he really is the sweetest person with the biggest heart."
Kardashian continued, "I stopped caring, though. Because I used to care so much. I was making it such an issue in our relationship. And in my life. It gave me so much anxiety."
West has kept a low-profile on social media in recent months, but is emerging back into the spotlight. He is appearing more than he ever has on the new season of Keeping Up With the Kardashians; however, it's unclear if he or the Kardashians will address his mental health issues on-air.
Read more on Yahoo Entertainment:
Blake Shelton 'absolutely destroyed' over country singer Earl Thomas Conley's death
Jennifer Lopez denies Alex Rodriguez cheated: 'I know what the truth is'
Bryan Cranston reacts to being a 'villain' in a bizarre Trump campaign video: 'I seem to have a high disapproval rating'
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Q: Book where a boy with tattoos is destined to defeat an evil demon The book cover has a man with a yin yang tattoo on his shoulder and a dragon tattoo on his arm. His back is facing the front and in the background I believe there is a mountain or valley.
The story is about a boy with these tattoos who is destined to defeat an evil demon who was sealed away in a mountain. He comes into contact with a monkey whose duty is to train the boy to fight the demon.
While this is going on, his mother meets a monk while traveling on the road, and they end up falling in love. However at the end of the book she is kidnapped I believe by a demon of something like that and the monk has to go rescue her.
Please help me to identify the book, this is all I remember about the story but I was hoping that by now the sequel would have come out by now. But I can't remember the title! I read the book about three years ago, but I know it came out years before I read it. I believe it came out in the early 2000's and is a Chinese myth/folk tale type book

A: I believe you are looking for The Outlaws of Moonshadow Marsh - The Sign of Qin.
The cover does depict a tattooed boy with a dragon on his left arm, facing away towards a mountain surrounded by clouds. The boy is born with the sign of an outlaw, and is destined for death by his Emperor father. However, he is foiled by a monk and a trickster monkey. Additionally, just before his birth, a volcanic eruption looses a bunch of trapped demons.
He doesn't have a yin/yang symbol, but he does have a white circle with what looks like a small black sword, that could be mis-remembered as a yin/yang.
It was published in 2006, but unfortunately it doesn't look like book #2 or #3 was ever published.

A: I remember this book, I vaguely remember it being called something like "The Monk With 1,000 Tattoos" or something like that. 6 years later lol

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REZZ has been spending a lot of time recently mastering her art, and this EP seems to prove that hard work does indeed pay off. The artist hailed the EP as "darker and heavier than ever before" and a piece of work that she's most proud of thus far in her career. She's created a staple sound that draws from influences ranging everywhere from Marilyn Manson to Gesaffelstein. The sound is heavy, dark, eerie, chill-sending techno with industrial rock influences. I cannot wait to see where 2016 takes this talented young producer, BIG ups to one of the most talented females in the industry.


The concept of virtual power plants, established by networking domestic solar array batteries, is one which is becoming more popular with communities. Researchers are looking into how this can work, and one trial is happening on Bruny Island, Tasmania, overseen by Associate Professor Evan Franklin. Barry Mitchell spoke to Dr Franklin about this trial, and about the future for virtual power plants.


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Not a Yes, Means a No: Spanish Laws Roar For Change
Date: February 13, 2020Author: manulawskills 5 Comments
Sexual offences against women have often been termed as a "silent epidemic" [1] mainly due to the propensity of such cases going unreported. It is only in the recent years that women globally have broken the long imposed societal omerta of keeping quiet over the sexual offences committed against them and have openly started confronting their offenders with popular and effective movements like the MeToo Movement (amongst other forms of their expression) being the glaring instance. These movements have not only given voice to the long-suppressed other gender against their offenders but have shook the conscience of the society globally at large in one way or the other. While the global society together strives towards making the world a safer and equal place for women, there happen instances or incidents time and again which makes one question the advancements our societies have made to this end. While at times these incidents relate to the complete neglect or apathy shown by the society towards the critical nature of sexual offences, the other times these incidents show the inefficiency or loopholes in laws of various nations in dealing with sexual offences.
The Manresa Incident and the Judgment of the Court
A recent incident highlighting the lacunae in law dealing with the offence of rape and thereby inviting irk of the people from every stable of the society in Spain was the judgment of a Barcelona Court in a case involving the rape of a 14 year old girl in Barcelona.[2] The Court in its judgment while interpreting the Spanish Laws with respect to the offence of rape or sexual assault (as it is called in Spanish Law) held five men accused of gang-raping a girl to be only guilty of the lesser offence of sexual abuse and not sexual assault. The judgment of the court was rooted in the fact that the victim was unconscious under the effect of alcohol and thus could not either consent to or oppose the sexual advance. [3] Thus, the necessary element of the use of violence or intimidation as necessary under the Spanish laws to constitute the offence the rape was found to be missing on account of the victim's inability to either consent to or oppose the act.
A Brief Analysis of Spanish Laws with Respect to the Offence of Rape
The Spanish Criminal Code,[4]which is the penal law operational in Spain defines the offence of rape as a situation where the sexual assault consists of vaginal, anal or oral penetration or inserting body parts or objects into either of the former twp orifices.[5] Thus, in order to understand the meanings and contours of this definition, one has to look at the definition of sexual assault in the Spanish Criminal law as the very meaning and definition of rape is contingent on whether an offence can be classified as sexual assault in the first place itself. Sexual assault under the Spanish criminal law is defined as offending the sexual freedom of another person through the use of violence or intimidation. [6] Thus, on an analysis of these provisions of the Spanish Criminal Code it becomes crystal clear that the use of violence or intimidation by the Accused is necessary to constitute the offence of sexual assault and thereby to constitute the offence of rape.
However, on a closer analysis of these provisions of the Spanish Criminal Law it becomes very clear that there is a complete ignorance or disdain towards the importance of consent in Spanish Criminal Laws with respect to the offence of sexual assault. Consent under the Spanish Criminal Law is not the primary fulcrum on which the offence of rape is dependent upon but a mere derivation from the presence or absence of intimidation or violence in the commission of the offence of sexual assault. Thus, in cases such as the Manresa Rape Case, though the modesty of a women was outraged in the absence of her consent, no offence of rape could be made out as per the law since due to inebriated and unconscious status of the victim, the Accused did not have had to make any use of violence or intimidation for the commission of the offence. What the Spanish law ironically requires is a heroic fight back from the victim in cases of sexual assault with consent not being the consideration to constitute the offence of rape.
Laws in Other European Nations with Respect to the Offence of Rape: Consent Based v. Physical Violence Based
The European society at large has often been seen as a beacon of advancement and equality especially when it comes to women and their rights. However, when one looks upon the laws prevalent in a number of European Nations with respect to sexual assault/rape this prospective of the European Society stands under questionable docks. Only 8 out of the 31 nations in the European Economic Area (Sweden, The United Kingdoms, Ireland, Luxemburg, Germany, Cyprus, Iceland and Belgium), [7] and Switzerland, [8] have consent-based rape legislations in operation. In other European Nations such as Spain, France, Greece, Italy etc. to only name a few amongst the rest of the 23 countries, the meaning of rape still depends upon the use of force and not that on the presence or absence of the consent of the victim. [9] As per a 2014 report of the European Agency for Fundamental Rights [10] around 9 million women in the European Union have suffered from rape since the age of 15. In Denmark alone (one of the nations where the definition of rape in penal laws is not based on consent), around 24000 women experienced rape or attempt to rape in the year 2017 itself [11]. However, with respect to Denmark and in general with the nations where the definition of rape is not consent-based is the shockingly low number of convictions when matched against the number of cases or instances of rape or an attempt to rape (against 24000 cases the number of convictions in Denmark in 2017 stood at a meager 94).
What Spain Can Learn from Other Nations?
Spain and other nations where the definition of rape is not consent-based can learn from their few European counterparts under the laws of which, the element of consent and not that of violence or force is the necessary element for constituting the offence of rape. In the United Kingdom, a person is said to have committed the offence of rape if they intentionally penetrate the vagina, anus or mouth of another person with their penis without the consent of the latter [12]. This legislation takes a step forward to define consent with respect to rape and other non-consensual offences by providing that a person consents if he/she "agrees by choice, and has the freedom and capacity to make that choice."[13]. The European Court on Human Rights while deciding the case of M.C. v. Bulgaria[14] has also held that lack of consent and not proof of resistance from the survivor is the determinative factor for the establishment of the offense of rape. Absence of consent is the determinative factor in establishing the offence of rape even under the Indian Penal Code. [15]
Spain and The Istanbul Convention
Spain, amongst other European Nations is also a signatory to the Istanbul Convention, [16] which requires criminalisation of rape and all other non-consensual acts of sexual nature. [17] Further, Spain has also ratified the Istanbul Convention which obliges its signatories to make laws with respect to violence on women in line with Convention itself. The convention itself stipulates sex without consent to amount to rape. [18] Thus, it is imperative that the law makers in Spain do not waste any more time towards making the required amendments to the Spanish Criminal Code so that another victim does not suffer the same fate as that of the Manresa incident at the hands of the law which completely invalidate the importance of consent with respect to a crime as heinous as sexual assault/rape.
The Manresa Rape Case adds to the pile of cases wherein the Accused is awarded a lesser punishment than what would be justified. After the addition of another disgraceful feather in the government's hat, it's high time to overhaul the patriarchal laws of Madrid, and give women their long denied due justice. Having 48 UNESCO World Cultural Heritage sights on the map, [19] it is but imperative that a nation like Spain needs to enact legislations at the earliest so as to check the recent trend of people accused of rape getting punished for lesser crimes due to the absence of the concept of consent with respect to the offence of rape in the criminal laws of the country. The protest on the streets of Madrid speaks of the need to acknowledge the forgotten concept of consent, a concept missing in the Spanish Rape Laws. Living in an age where sexual offences are being considered as one of the most heinous crimes, crimes against humanity, it is imperative that the perpetrators of such acts do not dodge their fate. The recent rise in reported incidents of sexual abuse, validate the mounting trust of the public on the judiciary. However, with slack laws on sexual offences, the confidence is fading away, and the audacity of the sinners is on an upsurge. History repeated itself as we see a reflection of the recent Wolf Pack Case [20], where the Accused were not punished for the offence of rape by a Lower Court in Spain as the victim was unable to offer resistance under the influence of alcohol, in the Manresa Case. And so, will it again if the laws are not reformed.
[1] Antonia Abbey, Tina Zawacki, M.A., Philip O. Buck, M.A., A. Monique Clinton, M.A., and Pam McAuslan, Alcohol and Sexual Assault, Alcohol Research & Health. 2001;25(1): 43-51, https://pubs.niaaa.nih.gov/publications/arh25-1/43-51.html
[2] Harrison Jones, Outrage as five men are acquitted of gang raping unconscious girl, 14, in Spain, Metro News, November 1, 2019, https://metro.co.uk/2019/11/01/outrage-as-five-men-are-acquitted-of-gang-raping-unconscious-girl-14-in-spain-11025755/
[3] Oz Katerji, Five men are acquitted of gang rape in Spain after court rules no force was used because the 14-year-old victim was unconscious, The Daily Mail, November 1, 2019, https://www.dailymail.co.uk/news/article-7638517/A-Spanish-court-acquitted-five-men-gang-raping-14-year-old-girl-unconscious.html
[4] Criminal Code of the Kingdom of Spain, 1995 (The Kingdom of Spain).
[5] Article 179, Criminal Code of the Kingdom of Spain, 1995 (The Kingdom of Spain).
[7] Peter Rook QC and Kirsty Brimelow QC, An expert view: Why most European countries still need to change their rape laws, Amnesty International, March 7, 2019, https://www.amnesty.org/en/latest/news/2019/03/an-expert-view-why-most-european-countries-still-need-to-change-their-rape-laws/.
[8] Anna Błuś, Sex without consent is rape. So why do only eight European countries recognise this?, Amnesty International, April 23, 2018, https://www.amnesty.org/en/latest/campaigns/2018/04/eu-sex-without-consent-is-rape/.
[9] Right To Be Free From Rape Overview Of Legislation And State Of Play In Europe And International Human Rights Standards, Amnesty International, November 24, 2018, https://www.amnesty.org/download/Documents/EUR0194522018ENGLISH.PDF.
[10] Violence Against Women: an EU wide survey, European Agency for Fundamental Rights, March, 2014.
[11] Laura Deen, Kathrine Bindesbøl Holm Johansen, SannePaghMøller, Bjarne Laursen, 'Violence and sexual abuse', 2018, p.52, http://www.sdu.dk/da/sif/rapporter/2018/vold_og_seksuelle_kraenkelser., retrieved from :Give Us Respect And Justice!" Overcoming Barriers To Justice For Women Rape Survivors In Denmark, Amnesty International, https://www.amnesty.org/download/Documents/EUR1897842019ENGLISH.PDF.
[12] §1, Rape and Sexual Offences- Chapter 2, Sexual Offences Act, 2003 (The United Kingdoms).
[13] §74, Rape and Sexual Offences- Chapter 3: Consent Sexual Offences Act, 2003 (The United Kingdoms).
[14] M.C. v. Bulgaria, No. 39279/98, ECHR 2203XII (The European Court on Human Rights).
[15] § 375, The Indian Penal Code, 1862 (The Union of India).
[16] Convention on preventing and combating violence against women and domestic violence, 2014 (The Council of Europe).
[17] Article 36.1, Convention on preventing and combating violence against women and domestic violence, 2014 (The Council of Europe).
[18] Ivana Kottasova, Five men acquitted of rape because unconscious teenage victim didn't fight back, CNN, November 1, 2019, https://edition.cnn.com/2019/11/01/europe/barcelona-rape-sexual-assault-intl/index.html.
[19] Spain: UNESCO World Heritage Sites, https://whc.unesco.org/en/statesparties/es.
[20] Spanish court acquits 5 men of rape on grounds that 14-year-old victim was unconscious, CBS NEWS, November 1, 2019, https://www.cbsnews.com/news/spain-rape-trial-5-men-acquitted-today-on-grounds-that-14-year-old-victim-was-unconscious-2019-11-01/.
The article has been written by Akash Anurag and Navya Bhandari
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Congrats Wilbur for proving that it ain't over until it's over, this is one of 4 caught yesterday in the river. For me, Seafood Festival tonight, then off to CR for some tarpon payback.....planning on getting on my tuna as well as some sailfish, it's been really good down there.
Great topwater bite this morning and this afternoon as reported by Capt. Greg. Capt. Joe is on such a good trout bite that I have hired him for tomorrow!!
Nice heavy handful of 19-22 inch flounders like this one, also decent trout and a little pup. Nice day in the rain.....unlike the flounder on this pretty day, no need for sunglasses today.
.....until late this afternoon....geeze, too much time on the couch. Newsletter about to go out.
In Costa Rica they had a good half day with the dolphins, catching a couple heavy handfuls.
So you're afraid to get a little wet?
Buy a rain jacket......although it is just cheaper to cancel your two day charter.
Open tomorrow if anyone out there isn't so sweet that they're afraid that they're going to melt.
Some nice flounder for us yesterday and a couple big drum. It was Capt. Brian's last afternoon on the water and he finished with a bang with a double digit afternoon on the big 'uns.
plus a handful of 18-21 inch flounder and a couple pups.
With extreme conditions, you never know if it's going to be 18 inches or 48 inches.....in this case, over 50 inches.
The guys who fished today had a decent day, catching handfuls of big 'uns and double handfuls of keepers.
Keep an eye out for our upcoming newsletter, working on that this week. We'll have some details on openings on our TARPON catching trip in Costa Rica Oct. 5-9. Also our inaugrial BONEFISH/PERMIT trip to Belize Dec. 10-17.
Just talked to Capt. Brian and Capt. Gary, both of those guys have at least a handful of big 'uns this morning. With winds more out of the north, they've got some calmer water to fish.
This is one heck of a nor'easter, some of the roughest conditions that we've fished in, the only thing missing with this storm is a name. But as predicted, some big drum got pushed up the river. It ain't over yet..... Decent fishing for the pups and yearlings on the shoreline on Friday with a handful of big ones. Today was not as good along the marsh, but some of the guys had double handfuls of big drum as far up the river as Oriental..... We caught a few today, but conditions were so rough, wet and cold, we bagged the trip and came in early for a hot shower.
So what's going on with the fish?
Ten years ago, when I met Anna, she was working on her masters degree in marine science. She hired me and some of the other Down East Guides to help deploy her hydrophones which would record the courtship calls of red drum.....and many other fishes, but it was red drum that was her focus. Only the male drum make the drumming noise with muscles along their swim bladder and they only spawn at night, starting about sunset and winding down by midnight.
The hydrophones had to be set up before sunset and they had to be picked up by dawn so she could download the data, charge the batteries and get them ready to go back out in the afternoon. Anna was recording drum calls for 3 summers.
Drumming drum were recorded throughout the Pamlico Sound, lower Neuse and Pamlico Rivers. Spawning calls were recorded in late July, with peak activity occurring in August and September. There also seemed to be a peak of spawning during the full/new moons, but not enough years for this observation to be statistically significant. By late September, nearly all of the females had spawned out. During the last full moon in September or the first full moon of October most of the drum quickly left the sound.
So what's going on this year? The full moon was in early September, on Sept. 13 and fishing has been tough the past few days. Why?
1) The full moon factor: I've always said that the best fishing that I've ever had (tarpon, sailfish and drum) has been on the full moon.......and the worst days that I've ever had have been on the full moon. If you are there when they are biting, it's "epic", but they only seem to bite for a few hours each day. If you aren't there when it's happening, it ain't happening.
2) The spawn: With the big drum, the full moon factor can be compounded because they are activlely spawning and have something else on their mind than feeding.
3) Elvis has left the building: The big migration out of the sound is usually on the last full moon in September/early October, but the September full moon was a few days ago. Last week we started seeing many drum that have spawned-out, but also many drum that are still very gravid and far from finished. I believe that a lot of the fish that have already spawned chose this moon to exit the sound. Two days ago there was a large school of drum seen heading out of Drum Inlet. At about the same time, large schools of tarpon were seen between Cape Lookout and Beaufort....heading South.
4) Hurricane water: Before the storm, the best fishing was upstream of Oriental. After the storm, we had the best drum fishing ever, but each day we have seen the biggest body of fish slide down the river towards the sound, staying ahead of the dark, fresher water from upstream.
So what's the forecast? Getting better.
The full moon factor is subsiding each day, so fishing is going to improve, and fishing did get much better for me yesterday, we had a double digit afternoon. We are still catching a lot of fish that have not spawned out, so these fish should be around for a while. Although a lot of fish pushed into the sound or beyond from the fresh water, this nor'easter is going to turn things around. It's supposed to blow out of the NE for the next couple of days, which always makes for good drum fishing. It's going to mix up the water and shove a lot of saltwater up the river, with it will come the drum that are still out there.
I couldn't believe that Seth offered up the rod on the first couple of fish to his dad and Mike.....he got his turn, but it was late in the day and the fat lady was warming up in the background. Seth proving that the fish he just caught is almost as big as he is.
Ha, ha not here. I got a report of large schools migrating south....in the ocean between Cape Lookout and Beaufort Inlet yesterday....don't know where they were coming from, I haven't seen much of them this summer. If you want to get into some tarpon catching instead of tarpon fishing, we have some discounted openings as a result of a last minute cancellation on our annual tarpon fishing trip to Costa Rica.
We also have a couple of groups looking for singles or pairs to split their sailfish trip in January and in March.
Capt. Gary had a good morning light tackle fishing up the Neuse today, PLENTY of stripers on top water once he got below the bad water up around New Bern. That should clear out over the next few weeks. He finished the afternoon with a couple of heavy handfuls of big drum.
Capt. Brian had another big day with "Never Enough"....catching just enough to make him happy.
I had the pleasure of sleeping late and taking the Vice-Chairwoman of the Marine Fisheries Commission and a couple of her friends out for an afternoon of drum fishing....everyone got a couple of fish, including some big enough for their citations.
Mixed reports from the guys today, fortunatly we found some that were biting this morning, catching a few heavy handfuls in 4 different locations, including a school of busting fish that we were able to sight cast and hook a couple on bucktails......until someone rode through the school as we were hooked up......some people don't have a clue. For others, the bite was tough and reports were mixed, some folks had good flurries while others spent a lot of time waiting. They are spawning hard during the night with a good morning bite and laying up and recovering for much of the day. As we move away from this moon, the bite will pick up.
While the Down East Guides were getting what they needed, Capt. Brian and I went on a mission, leap frogging from Oriental to Ocracoke until we found what we needed. Good fishing for everyone.
Debris has pretty much cleared, but fishing is more....."challenging"....everyone is still catching plenty of fish with a lot of double digit half days. We're getting what we need, but the "big body" has moved around a bit with a lot of brackish, stained water coming downstream.
An inshore grand slam anyway. My 3 guys yesterday made their first trip to the Pamlico Sound and at the end of the day each of them had a fist full of citation drum, plus several just under 40 inches. Fishing with me again this morning, they asked, "Is there anything else out there to catch?" I guess we got 'em too good yesterday afternoon. With a livewell full of finger mullet, each of them caught keeper trout, nice flounder and some in the slot pups......that are now on their way to the mountains. It was good to see the mixed bag, haven't done much of that in a while.
"George: Good to see you on the water Saturday afternoon. I am emailing just to say thanks for making my fishing experiences with you both fun and informative. I took my two sons ages 14 and 11 after the old drum on Saturday night. My wife was there as well with the video camera and also a regular camera. We caught 6. I reeled in zero and had the best time fishing that I have ever had. I learned enough with you and Greg over the years to have a chance when I go and how to do the right thing by the old drum.------Walter"
Anyone leave a small blue bag in the console of my boat?
..... unequivocably belongs to Capt. Brian Harrington, Jim "Never Enough" and John "The Great One". Congratulations guys.
No dove hunting for me tomorrow......and no records......I'll be very happy with going out with Anna as the "mate" and catching a citation or two for my customers, maybe that will be a record for them.
Here's a pic of one of the "toads" that Capt. Gary recently caught. On my way home yesterday it looked like Capt. Gary was very busy with the afternoon bite.


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text:
Chua Jui Meng should tender a full apology for misleading Parliament and the nation on Anwar's health and German specialist Dr. Thomas Hoogland
(Petaling Jaya, Wednesday): Health Minister, Datuk Chua Jui Meng should tender a full apology for giving an untrue answer in Parliament yesterday about the health of former Deputy Prime Minister, Datuk Seri Anwar Ibrahim and German specialist Dr. Thomas Hoogland.
Chua told Parliament that he had surfed the Internet and said: "Although Dr. Hoogland claims to be an expert in endoscopic surgery, we cannot find any literature written by him on the Internet nor any of his publications on international medical journals." (The Star)
Chua even said that Hoogland may not be a spine specialist claiming that extensive searches on the Internet and medical journals dating back five years showed no evidence of Hoogland's expertise. (The Sun).
I am shocked by such irresponsible statement by Chua, as during the controversy over Anwar's health condition, I had last month visited the website of the Alpha Klinik in Munich, Germany, which "specialises in minimal invasive knee and spine surgery" where Hoogland is the Director of the Back Unit -
http://www.alphaklinik.com/
I distinctly remembered reading materials about Hoogland's expertise as a specialist, and this has again been confirmed when I visited the website again.
Before helping to found the Alpha Klinik in 1989, Hoogland was Staff Orthopaedic Surgeon and Chief of the Residency Program in Ignatious Hospital in Breda, the Netherlands for a number of years. He graduated as a doctor from the University of Groningen in the Netherlands in 1972. From 1973 to 1978 he trained as an orthopaedic surgeon at Cleveland Clinic in the U.S. and received his American Orthopaedic Board Certification. From 1978 to 1980 he was Staff Surgeon at the University Hospital of Groningen.
Hoogland had performed over 8000 - including over 6000 minimal invasive spine operations - during his career as a surgeon. In addition, he had published 22 scientific papers, contributed to four books and spoken at over a hundred congresses (including organising a number of them).
In addition, he was a member of The German Society for Orthopaedics and Traumatology, The American Academy of Orthopaedic Surgeons, The North American Spine Society, The Scientific Society for Spinal Microsurgery (of which I am President), The International Society for Minimal Intervention Spine Surgery and The Society for Spine Surgery Research.
I have not done any extensive search on the Internet, but a quick search turned up a reference to an article by Hoogland in the April 1999 issue of SPINE (Volume: 24, Number 8):
"Wilke, H.J., Neef, P., Caimi, M., Hoogland, T., and Claes. L.E. (1999) New In Vivo Measurements of Pressures in the Intervertebral Disc in Daily Life, Spine, 24 (8), 755-762".
How then can Chua claim that "extensive searches on the Internet and medical journals dating back five years showed no evidence of Hoogland's expertise".
Chua should apologise publicly for misleading Parliament and the nation on Anwar's health and Hoogland.


Established in 1956, the proven thoroughbred nursery, White Robe Lodge, has 660 acres in total. The main farm is situated at the northern end of the Taieri Plains and enjoys a unique climate, sheltered by the surrounding hills to the North and East. The middle farm, Ardgowan, lies 5 km to the west. Our wintering farm is in Middlemarch and has proven to be a valuable asset to our operation.
We are a family orientated business and our Breeding and Training operations are run by family members. Founder Brian Anderton is a long time servant of the New Zealand Thoroughbred Industry. He received a New Zealand award for outstanding contribution to racing excellence in 1993 and he was inducted to the New Zealand Racing Hall of Fame in 2012.
In it's time, White Robe Lodge stood two Australasian champion sires, Mellay and Noble Bijou. The names of these two sires lives on in their daughters, who have continued to produce top class racehorses. Noble Bijou is the only sire in the history of New Zealand Thoroughbred Breeding to have won both the general and broodmare sires list in the same year.
After 60 years in the thoroughbred business, White Robe Lodge continues to produce top class racehorses.


Mexicans and African Americans combine to make up a huge percentage of the population in the US, and a majority (56%) here in Chicago. Bringing these two groups together could result in important social changes that could take the shape of anything that is meaningful to both groups, from reforming the public education system to electing the next president. This has occurred already in Chicago with the election of Mayor Harold Washington and in Los Angeles with Mayor Antonio Villaraigosa. However, before this can happen on a larger scale, the groups must feel solidarity with one another, a sense of empathy that springs from having a common purpose.
Participating in another's struggle means making it your own. One of the things that can inform such collaboration is history. Knowledge of a shared history counteracts the ignorance and fear of others that combine to create prejudice. In turn, this knowledge can generate solidarity, which can encourage action.
As curator of museum exhibitions, I am in the business of disseminating information and ideas that can foster collaboration and solidarity. I work for the Mexican Fine Arts Center Museum (mfacm) and I curated one of the exhibitions that was on view this past spring and summer, Who Are We Now? Roots, Resistance, and Recognition.
Who Are We Now? was part of the larger project, The African Presence in M\xe9xico, which consisted of three exhibitions, more than 20 public programs, a catalog, and an eight-unit curriculum. Another exhibition in the project, From Yanga to the Present, told the story of people of African descent in Mexico over the past 500 years and explained how the Afro-Mexican population became virtually invisible in Mexico. In fact, the long and rich history of African presence in Mexico should be incorporated into elementary school education in Mexico and the US, especially since it has the potential to bring together two often disparate groups.
My exhibition, Who Are We Now?, is the one people walked into after seeing The African Presence in M\xe9xico. The intention was that people would learn about the connection between Africans and Mexicans, and then bring that information home to bear on their experiences in the US.
Who Are We Now? dealt with the relationships between Mexicans and African Americans in the US and between African Americans and the country of Mexico. Since people in the US tend to think that these two groups don't or can't get along, I set out to tell the history of collaboration between them, which is substantial and not well known. My hope was to take a step towards bringing people together, making a true majority out of two so-called "minorities." If Mexicans and African Americans who saw the exhibitions left the Museum either feeling related in some way, or simply feeling more informed about each other, then the exhibitions worked. From what I can tell, they did.
As it was for many of the museum's patrons, the exhibition was very personal to me. My parents' families are Mexican and Polish. When I began the process of assembling Who Are We Now?, I felt no particular kinship with African Americans as a group. I named the exhibition Who Are We Now? precisely because what I learned from The African Presence in M\xe9xico and during the research process changed the way that I think of myself and my family.
The turning point came when I sent my father the draft of my article for the catalog to edit. He took the manuscript to San Antonio with him while visiting his family—the Mexican side of our family. He called me from Texas after reading my article to tell me that my cousin Sarah is Black. I had to stop myself from brushing off the idea and really consider the fact that the African presence touches all of Mexico, as the exhibitions at the Museum show. Many staff members at the Museum are considering similar questions of identity within their own families as well. When I saw the picture of Sarah that my father sent me, my initial reaction was to think that she looked simply Mexican, not necessarily Black. She almost certainly thinks of herself the same way that I do. But Mexican-ness includes an element of Blackness, which is something that we're not used to acknowledging.
My work on Who Are We Now? became an act of solidarity between my Mexican self and African Americans in the moment I saw the connection between us. Knowledge of history produced a feeling of solidarity in me that became translated directly into action, beginning with giving the exhibition a name that encourages people to question their own histories. The responses to the exhibition, by the press and the public, have been overwhelmingly expressions of gratitude that the Museum has chosen to tell these stories that bring people together, and that we have succeeded in doing so in a very respectful way. Our success was largely the result of intense work by the Steering Committee made up of staff of the mfacm and African American leaders such as Jacqueline Atkins, the director of Museums in the Park; Amina Dickerson, the director of corporate contributions for Kraft Foods; and Tracye Matthews, the associate director of the Center for the Study of Race, Politics, and Culture. It seems that this would go without saying, but, as the political climate in this country clearly shows, it doesn't: it is important to bring everyone with a stake in the result into any discussion from the beginning.
All of the exhibitions included images of people who look African (be that Afro-Mexican or African American) and people who look Mexican appearing noble, dignified, and empowered. As a white Latina, I didn't understand until recently why people needed to see themselves on the wall of exhibitions or in the pictures in textbooks or on TV in order to become invested in whatever discussion was taking place. I have always seen myself in these places, and so I, like most people with white skin, took that for granted. I think, though, that it has been a good experience for African Americans to come into a Mexican museum in an overwhelmingly Mexican neighborhood in Chicago and see their people on the wall. Seeing themselves, in and of itself, sends a strong message of solidarity that becomes even stronger when the visitors understand its basis in history.
We need to continue to use the history that binds Mexicans and African Americans together to unite these groups. This can be done in numerous ways, including exhibitions, public events, and (especially) by revising curricula in schools to include this information. In the moment that African Americans and Mexicans see each other as family, they will begin to share common goals and empathy. Once that happens, they will work together as a majority that is capable of generating real change.


text:
Nacogdoches County chief deputy accused of perjury accepts pre-trial diversion
By Donna McCollum | March 22, 2017 at 3:50 PM CDT - Updated August 12 at 11:31 PM
Stephen Godfrey (Source: Nacogdoches County Jail)
Godfrey said in a Facebook post at 11 Tuesday night that, 'It's finally over'. He's been answering responses ever since. (Source: KTRE Staff)
Stephen Godfrey takes aim at getting back to work following his agreement to a pre-trial diversion. (Source: KTRE Staff)
Defense attorney David Dobbs, Stephen Godfrey and his wife provide an interview following a pre-trial hearing. (Source: KTRE Staff)
NACOGDOCHES, TX (KTRE) - Stephen Godfrey, the chief deputy with the Nacogdoches County Sheriff's Office has accepted a six-month pre-trial diversion in connection to the third-degree felony aggravated perjury charges that were filed against him in 2016.
Godfrey was indicted on the charges in August of 2016. The indictment states Godfrey lied about his college degrees during a suppression hearing on Jan. 15, 2015, and again during a suppression hearing on Dec. 4, 2015. He allegedly stated both times that he had bachelor's degrees in criminal justice and psychology.
"I'm not admitting to any crime," Godfrey told the East Texas News Wednesday. "I haven't pleaded guilty to any any crime because I did not commit a crime. I gave an explanation of what I said, and I'm ready for this to be over."
According to Nacogdoches County District Attorney Nicole LoStracco, Godfrey's indictment will remain pending until the six-month pre-trial diversion ends. LoStracco said that Godfrey will report to the Nacogdoches Probation Department by mail on a monthly basis.
Godfrey will also be required to pay $300 in court fees and a $60 probation fee each month.
The NCSO chief deputy was also required to a sign a state of stipulation statement, LoStracco said.
In the the statement, Godfrey said that he testified under oath at suppression hearings in the 145th Judicial District Court on Jan 15 and Dec. 4 of 2015 that he had a psychology degree from Stephen F. Austin State University. He also said he testified that he is an instructor for the El Paso Intelligence Center and the Drug Interdiction Assistance Program.
"I now understand those statements were not accurate," Godfrey said in the statement.
Godfrey wrote that he does not have a degree in psychology.
"My degree is a bachelor of applied arts and sciences with a concentration in public safety and a professional development in private security," Godfrey said in the statement.
Godfrey also said in the statement that he now understands that requirements for a degree in psychology in 2002 called for a student to complete 21 core psychology courses, "including but not limited to (5) 400-level courses and (2) 300-level courses."
"I completed (1) 100-level course and (1) 300-level course," Godfrey said in the statement. "My college credits do not not meet the requirements for a degree in psychology."
In the statement, Godfrey seemed to address other possible allegations as well.
"I was previously an instructor for DIAP, but my certification expired, and I did not seek re-certification after DIAP and EPIC separated into two separate entities," Godfrey wrote in the statement. "Therefore I am not currently a certified instructor for DIAP. I now understand that to be currently considered an instructor for DIAP, I would have to have taken their re-certification course within the past 12 months or taught a DIAP course within the preceding 12 months of my testimony. I have not met either of those requirements since at least 2006."
At the end of the statement, Godfrey wrote that he understood the state is alleging that he provided inaccurate testimony with the intent to deceive, but he was standing by his contention that he was "simply mistaken" in his testimony.
David Dobbs, Godfrey's defense attorney, said Godfrey's statement should not be interpreted as an admission of guilt.
"If you look at the statement, the last sentence indicates that he continues to insist that he had no intent to deceive anybody, which means he did not commit an offense. Consistent with his polygraph results."
LoStracco said her office, Godfrey, and his defense attorney have been talking about all of the options for the past eight months. She said Godfrey and his defense attorney approached her Tuesday and requested the pre-trial diversion. However, Godfrey and Dobbs dispute that claim. Dobbs said he offered up the pretrial diversion months ago, but prosecutors weren't receptive to the proposal.
The pre-trial diversion was the result of a seven-hour meeting.
LoStracco said her office found additional possible charges against Godfrey, and they were prepared to present it to the grand jury. She said they pursued the perjury case because it was easier.
Once the pre-trial diversion is completed, the charges won't go off Godfrey's record until he files a motion of expunction. LoStracco said she won't contest the motion of expunction once it is filed.
LoStracco said that Godfrey has been "Brady listed," which basically means he will never be able to testify in a felony case in Nacogdoches County as long as LoStracco is the district attorney. It also means that other counties could prevent him from testifying in criminal cases as well.
In an interview Wednesday morning, Dobbs said that his client's employment status may still be in question because Nacogdoches County Sheriff Jason Bridges plans to conduct an internal investigation of the allegations Godfrey.
KTRE Reporter
Donna McCollum produces stories for the weekday newscasts at 5, 6, and 10. Nacogdoches County keeps her busy, but she also covers news stories in adjacent counties.


text:
iPhone 11 Launches With Dual 4K Cameras, Lower Price and A13 Chip
Apple's new phone is here.
The iPhone 11 has arrived. Apple's next-generation smartphone launched Tuesday to great fanfare, offering a much-improved camera, an even faster processor, and even lower price.
The phone, the successor to the 2018 iPhone XR, improves on its predecessor in a number of ways. It adds a second, wide-angle camera lens alongside the original single lens. It offers the A13 Bionic chip, billed by the company as the fastest CPU and GPU in a smartphone. It also comes in at $699, $50 cheaper than the $749 iPhone XR.
"It is jam-packed with great new capabilities and an incredible new design.
"iPhone 11 [is] the next generation of iPhone, and it is jam-packed with great new capabilities and an incredible new design," Apple CEO Tim Cook told the audience at the Steve Jobs Theater in Cupertino, California on Tuesday. The building forms part of the new Apple Park campus, one of the last projects Steve Jobs worked on at the company.
The front of the iPhone 11. Apple
iPhone 11: Features Coming to the New iPhone
The iPhone comes in six colors: purple, white, yellow, green, black, and (Red). It has a 6.1-inch LCD screen, paired with a spatial audio system that delivers what the company calls an "immersive theater-like experience." The anodized aluminum is paired with new, tougher glass that the company claims is the toughest ever on a smartphone.
The camera lenses, milled from a single piece of glass, enable seamless switching between regular and wide-angle shots in both photos and videos. The regular camera is a 26 millimeter f/1.8 camera with a six-element lens, optical image stabilization and 100 percent focus pixels. The other is an ultra-wide camera with a 13 millimeter f/2.4 camera with a five-element lens and a 120-degree field of view. Both cameras offer 12 megapixels.
The in-phone processing enables multi-scale tone mapping to make colors pop with greater detail. A new portrait lighting mode enables high-key mono lighting. Night Mode, another new addition, automatically enables brighter pictures that could help the iPhone take on the Google Pixel.
Regular versus night mode. Apple
On the video side, the device can capture 4K resolution video at 60 frames per second, offering extended dynamic range on both cameras. On the front camera, slow motion video is now possible. Apple has dubbed the videos produced by the latter feature "slofies."
The ultra-wide camera. Inverse
Beyond the camera features, the iPhone 11 is also water-resistant up to two meters for 30 minutes. It supports faster gigabit-class LTE connections and Wi-Fi 6, but no 5G. It offers one hour more battery life than its predecessor, the iPhone XR that was previously billed as the iPhone with the longest battery life. The new device is $50 cheaper than its predecessor, at $699.
iPhone 11: Why the Lack of Changes?
So why the few changes? Apple's new device makes some welcome additions, but on the whole bears strong similarities to the iPhone XR. It has the same 6.1-inch LCD screen, suggesting it could feel very similar to the older device.
From the iPhone 3G in 2008 to the iPhone 5S 2013, Apple phones followed a "tick-tock" pattern, where a big redesign in one year's lineup would be followed by a smaller, internals-focused release the next year. Think how the 3G was replaced by the 3GS, the 4 by the 4S, and the 5 by the 5S.
From the iPhone 6 onwards, Apple seems to have switched to a slower "tick-tick-tock" pattern. The iPhone 6, 6S and 7 all kept the same basic design for three years. The iPhone X in 2017 was the first phone in three years to shift the design, switching to a button-free front and face recognition, a setup largely retained for the iPhone XS.
Why the slowdown? One possibility is that people upgrade phones less. A Kantar study in 2017 found the average American consumer held onto their phone for 20.5 months in 2013 before upgrading. But by 2016, this had extended to 22.7 months, just shy of two years. The trend was also observed in China and five European Union countries.
Apple's full line of in-production iPhones and their prices, as revealed on Tuesday, September 10, 2019. Apple
The iPhone has also taken a less prominent role in the company's earnings. In the firm's most recent quarterly report, iPhone revenue fell below 50 percent of the company's total for the first time since 2012. After a high of 231 million units sold in 2015, annual iPhone sales have been bobbing around the 215 million mark ever since.
The iPhone 11: it's part of a big new strategy, but will it work?


Based on sequence variation in the UL55 gene that encodes glycoprotein B (gB), human cytomegalovirus (CMV) can be classified into four gB genotypes. Previous studies have suggested an association between CMV gB genotype and clinical outcome in patients who underwent an allogeneic hematopoietic stem cell transplant (HSCT). The goals of this study were identify patients with active infection caused by CMV in recipients of HSCT; determine the prevalence of CMV genotypes in the study group; correlate genotype with CMV disease, acute GVHD and overall survival.
The diagnosis of active CMV infection after allogeneic HSCT was detected by antigenemia (AGM) and/or nested-PCR (N-PCR). Positive samples from patients with active CMV infection were submitted to genotyping using N-PCR to amplify a region of UL55, followed by restriction analysis based on HinfI and RsaI digestion. Real-time PCR (qPCR) was used to determine the viral load during active CMV infection and antiviral treatment.
Sixty-three allogeneic HSCT recipients were prospectively evaluated; 49/63 (78%) patients were infected with CMV genotypes – gB1 19/49 (39%), gB2 17/49 (35%), gB3 3/49 (6%), gB4 7/49 (14%) – and 3 (6%) had mixed CMV genotypes (gB1 + gB3, gB1 + gB4 and gB2 + gB4). Characterized by gastrointestinal disease, CMV disease occurred in 3/49 (6.1%) patients, who had CMV gB3 genotype. These gB3 genotype patients presented an increasing AGM number, mean 125 (± 250) (P = 0.70), and qPCR copies/ml, mean 37938 (SD ± 50542) (P = 0.03), during antiviral treatment, when compared with other CMV genotypes. According to CMV genotypes, stratified overall survival was 55% for gB1, 43% for gB2; 0% for gB3 and 57% for gB4 (P = 0.03).
One of the restrictions of the presented study was the low number of CMV gB sub-cohorts). However, we demonstrated that the frequency of active CMV infection in this HSCT population was high, and the most prevalent genotype in these patients with active CMV infection was gB1 and gB2 genotype (74%). In Brazil, HSCT recipients seem to carry mainly gB1 and gB2 CMV genotype.
Cytomegalovirus (CMV) remains the most important cause of serious viral infections in allogeneic hematopoietic stem cell transplant (HSCT) recipients . CMV glycoprotein B (gB) is the major CMV envelope glycoprotein and it is encoded by UL55 gene. CMV gB has been implicated in host cell entry, cell-to-cell viral transmission and fusion of infected cells [2–4]. Chou and Dennison (1991) devised a method of CMV genotyping based on UL55 gene nucleotide sequence that encodes a variable region encompassing the protease cleavage site. They found that there were HinfI and RsaI restriction sites between nucleotides 1344 and 1440. Amplification of this region, using polymerase chain reaction (PCR) followed by restriction analysis, demonstrated the existence of four different gB genotypes . Since gB has been implicated in host cell penetration, it is possible that four types differ with respect to tissue tropism and virulence. Many studies have attempted to find a correlation between gB genotype and the occurrence of CMV-associated disease in immunocompromised patients; however, it remains unclear whether certain gB genotypes are associated with an increased frequency of disease . There are few references about functional differences that may exist among various CMV strains. It was reported that the existence of CMV variants played an important role in the pathogenesis of diseases, as these variants affected several genes that might be responsible for different diseases related to active CMV infection [7–10]. Recently, comparative sequence studies have been used to define the extent of interstrain variation in selected coding regions of the CMV genome. Clinical CMV isolates were found to adopt one of four gB sequence configurations at certain variable loci, and a genotyping scheme was proposed [11–13]. Although gB genotypes display significant amino acid variations in their variable domains, including changes that affect glycosylation sites, the functional consequences of these variations have not yet been explored [14–24].
This study aimed to prospectively analyze gB gene of CMV in allogeneic hematopoietic stem cell transplant (HSCT) recipients with human active CMV infection to determine the distribution of gB genotypes and their possible impact on overall survival, acute GVHD and CMV disease.
This study comprised 63 adult patients with malignant and nonmalignant hematological diseases, who underwent a myeloablative or nonmyeloablative allogeneic HSCT at the Hematopoietic Stem Cell Transplantation Unit of the University of Campinas Teaching Hospital, with related or not related HLA identical donors and graft source from bone marrow or peripheral blood. The blood products used were neither screened for CMV antibody nor filtered to depleted leukocytes, although all had been irradiated. The conditioning regimens and GVHD prophylaxis were selected according to ongoing protocols at the University Hospital. These patients were prospectively monitored for active CMV infection from March 2007 to May 2010, using antigenemia (AGM) assay, nested-polymerase chain reaction (N-PCR) in leukocytes, and real-time polymerase chain reaction (qPCR). Patients with active CMV infection results were treated with preemptive ganciclovir. CMV genotypes of all positive patients were obtained by N-PCR and confirmed by sequencing, using primers from the glycoprotein B (gB) region of CMV (UL55) and restriction enzyme analysis (RFLP) with HinfI and RsaI enzymes. Real-time polymerase chain reaction (qPCR) assay was used to quantify the CMV load during active CMV infection and antiviral preemptive treatment. The protocol was designed in accordance with the requirements for research involving human subjects in Brazil and approved by the Institutional Review Board. Informed consent was obtained from all patients. Clinical characteristics of the study subjects are summarized in Table 1.
GVDH graft-versus-host disease, CMV cytomegalovirus.
The study was approved by the National Research Ethics (CONEP) of Brazil (680/2006).
Active CMV infection was defined based on at least one of the following criteria:  one or more positive cells in the AGM assay, and  two or more consecutive positive N-PCR results. For the diagnosis of CMV disease, the active infection had to be accompanied by clinical symptoms and histopathological identification of CMV . Recurrence of CMV infection was defined as active CMV infection occurring after negative N-PCR and/or AGM assays, following treatment of the initial episode of infection. Late active CMV infections and diseases were defined as those occurring more than 100 days after transplant.
AGM assay was done at least once a week after engraftment, according to Bonon et al., 2005, with some modifications. EDTA-treated blood samples were fractionated by erythrocyte lyses. Granulocytes were then centrifuged to prepare cytospin slides (2 × 105 granulocytes per slide). After air-drying and fixing the slides in formaldehyde, they were immunostained using the well-defined C10/C11 antibody cocktail to detect the CMV lower matrix phosphoprotein (pp65), an early antigen in virus replication, which is abundantly present in antigen-positive polymorphonuclear cells. The CMV Brite™ Turbo Kit (Iq Products) is a rapid new version of the first FDA registered immunofluorescence antigenemia kit for in vitro CMV diagnosis. Slides were made in duplicate .
CMV DNA in blood specimens was detected by nested PCR using the primers described by Demmler et al. and Shibata et al. (1988). Briefly, leukocytes remaining from the CMV antigenemia assay were lysed and the DNA was precipitated. The primers were selected from the MIE region of CMV-AD169. The size of the PCR amplification products was 159 base pairs. The same protocol was used to amplify the human b-globin gene sequence to guarantee the quality of the extracted DNA [27, 28].
PCR primer and probe sequences were selected from the US17 region of CMV AD169. The real-time protocol was according to Peres et al., 2010. The forward and reverse CMV primers were 5′ GAAGGTGCAGGTGCCCTG 3′ and 5′ GTGTCGACGAACGACGTACG 3′, respectively. The Taq Man probe selected between both primers was fluorescence labeled with 6-carboxyfluorescein at the 5′ end as the reporter dye and 6- carboxytetramethylrhodamine at the 3′ end as the quencher (5′FAM ACGGTGCTGTAGACCCGCATACAAA TAMRA3′).
A search of databases indicated that neither the primers nor the probes shared significant homology with any known nucleotide sequence except of CMV. The real-time PCR was performed with a mixture containing: 3 mM MgCl2; 10 μM dATP, dCTP, dGTP, dTTP; 5 U/μl of Platinum Taq (Invitrogen), 60 ng DNA templates, 150 nM of forward and reverse primers (CMVUS17F-CMVUS17R for CMV detection) and 2 μM of the specific Taq Man CMV probe (PE Applied Biosystems). The single PCR was performed in 96-well microliter plates under the following conditions: 1 cycle at 50°C for 2 minutes, 95°C for 10 minutes and 45 cycles at 95°C for 15 seconds and 60°C for 1 minute. The ß-actin gene amplification was performed under the same PCR conditions described above for the reaction control, using 2 μM ß-actin probe (FAM™ Probe), 3 μM ß-actin forward primer, and 3 μM ß-actin reverse primer (TaqMan® ß-actin detection reagents - Applied Biosystems) .
Oligonucleotide primers used for PCR amplification were chosen in a region of high sequence variability in the CMV gB gene, as previously published by Chou and Dennison (1991), and were synthesized commercially (Invitrogen, by Life Technologies, Brazil). The first and the second rounds of amplification were carried out in a total volume of 50 μl, using 200 ng DNA extract (1st) and 1 μl PCR product (2nd) and 49 μl PCR mix (10 mM Tris pH 8.3, 50 mM KCl, 2 mM MgCl2, 200 mM of each dNTPs, 1.25 U of recombinant Taq DNA polymerase and 0.4 mM of each primer (Invitrogen, by Life Technologies, Brazil). After amplification, 5 μl of the amplified product were electrophoresed on 2% agarose gel (Gibco-BRL, Grand Island, NY) containing ethidium bromide, and the gel was photographed under UV illumination. The AD169 strain was used as a positive control; an uninfected DNA sample or water was used as a negative control .
Approximately 10 μl of nested PCR product were digested at 37°C overnight, using 1 U of the restriction enzymes, Rsa I and Hinf I (Gibco-BRL). Sequences were analyzed on a 2% agarose 1000 gel (Gibco-BRL). The four types of gB were distinguished by their different patterns of fragment lengths, as described .
To determine the sequences of the CMV gB genotype samples, the PCR products were purified using the PCR purification kit (Quiagen) and subcloned into the pGEM-T vector (Promega, Madison, WI, USA). Sequences were obtained using the ABI 310 genetic analyser (Applied Biosystems, Bedford, MA, USA) with proper primers, and they were aligned with known CMV variants in GenBank afterward. The sequences of gB1, gB2, gB3 and gB4 were very similar to GenBank M60927, M60931, M60930 and M60926 respectively.
The descriptive analysis summarized patient sociodemographic characteristics, as well as transplant, GVHD and CMV serologic status of donors and receptors. The Fisher's and Kruskal-Wallis tests were applied for categorical and continuous variables, respectively. The Kaplan-Meier method was used to estimate overall survival. Stratified overall survival, according to CMV genotypes, was compared with the log-rank test. Death by any cause was considered as event. The gB1 + gB3 mixture was clustered into genotype gB3 for statistical purpose, since these strains had the same behavior in the study.
The other two mixtures detected, gB1 + gB4 and gB2 + gB4, were not grouped, as they did not identify any pattern of behavior. The p-value < 0.05 was considered significant. The statistical analyses were performed using the software SPSS 14 (Statistical Package for Social Sciences).
Among the 63 patients, 49 (78%) had active CMV infection detected by AGM and/or N-PCR tests. Active CMV infection occurred within a median time of 38 days (1–150) after the transplant. The median time to detect active CMV infection by AGM and N-PCR was 46 (14–150) and 34 days (1–140), respectively. The incidence of active CMV infections is summarized in Table 2.
N-PCR nested polymerase chain reaction, AGM antigenemia.
Forty-nine patients with active CMV infection were submitted to CMV genotyping using RFLP. Nineteen out of 49 (39%) recipients had gB1 genotype; 17 out of 49 (35%), gB2; 3 out of 49 (6%), gB3; and 7 out of 49 (14%), gB4. There were three patients (6%) who had a combination of two different CMV genotypes (gB1 + gB3, gB1+ gB4 and gB2 + gB4).
Eight samples (two with gB1, two with gB2, two with gB3 and two with gB4) and three mixed CMV genotype samples were sequenced. The patients' CMV sequences were 98-99% identical to CMV sequences in GenBank when compared.
Among the 49 patients who had active CMV infection, three (6%) developed CMV disease manifested as gastrointestinal disease, two had gB3 and one had a mixture of gB1 + gB3 strains.
The active CMV infection recurrence detected by HCMV antigenemia and/or nested PCR occurred in 9 out of 49 (18%) patients within a median of 92 days (61–138), with the same infecting strain caused by the first active CMV infection. The recurrence occurred in 1 out of 9 (11%) cases with gB1, in 1 out of 9 (11%) with gB2, in 3 out of 9 (33%) with gB3, and in 4 out of 9 (44%) with gB4.
Seventeen out of 49 (35%) patients with CMV active infection developed grade II-IV acute GVHD. Among the patients with acute GVHD, 12 out of 17 (70.6%) had acute GVHD before diagnosis of active CMV infection; however, 5 out of 17 (29.4%) patients had active CMV infection before acute GVHD. Diagnosis of active CMV infection occurred within a median of 20 days [6–35] after diagnosis of acute GVHD, and acute GVHD occurred within a median of 45 days (27–59) after active CMV infection. The frequency of II-IV acute GVHD, according to CMV gB genotype, showed that 8 out of 19 gB1 patients (42%), 1 out of 17 gB2 patients (6%), 3 out of 7 gB4 patients (43%) had aGVHD, and all 4 gB3 patients, including the mixture gB1 + gB3, had aGVHD (P = 0.008).
At the active CMV infection onset, gB3 genotype presented the highest number of AGM-positive, mean 251 (SD ± 499), and gB2 the highest qPCR copies/ml, mean 1733 (SD ± 6272). However, the difference between the four genotypes for either AGM or qPCR was not significant (AGM – p-value = 0.73; qPCR - p-value = 0.13). These results are summarized in Table 3.
AGM antigenemia, qPCR real-time polymerase chain reaction.
*Mean qPCR in logarithm base 10; n = number of pp65 CMV positive cells/2 × 105; SD = standard deviation; AGM – p-value = 0.73; qPCR - p-value = 0.13 (kruskal-WallisTest).
In spite of preemptive treatment for active CMV infection, three out of four gB3 patients developed gastrointestinal disease. In two out of those three patients, CMV replication occurred after onset of grade II-IV acute GVHD. Interesting, during preemptive treatment, these gB3 genotype patients presented an increasing AGM number, mean 125 (± 250) (p = 0.70), and qPCR copies/ml, mean 37938 (SD ± 50542), when compared with other CMV genotypes (p = 0.03). These results are presented in Table 4 and Figure 1.
*Mean qPCR transformed in logarithmic base 10; n = number of pp65 CMV positive cells/2 × 105; SD = standard deviation. Antigenemia – P-value = 0.70; qPCR - P-value = 0.03 (kruskal-WallisTest).
Antigenemia and viral load by qPCR in the monitoring of preemptive antiviral treatment stratified by genotypes.
Among the 49 patients with active CMV infection, 25 (51%) died. The distribution of causes of death were as follows: relapse, 10 out of 25 (40%); bacterial or fungal infection, 10 out of 25 (40%); GVHD, 2 out of 25 (8%); cardiac toxicity, 1 out of 25 (4%); pulmonary hemorrhage, 1 out of 25 (4%); CMV disease, 1 out of 25 (4%).
After a median follow-up of 17 months [1-52], the overall survival for patients with active CMV infection was 45% (95% CI 39-61%); whereas the stratified overall survival, according to CMV genotypes, was 55% for gB1, 43% for gB2; 0% for gB3 and 57% for gB4 (p = 0.03), as shown in Figures 2 and 3.
In this cohort of Brazilians patients with active CMV infection, the most frequent genotypes were gB1 and gB2 (74%). Moreover, all patients who had CMV gastrointestinal disease, higher viral load during preemptive antiviral treatment, acute GVHD grade II-IV and worse survival were gB3 genotype.
The high incidence of active CMV infection detected either by N-PCR or AGM in our population was comparable to prior reports and they were equally effective for diagnosis of active infection and disease [26, 30–32]. Although the proportion of CMV seronegative donors or recipients has been small, almost all positive N-PCR and AGM results were from CMV seropositive patients.
According to previously described CMV envelope glycoprotein genotypes, we were able to confirm that CMV gB genotyping could reliably identify one of four established gB genotypes, using two restriction endonucleases – HinfI and RSAI – to digest the PCR-amplified variable region of UL55, encoding the protease cleavage site [5, 33]. GB1 and gB2 were the most frequent genotypes in this study, and they occurred in similar proportions (39% and 35%, respectively). These results are in line with other studies, including one from our group performed in a Brazilian pediatric renal and hematopoietic stem cell transplantation cohort [7, 34–37], but not with a report from Chinese HSCT patients, where gB1 and gB3 were the prevalent genotypes [38, 39]. Furthermore, in our population, the proportion of mixed genotypes was rare (6%), that is comparable to recent reports which showed ranges from 5% to 25% [6, 38, 40].
CMV gB genotype may be an important determinant of viral virulence because gB has been implicated in several essential steps in CMV pathogenesis, such as virus entry, cell fusion, and cell-to-cell spread. The virulence of different CMV strains may be an important factor in the occurrence of CMV disease because of genetic variation in genes that are involved in host cell penetration, tissue tropism, or replication, and polymorphism in the viral genome may play an important role [40–42].
Outcomes of different CMV genotypes with clinical manifestations are conflicting. CMV gB3 and gB4 were reported to be associated with myelosuppression in HSCT patients , gB3 with high incidence of pneumonitis , and gB1 with invasive disease in solid organ transplantation [36, 38]. A recent Brazilian study involving AIDS patients demonstrated that gB2 genotype was associated with worse prognosis . In prior studies, mixed CMV genotypes were observed to be associated with a high prevalence of CMV disease in solid-organ transplant patients [6, 44, 45], but in our study we did not find these results.
Neither cases of myelossupression and pneumonitis, nor a high prevalence of CMV disease in mixed CMV genotypes were seen in our data, but intriguing all cases of CMV disease were associated with the gastrointestinal tract, and all of them had genotype gB3. Hence, gB3 genotype might confer a specific virulence advantage for that genotype in our cohort. Although some associations have been described so far between a certain virus subtype and the development of individual disease these analyses were greatly complicated by the huge genomic background of CMV, by the large variety of individual host-virus relations and by differences in the geographic or demographic subtype distribution .
Acute GVHD and CMV replication are pathogenetically associated. In this report, most patients had GVHD before the onset of CMV infection, confirming what several studies have already shown that acute GVHD and its treatment put patients at risk for CMV replication [43, 47–49]. In contrast, the role of CMV replication as a cause of acute GVHD is controversial. One recent small study found no effect of CMV replication on subsequent development of acute GVHD . Others demonstrated the reciprocal finding that patients are at significant risk of developing acute GVHD during CMV replication [43, 51].
Torok-Storb et al.  reported that CMV gB3 was associated with a reduced risk of GVHD in HSCT patients. Wu et al.  failed to demonstrate an association of B genotypes with GVHD. We found a different distribution of II-IV acute GVHD according to gB genotypes, and all gB3 genotypes were involved with acute GVHD, highlighting a possible association of that genotype with acute GVHD.
We observed that the mean load viral was higher in gB2 at the diagnosis; however, during the preemptive antiviral treatment, the viral load detected, either by qPCR and AGM, showed an increase in gB3 genotype. Clearly, genotype gB3 showed a different behavior when compared with other genotypes, leading to believe that this might be associated with a more severe and uncontrolled infection that caused all cases of gB3 gastrointestinal CMV disease and a worse survival in our population.
Perhaps, not gB3 genotype per se but its low frequency in the patient's cohort may be associated with bad outcome of the CMV infection. If this genotype is rare in this region, higher is the probability of primo infection in this population during the transplantation, that is associated with insufficient or delayed immune response, prolonged high level of virus replication and higher risk of CMV disease and related complications.
One of the restrictions of the presented study was the low number of CMV gB sub- cohorts). However, we demonstrated that the frequency of active CMV infection in this HSCT population was high and the most prevalent genotype in these patients with active CMV infection was gB1 and gB2 genotype (74%). In Brazil, HSCT recipients seem to carry mainly gB1 and gB2 CMV genotype.
We are also very grateful to our patients for their participation in this trial and the medical staff for their collaborative efforts in the excellent care provided to patients and families.
This work was supported by Fundação de Amparo à Pesquisa do Estado de São Paulo (grant 07/52388-1).
ACV study design, collected data, analyzed data and wrote the paper; DCD study design, collected data, analyzed the data and wrote the paper; ECMM performed the statistical analysis; SHB, RMBP, CRCC, DMA updated the collected the data for the study; FJPA, GO-D, VCAF, CADS reviewed the manuscript; SCBC study design and reviewed the manuscript. All authors read and approved the final manuscript.