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Effect of carvedilol versus nebivolol on insulin resistance among non-diabetic, non-ischemic cardiomyopathy with heart failure
Yasser Gaber Metwally1,
Heba Kamal Sedrak2 &
Inass Fahiem Shaltout2
Although B-blockers provide unequivocal benefits in heart failure (HF) management, some B-blockers worsen insulin resistance. It will be a promising strategy to recruit such a B blocker that did not worsen or can even improve insulin resistance (IR).
So, this study aimed to assess the effect of two of the third-generation B-blockers (carvedilol versus nebivolol) on insulin sensitivity state in non-diabetic patients with non-ischemic cardiomyopathy with heart failure.
Out of 43 patients enrolled, 58.1% represented the carvedilol group while 41.9% represented the nebivolol group. Nebivolol improves insulin resistance-related variables (fasting glucose, fasting insulin, and HOMA-IR; P < 0.001, 0.01, and 0.01 respectively). The percentage of change at homeostasis model of assessment (HOMA-IR), indicative of insulin sensitivity status, between baseline versus at 3-months follow-up level of intra-group comparison was increased by 4.58% in the carvedilol arm whereas it was decreased by 11.67% in the nebivolol arm, and the difference on the intragroup level of comparison was significant (P < 0.001 and 0.01 respectively).
Nebivolol improves insulin resistance-related variables .Nebivolol may be recommended as the B blocker of the first choice for those with non-ischemic cardiomyopathy heart failure with evident insulin resistance; however, larger scaled prospective multicenter randomized trials are needed for confirming our favorable results.
Myocardial systolic dysfunction is associated with sympathetic hyperactivity evidenced by increased plasma norepinephrine (NE) level, central sympathetic outflow, and NE plasma spillover [1]. Measurement of cardiac NE plasma release using isotope dilution method indicates that in untreated heart failure patients, cardiac NE spillover is increased as much as 50 times similar to levels seen in healthy hearts during maximal exercise [2]. However, in contrast to increased muscle sympathetic nerve activity and NE spillover, patients with heart failure with reduced ejection fraction (HFrEF) may have decreased NE concentration inside the cardiac cells, together with a reduction of post-synaptic beta-receptor density [3]. However, it should be realized that plasma NE level does not necessarily reflect the sympathetic activity level in skeletal muscle [4]. The neurohormonal hyperactivity associating HfrEF represents a compensatory mechanism to maintain cardiac output. The neuronal limb of such response is represented by the sympathetic nervous system (SNS), whereas the humoral limb is represented by the renin-angiotensin aldosterone axis [5]. The overactivation of the sympathetic nervous system in congestive heart failure (CHF) patients is thought to contribute to hyperinsulinism and insulin resistance (IR) [6]. A moderate increase in plasma NE has been observed to reduce glucose tolerance, and insulin sensitivity may be accomplished by increased lipolysis and free fatty acid levels [7].
Moreover, a small increase in plasma NE has been reported to increase fasting blood glucose through transient stimulation of basal hepatic glucose output without altering basal glucose utilization, insulin, or glucagon secretion [8]. On the other hand, insulin does also stimulate the SNS. According to animal and human studies, it has been demonstrated that short-term insulin infusion stimulates the SNS activity [9]. It is evident that acute physiological as well as pharmacological euglycemic hyperinsulinemia increase plasma catecholamine concentration [10]. Furthermore, it is documented that hypertensive patients show an enhanced SNS activity in response to insulin [11]. Hyperinsulinemia may therefore also influence adrenergic activity, contributing to further insulin-resistance worsening (vicious circle).
Evident data suggest that heart failure may not only precipitate insulin resistance but also lead to IR worsening [12]. Although B-blockers provide unequivocal benefits in heart failure management including improving survival, some B-blockers worsen insulin resistance [13, 14]. However, it will be a promising strategy in heart failure therapy to recruit such a B blocker that did not worsen or can even improve insulin resistance. We hypothesized that nebivolol could have a better effect on insulin resistance than carvedilol among non-diabetic, non-ischemic cardiomyopathy with heart failure. Accordingly, this study aimed to investigate the effect of carvedilol versus nebivolol on insulin resistance among non-diabetic, non-ischemic cardiomyopathy with heart failure.
This study was conducted from March 2018 to May 2020.
Forty-three consecutive patients with non-diabetic, non-ischemic cardiomyopathy with CHF were enrolled in this study. Patients were eligible if mild to moderate CHF present ejection fraction (EF%) is between 30 and 40%, New York Heart Association Classification (NYHA class) is ranged between I and II, and age is between 40 and 80 years. Diabetes mellitus, known ischemic heart disease or previous CABG, active myocarditis, significant valve lesion, alcoholics, severe CHF (EF < 25%), NYHA class III and IV, patients in need for CCU admission, or patients that had been admitted to CCU within the last 3 months, patients who are fibrillating or with sustained ventricular tachycardia, patients with chronic kidney disease or with active liver disease alanine aminotransferase (ALT) > 3 folds, and patients with contraindication to B-blockers were exclusion criteria.
They were randomly assigned by a computer program. Patients were assigned to one of the two arms of the study either to receive carvedilol (carvedilol group n = 25( or nebivolol group; n = 18).
After 2-weeks wash-out period (e.g., the patients received no B blocker treatment for a period of 2 weeks prior to their inclusion, to eliminate previous B blocker effect before starting carvedilol/nebivolol), our study protocol started including the following both at the beginning of the study as well as at the study end: NYHA class assessment, vitals (pulse/minute, blood pressure), body mass index (BMI), EF% (by Simpson Method), 6-minute walk test [15], routine laboratory investigations, fasting glucose level, glycosylated hemoglobin (HbA1C%), and fasting insulin of the blood samples collected for measurement of glucose and insulin. Plasma glucose was measured by glucose oxidase method with a Beckman glucose analyzer, and plasma insulin concentrations were determined by radioimmunoassay.
Measurement of insulin sensitivity
The estimate of insulin resistance by homeostasis model of assessment (HOMA-IR) derives an estimate of insulin sensitivity from the mathematical modeling of fasting glucose and insulin concentrations [16]. In comparison to the euglycemic clamp, the HOMA-IR model is an easy, practical, and inexpensive method for assessing IR. We applied the HOMA-IR in non-diabetic participants using the following formula [17]: fasting insulin level (μU/ml) × fasting glucose (mg/dl)/405, subjects whose values exceeded the 75th percentile (i.e., 2.0) were considered to have insulin resistance (HOMA-IR index) [18].
Measurement of norepinephrine
After 30 min rest, 9 ml of blood was drawn from an ante-cubital vein through the intravenous cannula, into pre-chilled tubes containing 15 ml EGTA (ethylene-glycol-tetra acetic-acid) and 12 mg glutathione. The tubes were kept on ice before and after blood sampling and were immediately centrifuged at 4 °C and 3000 rpm for 15 min, and then stored at − 80 °C until analysis by high-performance liquid chromatography [19]. All blood samples from the same patient were analyzed within the same setup.
Measurement of plasminogen activator inhibitor (PAI-1)
Blood samples were collected on ice and centrifuged immediately at 0 °C for 20 min. All plasma or serum were separated and stored at − 80 °C until the time of assay. Blood for measurement of PAI-1 was collected in vacutainer tubes containing acidified 0.105 M sodium citrate (Becton Dickinson, Rutherford, NJ), as the use of anticoagulant minimizes the contribution of platelet activation to PAI-1 antigen concentrations. PAI-1 antigen level was determined using 2-site-enzyme-linked immunosorbent assays (Imulyse, Biopol AB).
The drug dose regimen for the carvedilol arm, a starting dose of 3.125 mg bid, was given; then, the dose was up-titrated to a target dose of 25 mg bid or the maximally tolerated dose for 12 weeks. For the nebivolol arm, a starting dose of 2.5 mg/day was given; then, the dose was up-titrated to a target dose of 10 mg/day or the maximally tolerated dose for 12 weeks. The further lines of treatment for heart failure were given according to the standard guidelines [20]. After 12 weeks clinical, laboratory follow-up, data were obtained through the outpatient department (OPD) visits.
The primary endpoint was evaluating the relative effects of those two B-blockers on insulin resistance as assessed by insulin resistance index) HOMA-IR) at the baseline and after 3 months treatment.
The continuous variables were expressed in mean ± SD while discrete variables were expressed in percentage. The differences in continuous variables were checked for statistical significance by t test as appropriate; the differences in the discrete variables were checked for statistical significance by X2 test. The percentage of change at HOMA-IR between baselines versus at 3 months follow-up level of intragroup comparison was done. P value < 0.05 was considered significant. The statistical analysis was performed using SPSS.11 for Windows (SPSS Inc., Chicago, IL, USA).
Out of 43 patients enrolled, 58.1% represented the carvedilol group while 41.9% represented the nebivolol group. The demographic and clinical characteristics of our study population are shown in Table 1.
Table 1 Demographic, baseline clinical, and medications among the two groups
No significant differences were found regarding age, weight, BMI, waist circumference, gender, triglyceride, high-density lipoprotein (HDL), uric acid, hemoglobin (HB) percentage, percentage of the use of loop diuretics, RAS blockers, digoxin, or aspirin. However, the study group showed significantly higher percentage of the use of aldosterone blockers among the carvedilol group (P = 0.036).
The intragroup versus intergroup comparison of variables at the baseline versus at 3-months follow-up is shown in Tables 2 and 3.
Table 2 Intra- versus intergroup comparison of variables at the baseline versus at 3 months follow-up among the two groups
Table 3 Intra- versus intergroup comparison of 6 min walk test at the baseline versus at 3 months follow-up for the two groups
No significant differences were found neither on intragroup nor on intergroup comparison level (both at the baseline and at follow-up) regarding B blocker compliance or plasminogen activator inhibitor level. Likewise, no significant differences were found on intergroup comparison level (both at the baseline and at follow-up) regarding heart rate, blood pressure, NYHA class, EF%, or 6 min walk test.
The fasting glucose, fasting insulin, and HOMA-IR showed no significant difference on intragroup comparison (for carvedilol group only) and on intergroup comparison at baseline (for the two groups); however, these 3 variables were significantly lower among the nebivolol group (at 3 months follow-up only) both on intragroup and intergroup comparison (P < 0.001, 0.01, and 0.01) respectively (HOMA-IR changes are shown in Fig. 1).
Homeostatic model of assessment for insulin resistance in both groups. X-axis refers to the studied groups, Y-axis refers to the HOMA-IR value; G1, group 1; G2, group 2
The norepinephrine level was significantly lower in the carvedilol group (G1) on intragroup level of comparison on 3 months follow-up (P = 0.002). On the other hand, its level showed no significant difference at the nebivolol group (G2) neither on intragroup nor on intergroup comparison level with the nebivolol group (G2).
The PA-I level showed non-significant difference in both carvedilol group (G1) and nebivolol group (G2) whether on intragroup or intergroup level of comparison.
The following variables were significantly improved (at 3 months follow-up) on intragroup level of comparison, e.g., NYHA class, EF%, mean distance walked, and number of patients walked < 300 m (P = 0.03, P = 0.046, P < 0.001, P < 0.001, P < 0.001, P < 0.001, P = 0.031, and P = 0.063) respectively. Likewise, blood pressure and heart rate were also significantly decreased on intragroup level of comparison (P < 0.001, P < 0.001, P < 0.001, < 0.02, P < 0.001, < 0.001) respectively. The percentage of change at HOMA-IR, indicative of insulin sensitivity status, between baseline versus at 3 months follow-up level of intragroup comparison is shown in Table 4. The percentage of change was increased by 4.58% at the carvedilol arm whereas was decreased by 11.67% at the nebivolol arm, and the difference on the intra-group level of comparison was significant (P < 0.001 and 0.01) respectively.
Table 4 Comparison between both groups
The interrelationship between HF and IR, plasma norepinephrine, and B-blockers was discussed above [2,3,4,5,6,7,8,9,10,11, 14].
Results of our study demonstrated that nebivolol but not carvedilol improves insulin sensitivity while carvedilol but not nebivolol decreases plasma norepinephrine level. Our results of favorable effect on nebivolol on insulin sensitivity in HF patients can be explained by Manrique and colleagues [21]; they conducted an experimental study on insulin resistance Sprague-Dawley rat model treated with nebivolol for 3 weeks; they assessed HOMA-IR index as well as nicotinamide adenine dinucleotide phosphate (NADPH) oxidase activity (NADPH is an insulin metabolic signaling in skeletal muscle) before and after nebivolol treatment. They concluded that treatment with nebivolol was associated with improvement in insulin resistance with decreased NADPH oxidase activity level. A previous study [22] demonstrated that the improvement in insulin sensitivity is closely associated with decreased NADPH oxidase activity in skeletal muscle.
Previous clinical trials had investigated the value of B-blockers in CHF [23,24,25].
One study [23] conducted a prospective double-blinded, placebo-controlled randomized study on 46 CHF patients who received carvedilol or placebo to investigate whether treatment with carvedilol alter insulin sensitivity or not. They found that neither insulin sensitivity nor plasma norepinephrine had been significantly altered. Differently from this study, the present study demonstrated a significant decrease in the plasma norepinephrine level among the carvedilol group.
Ferrua et al. [24] reported that carvedilol significantly reduced HOMA-index in non-diabetic CHF patients; this was contradictory to our results.
Another pilot study investigated the nebivolol effect in CHF patients reported; after 6 weeks period of treatment, plasma catecholamine remained unchanged at rest and during exercise [25]. Ayers et al. [26] reported that nebivolol has a neutral effect on IR in metabolic syndrome (Met S) patients. Apart from studies on carvedilol and nebivolol, De Groote and colleagues [27] investigated 3 months bisoprolol effect in patients with stable congestive heart failure; they reported EF% improvement with a significant decrease in plasma norepinephrine level.
The decrease of plasma norepinephrine with carvedilol found in our study could be explained by a sympathoinhibitory action through blocking peripheral B receptor [28]. Grundemar et al. [29] reported that carvedilol blocks B1, B2, and α1 adrenergic receptors at a higher dose. Also, it does not modulate B1 receptor (e.g., no upregulation or downregulation), thus, exerting much anti adrenergic properties compared to the selective B-blockers.
Although there was a significantly higher use of aldosterone antagonist (a drug known to improve insulin resistance in patients with chronic heart failure [30]) among the carvedilol group, however, this did not attenuate carvedilol effect on IR (e.g., carvedilol takes the upper hand).
Our result demonstrated normal serum PAI-1 level, with no significant differences between the two groups of our study population. According to some recent studies, the relation between PAI-1 and the Met S criteria needed for diagnosis may not always be straight forward and needs more study [31].
Nebivolol improved the insulin resistance-related variables (fasting glucose, fasting insulin, and HOMA-IR) while carvedilol was neutral. Meanwhile, carvedilol decreased plasma norepinephrine level while nebivolol was neutral. Lastly, both B-blockers improved the hemodynamics-related variables by the same extent. Nebivolol may be recommended as the B blocker of the first choice for non-ischemic cardiomyopathy heart failure patients complicated by insulin resistance; however, larger scaled prospective multicenter randomized trials are needed for confirming our favorable results.
Firstly, our sample size was relatively small; a larger scaled prospective multicenter randomized trial is needed. Secondly, long-term follow-ups are not studied.
All data and material of the research are available if requested.
Alanine aminotransferase
CABG:
CHF:
RAS blocker:
Renin-angiotensin system blocker
EGTA:
Ethylene-glycol-tetra acetic-acid
EF:
Ejection fraction
HB:
Heart block
HFrEF:
Heart failure with reduced ejection fraction
High-density lipoprotein
HOMA-IR:
Homeostasis model of assessment
HbA1c:
Glycosylated hemoglobin
IR:
NADPH:
NYHA:
New York Heart Association Classification
Plasminogen activator inhibitor
OPD:
SNS:
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Azevedo, E. R., Kubo, T., Mak, S., Al-Hesayen, A., Schofield, A., Allan, R., ... & Parker, J. D. . Nonselective versus selective β-adrenergic receptor blockade in congestive heart failure: differential effects on sympathetic activity. Circulation 2001 104(18), 2194-2199.
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Ogino K, Kinugasa Y, Kato M, Yamamoto K, Hisatome I, Anker SD, Doehner W (2014) Spironolactone, not furosemide, improved insulin resistance in patients with chronic heart failure. Int J Cardiol 171(3):398–403
Kodaman N, Aldrich MC, Sobota R et al (2016) Plasminogen activator inhibitor-1 and diagnosis of the metabolic syndrome in a West African population. J Am Heart Assoc 5(10):e003867
All authors declare that they have no financial or special source of funds.
Department of Cardiology, Faculty of Medicine, Zagazig University, Zagazig, Egypt
Yasser Gaber Metwally
Department of Internal Medicine, Faculty of Medicine, Cairo University, Cairo, Egypt
Heba Kamal Sedrak & Inass Fahiem Shaltout
Heba Kamal Sedrak
Inass Fahiem Shaltout
All authors contributed significantly in the research. Y.G.M. did actively the following steps: concept, design, definition of intellectual content, literature search, experimental studies, clinical studies, data acquisition, data analysis, statistical analysis, manuscript preparation, manuscript editing, manuscript review, guarantor, while H.K.S. did actively the following steps: design, definition of intellectual content, literature search, experimental studies, clinical studies, data analysis, manuscript preparation, manuscript editing, manuscript review. And lastly, I.F.S. did actively the following steps: design, definition of intellectual content, literature search, experimental studies, clinical studies, data analysis, statistical analysis, manuscript preparation, manuscript editing, manuscript review. All authors read and approved the final manuscript.
Correspondence to Yasser Gaber Metwally.
An informed written consent, in advance, had been given from all patients that was approved by the independent medical ethics of the University of Twente and the institutional review board of the participating centers (cardiology and internal medicine departments, Zagazig and Cairo faculty of medicine) (no reference number).
All authors declare that they have no competing interest.
Metwally, Y.G., Sedrak, H.K. & Shaltout, I.F. Effect of carvedilol versus nebivolol on insulin resistance among non-diabetic, non-ischemic cardiomyopathy with heart failure. Egypt Heart J 72, 63 (2020). https://doi.org/10.1186/s43044-020-00099-5


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Alesha MacPhail murder: Judge to consider lifting ban on naming teen who raped and killed six-year-old
By admin	 On feb 22, 2019
A boy who raped and murdered six-year-old Alesha MacPhail could be identified today.
The teenager, 16, is facing a life sentence after he was found guilty of killing the child while she visited her grandparents on holiday.
Judge Lord Matthews told him he had committed some of the "wickedest, most evil crimes this court has ever heard".
The boy cannot currently be identified for legal reasons as he is under 18.
Georgina Lochrane leaving the High Court in Glasgow, where a teenager was found guilty of the murder of her six year-old daughter (PA)
But the judge is set to consider an application from media outlets to lift the court order.
The teenager took Alesha from the bed where she was sleeping on the Isle of Bute on July 2 last year.
A picture among tributes near a house on Ardbeg Road on the Isle of Bute in Scotland, after the body of Alesha MacPhail was found in woodland (PA)
He inflicted horrific injuries before dumping her body in woodland.
A jury at the High Court in Glasgow took three hours to find the boy guilty unanimously, following a nine-day trial.
In a statement issued by Police Scotland, Alesha's family said: "We can't believe that we will never see our wee angel Alesha again. We miss her so much.
"We hope that the boy who took her from us is jailed for a long time because of what he has done to our family."
More about: | Alesha MacPhail | Courts
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Gary Raymond Cooper sentenced for string of driving offences
Sze 30, 2018
Nicholas Sparks Apologizes for Trying to Ban LGBTQ Club at…
jún 20, 2019
Two-Vehicle Accident On Stateline Road Caused Minor Injuries
Victim in Pendine murder investigation died from stab wound…

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Illinois governor signs 'radical' abortion expansion, but pro-life leaders predict backlash
June 13, 2019 CNA Daily News News Briefs 1 Print
Chicago, Ill., Jun 13, 2019 / 11:52 am (CNA).- Illinois' new abortion law is a "death penalty" for the unborn and will add to pro-life momentum across the U.S., critics said after Illinois Gov. J.B. Pritzker signed the bill into law on Wednesday.
"The bill Illinois lawmakers passed is so radical, they even went out of their way to repeal the state's ban on barbaric partial-birth abortions," charged Jill Stanek, an Illinois native and former nurse who is now the Susan B. Anthony List's national campaign chair.
"Americans of every political persuasion are appalled by these attempts to expand abortion on demand through the moment of birth and even infanticide, and that in turn is driving pro-life momentum around the country. There is no pride or glory in being the most extreme pro-abortion state in the nation," she said June 12.
The legislation, called the Reproductive Rights Act, passed the state's Senate by a vote of 34-20. It had passed the House in a 64-50 vote.
"In a time when too many states across the nation are taking a step backward, Illinois is taking a giant step forward for women's health," said Pritzker, a Democrat. "Today, we proudly proclaim that in this state, we trust women. And in Illinois, we guarantee as a fundamental right, a woman's right to choose."
Besides ending a ban on partial-birth abortion, the bill would remove regulations for abortion clinics and end required waiting periods to obtain an abortion. In addition, it would lift criminal penalties for performing abortions and would prevent any further state regulation of abortion.
The legislation would require all private health insurance plans to cover elective abortions. It would eliminate abortion reporting requirements as well as regulations requiring the investigation of maternal deaths due to abortion.
"The governor and the Democratic supermajorities who fast-tracked this legislation have created a new 'death penalty' in Illinois, with no possibility of appeal, for viable unborn preemies," said former Illinois State Rep. Peter Breen, who is now vice president and senior counsel for the Chicago-based Thomas More Society.
"This act is barbarous," he said. "Its definition of 'viability' expressly excludes many babies who today live and thrive when born premature," he added, noting that the law means that such unborn babies "now have zero legal rights or protections."
In a May 26 statement, the six bishops of Illinois had denounced the rush to push the legislation through at the end of the session, without releasing the bill's final text or vetting it through public hearings.
"The fundamental premise of the bill is flawed, and no amendment or tweak to the language will change the fact that it is designed to rob the vulnerable life in the womb of any trace of human dignity and value," they said.
According to Pritzker, the law codifies what was already case law due to court decisions. The state's partial-birth abortion ban, which became law in 1997, has since 2001 been under a permanent injunction from the Seventh Circuit Court of Appeals.
Pro-abortion rights advocates fear new Supreme Court decisions on abortion could overturn or greatly modify precedents in decisions like the 1973 decision Roe v. Wade. They have worked to ensure permissive abortion legislation in many states, including New York.
Some of the proposed laws, such as one in Virginia, led to controversy over whether such laws would permit abortion up to birth and would encourage authorities to turn a blind eye to the deaths of babies who survive abortion attempts.
Pro-life advocates, for their part, have sought to pass strong restrictions on abortion, hoping to expand legal protection for the unborn. Legislation barring abortion based on when an unborn child has a detectible heartbeat, about six to eight weeks after conception, has become national news with special focus on Alabama's law.
"While a growing number of states are working to advance popular pro-life laws, Illinois is trying to outdo New York's abortion extremism – and unborn children and their mothers will pay the price," Stanek said June 12.
Breen characterized the Illinois law as "the most radical sweeping pro-abortion measure in America." It would make Illinois an "abortion destination" for the country and is among "the most extremely permissive abortion laws of any state in the nation."
The law's creation of a "fundamental right" to have an abortion and to "make autonomous decisions about how to exercise that right," in Breen's view, mean the legislature and the governor have made abortion "the principal and primary right in Illinois, above all others."
In the wake of its passage, Cardinal Blase Cupich of Chicago said the vote "marks a sad moment in our history as a State."
The six Catholic bishops of the Catholic Conference of Illinois issued a joint statement against the legislation in February. The Catholic conference issued statements after it passed the state House of Representatives and the Senate.
Previous versions of the bill which were not passed into law included provisions that allowed non-physicians to perform abortions, removed conscience protections for health care personnel who object to abortion, and repealed parental notification requirements for minors receiving abortions.
On June 2 Bishop Thomas J. Paprocki said that Illinois Senate President John Cullerton and Speaker of the House Michael J. Madigan may not be admitted to Holy Communion within his diocese, because of their work to pass the state Reproductive Health Act.
"These persons may be readmitted to Holy Communion only after they have truly repented these grave sins and furthermore have made suitable reparation for damages and scandal, or at least have seriously promised to do so, as determined in my judgment or in the judgment of their diocesan bishop in consultation with me or my successor," he said.
The bishop also directed the Catholic legislators who have voted for legislation promoting abortion should not present themselves to receive Holy Communion until they have first gone to confession.
Paprocki said that he issued the decree to encourage conversion.
Feminists, Catholics both find reasons to oppose NY paid surrogacy bill
USCCB passes three measures in response to abuse crisis
DiNardo denies mishandling priest abuse case and confession allegations
June 5, 2019 CNA Daily News 0
Houston, Texas, Jun 5, 2019 / 05:06 pm (CNA).- The Archdiocese of Galveston-Houston disputed reports that Cardinal Daniel DiNardo mishandled a sexual abuse claim against a priest, and denied that the archdiocese had ever received reports that the accus… […]
The 'dire' border crisis continues as federal funds run out fast
June 21, 2019 CNA Daily News 0
Washington D.C., Jun 21, 2019 / 04:00 pm (CNA).- Amid of a surge of migrants, many of them minors, seeking to cross the U.S.-Mexico border, federal officials have called for emergency funding to address a growing humanitarian crisis. While reports diff… […]
'Safe injection site' denounced as false solution to Philadelphia drug problem
November 3, 2019 CNA Daily News 0
Philadelphia, Pa., Nov 3, 2019 / 04:44 pm (CNA).- A proposal to create a supervised injection site in Philadelphia has drawn criticism from the local archbishop and others who say resources to fight addiction should focus on full and authentic healing…. […]
TERENCE MCMANUS
On more and more fronts the battle is being joined – finally.
Grace a Dieu.
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The Pope is currently working on third part of "Jesus of Nazareth"
Carl E. Olson July 14, 2012 0
The Vatican Insider reports that Benedict XVI is working on the third volume of his Jesus of Nazareth books whie he is vacationing at Castel Gandolfo: The Pope arrived just last Tuesday at Castel Gandolfo, […]


text:
Aachen: First To Fall
Operation TyphoonMatanikau (Guadalcanal)
Back to: WW2
DG Folio Series
Theme: WW2
Before October 1944, no large German city had been directly assaulted by any Allied army. German soldiers were continuing to fight stubbornly throughout Europe, even after Germany's defeat became a certainty; so US commanders had every reason to worry resistance on German soil would be tenacious. In the city of Aachen itself, the street fighting was expected to be severe, just as it had been in other hard-fought cities. The situation along the border itself was even worse; the infamous West Wall loomed in front of Aachen, enclosing the city with miles of concrete bunkers, casemates and "dragon's teeth." The sense of foreboding among the GIs assigned to the attack, as well as their commanding generals, was evident and warranted.
Aachen utilizes the new Fire & Movement combat system that's designed so players can augment their units with "support fire" during the course of the turns. From mortars to fighter-bombers, units can receive support assets to engage enemy positions and formations, allowing combat to develop at all levels. A single recon battalion, for example — perhaps supported by anti-tank guns — could be tasked to assault a lone enemy regiment of engineers defending a road junction. As that attack gets underway, however, the recon battalion may find itself strafed by enemy fighter-bombers. More support will be necessary to take the road junction, but assets are limited.
In Aachen, the attritional design of the new Combat Results Table simulates the true nature of battles in Europe. Units are typically two-sided formations that can incur casualties, accurately replicating the realities of combat and the high losses sustained by both sides during the actual fighting in Aachen. Winning the battle is thus a matter of maneuver, firepower and asset management.
Game Contents:
17 x 22" (43 x 56 cm) terrain map
120 die-cut counters
One Standard Rules booklet for this series
One Exclusive Rules booklet for this title
Level: Battalion
Hex: 2 miles (3.2 km)


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Yesterday, the July corn contract closed 4 cents lower settling at $3.77, and the December contract was 3 ½ cents lower closing at $3.95 ½. Corn traded higher yesterday morning but turned lower when an updated forecast came out with soaking rains for the last part of June throughout the Midwest. EIA weekly ethanol report came out yesterday with production down for the 2nd week. Trade is becoming concerned that domestic gasoline usage, lowest in 6 weeks, is beginning to effect ethanol demand.
The July bean contract closed ¾ cent lower yesterday settling at $9.31 ¾, and the November contract was unchanged on the day settling at $9.39. Beans were trading higher for most of the morning but followed corn and wheat's descent. Brazilian ports are progressing at a record pace exporting beans, up 5 MMT from last year, putting additional pressure on beans. Two reports out today are the weekly export sales and the NOPA crush report, weekly export sales are expected between 300,000 and 400,000 MT. The NOPA Crush report is expected to be disappointing at 143 mln bushels, well behind last year's 152 min bushels.
Corn and beans are both down on the overnight. The dollar is a little stronger after the Fed announced raising the key interest rate .25 points to 1.25%. Crude is weaker as gasoline demand is down.


text:
Le elezioni europee del 2019 in Slovenia si sono tenute domenica 26 maggio per eleggere gli 8 membri del Parlamento europeo spettanti alla Slovenia.

Risultati

Collegamenti esterni

Slovenia
2019

redpajama_set_name: RedPajamaWikipedia


A personal loan is a type of loan that falls under the umbrella of unsecured loans. A personal loan is handy to get instant cash that allows you to use the funds as you like. A personal loan does not require you to pledge any property or valuables as security. The repayment time span of personal loans usually ranges from weeks to five years depending on the policy of the credit institution and most of the times there is a fixed amount of repayment installment with equal intervals of time.
How many times have you taken a loan?
Which type of loans did you take in the past?
How many numbers of times the did you delay the payment?
Is there any default made in the previous history?
Information about your income is necessary for assessing whether you can repay the loan amount or not.
If you have a steady source of income and maintain a positive credit rating or history, you'll be eligible for getting a personal loan.
When you apply for a loan under a credit line, the bank or credit union calculates your credit limit based on your total average monthly income. After determining your credit limit, the bank approves the loan amount and transfers it to a loan account. You use the money whenever you need it instead of withdrawing the whole amount.
A personal credit line is very similar to a credit card. However, it allows you to withdraw the cash from the bank directly. The bank generates a monthly bill with the minimum and total amount payable by you. You have a flexible payment option whether to repay the minimum amount of the bill or repay more than that amount. There is no fixed schedule of making repayment installments; a borrower can deposit the amount in the repayment account whenever you have the money during the month in addition to the minimum payment.
One of the best benefits of a credit line is that upon repayment of the loan, you're already approved for that amount. There is no need to get approval or apply for a credit line again. Another essential feature of a credit line is that the interest is charged on the used amount of money instead of the total approved loan.
When a borrower applies for a personal loan, if you are approved, the loan is transferred to you. The whole amount of the loan is handed over to you along with the schedule of monthly repayments. The amount of the installment is usually a fixed amount over a set time. The terms regarding your repayment amount, the rate of interest and the length of the loan is predetermined at the time of applying for the personal loan between you and the lender.
A borrower who has an excellent credit rating and steady source of income can get the loan by signing the loan papers. Therefore a personal loan is also called a signature loan or consumer loan. Personal loans are unsecured loans and expose the lender to a higher risk and usually have a higher rate of interest as compared to secured loans.
Personal loans are not specific or special purpose loans like home loans, car loans or education loans. Personal loans are used for meeting personal needs.
Before applying for a personal loan, it is better to calculate the actual amount of funds you need to meet the specific situation. Only that amount should be borrowed from the credit institutions even if your credit rating allows you a higher loan amount.
As personal loans are designed to meet the instant need of cash, the loan processing is very speedy, and the loan will be available to you in a very short span of time as compared to other types of secured loans. Don't be enticed to increase your loan amount.
Credit market research is necessary regarding the interest rates while applying for a personal loan. Interest rates vary from institution to institution. Compare the interest rates between banks and other financial institutions. Find the cheapest rate you can for your loan. Interest rates have a huge impact not only on the cost of obtaining the loan but also increase the monthly repayment installment and can disturb your cash flow. A lower rate of interest is better in all aspects of your loan.
When you are approved for the loan, all you need is to sign a document that contains the terms and conditions of the loan. That's why an unsecured personal loan is also known as a signature loan. At the time of applying for a personal loan, it's better to acquire the contract agreement in advance to read and understand the prerequisites for the loan.
Most of the time, some of the costs like processing charges and other hidden financial fees associated with the loan would be negotiated with the bank only if you know about them before applying for a personal loan. In other words, applying for a loan quickly without reading and considering the impact of the terms can increase the cost of funds.
Determine Which is Better: Variable or Fixed Interest Rates?
Some money lenders offer the option to opt interest rate at variable or fixed rate.
The movement of the interest rate varies according to the market conditions if there is a rise in interest rates of the market then the loan interest rate will also rise and in case of fall in the rates, personal loan installment will also fall.
The rate of the interest is decided before signing the loan agreement, and the interest rate remains unchanged irrespective of the market fluctuation.
So, the decision of which interest rate is also critical to receive the lowest cost to finance and minimize the monthly installment fee. At the time of applying for a personal loan, consider the previous history of the interest rates. Assessing the interest market trends will be beneficial.
Most of the time people apply for personal loans to consolidate different loans into one loan. They are making two or three payments during the month. One of the best uses of a personal loan is that you find a cheap source of funding. You can combine all your other loans and pay them with one fixed installment that will be payable monthly.
Getting a personal loan is very easy now these days as so many private companies, banks and trade unions offer this type of loan. All you need is to not hurt your credit score by paying your bills on time. Selecting a lender with terms that best suit your financing needs and have the lowest rate is critical. A personal loan is a convenient way to respond to unexpected or emergency financing requirements, but using it wisely is also very essential to avoid the burden of loan repayment.
Getting a personal loan for bad credit.
Loans with no credit checks.
Title loan instead of standard bank loan.
Whatever three reasons you wrote down, we're willing to bet none of them match the three we gave you.
Using installment loans to fix bad credit is a perfectly valid and responsible practice of borrowing money, and none of the large, standard banks will approve a loan for this purpose. Seems counter-intuitive, doesn't it? Fixing your credit would open doors for you to borrow from banks, so you would think they would provide this service.
Getting no credit check loans are simply not possible in any of the conventional lending banks.
A title loan for smaller loan purposes is often easier to obtain and quicker, with smaller and shorter terms than a standard loan through a large bank. Where you can borrow several thousand dollars for a title loan, most large banks will not loan any amount under $20,000. And some of them penalize you for paying off early!
Come see CASH 1 if any of these three reasons to use our services might apply to you.


Pittsburgh Steelers quarterback Ben Roethlisberger and running back James Conner both find themselves on the brink of history tonight in their matchup with the Carolina Panthers.
Ironically enough, the Steelers are now just one game away from reaching a statistical milestone that involves the tandem success of their quarterback and running back without the likes of Le'Veon Bell.
Five straight games with a 250-yard passer and a 100-yard rusher would be quite an impressive feat to add to another fantastic offensive season for the Steelers, especially one that's featured Conner's success in Bell's place.
And that's not the only record that Roethlisberger can reach tonight either. Roethlisberger could become the sixth quarterback in NFL history to throw for 200 touchdowns at home, needing just two against the Panthers defense tonight in Pittsburgh.
#BensDay#Steelers QB Ben Roethlisberger (@_BigBen7) has thrown 198 touchdown passes in his regular-season career in games @heinzfield.
Tonight could be a very special night for Big Ben, Conner, and Pittsburgh together, not to mention one of the more exciting Thursday night matchups we've seen all season.


text:
Fisher's new hypothesis
G. F. Becker
American Journal of Science August 1893, s3-46 (272) 137-139; DOI: https://doi.org/10.2475/ajs.s3-46.272.137
The basin of the Gulf of Mexico
J. E. Hilgard
American Journal of Science April 1881, s3-21 (124) 288-291; DOI: https://doi.org/10.2475/ajs.s3-21.124.288
Remarks on general ocean circulation
Wyville Thomson
American Journal of Science November 1878, s3-16 (95) 349-360; DOI: https://doi.org/10.2475/ajs.s3-16.95.349
Underwater oceanic temperature
G. E. Belknap
American Journal of Science January 1878, s3-15 (85) 27-29; DOI: https://doi.org/10.2475/ajs.s3-15.85.27
On some rocks and other dredgings from the Gulf Stream
S. P. Sharples
American Journal of Science March 1871, s3-1 (3) 168-171; DOI: https://doi.org/10.2475/ajs.s3-1.3.168
Gulf stream explorations; third memoir; distribution of temperature in the water of the Florida Channel and Straits
A. D. Bache
American Journal of Science March 1860, s2-29 (86) 199-205; DOI: https://doi.org/10.2475/ajs.s2-29.86.199


With Raleigh being our state's capital, it is not surprising how many homes and apartments have been constructed within its borders and surrounding areas. As a result, our SERVPRO team remains prepared 24/7 for emergencies like water loss incidents that could occur and quickly spread to damage these structures. From standing water to saturation of construction materials, addressing the negative impacts of Raleigh area water damage emergencies should happen as quickly as possible.
Flooding and water emergencies don't wait for regular business hours and neither do we. We provide emergency water restoration services 24 hours a day, 7 days a week – including all holidays. Raleigh residents can expect an immediate response time, day or night.
Immediate action is crucial when dealing with water damage. With over 1,700 U.S. and Canadian Franchise locations, we are strategically positioned to be faster to any-sized water emergency. Raleigh residents can expect an immediate response day or night.
We live and work in this community too; we might even be neighbors. As a locally owned and operated business, SERVPRO of North Raleigh & Wake Forest is close by and ready to respond to your flood or water damage emergency. We are proud to be an active member of the Raleigh community and want to do our part to make our community the best it can be.


always a good crowd and a good time when county line is here.show starts @ 8:30 p.m.
We had a big crowd and a great time last time they played here. Let's do it all over again.
county line band playing for the blue marlyns 1st annual poker run.dedicated to our dear friend t.d. r.i.p. starts @ 9:00 a.m. county line band starts @ 3:00.


text:
El Rally Caminos del Inca del 2015 Eduardo Dibós Silva, es la 45.ª edición de la carrera de rally más tradicional e importante dentro del territorio peruano, se está realizando entre el 10 y 18 de octubre de este año. Esta edición se rinde homenaje a don Eduardo Dibós Silva, triple campeón del torneo durante los años 2000. 2001 y 2002; además de presidente del Automóvil Club Peruano, quien recientemente falleció. En esta edición el recorrido en general vuelve a su itinerario original (Lima - Huancayo  - Ayacucho - Cuzco - Arequipa y Lima) modificando cambios en torno al punto de partida inicial, siendo la localidad de Huaral, ciudad ubicada al norte de Lima, como punto de inicio de la carrera, agregando con ello un nuevo trazado en la primera etapa hacia la ciudad de Huancayo, además de modifiaciones en la segunda etapa (Huancayo - Ayacucho). La organización del evento está a cargo del Automóvil Club Peruano, que junto al patrocinio de empresas privadas se encarga de la logística general y premiación a los ganadores.

Etapas

<small>

Resultados por etapas

Clasificaciones finales
- Diez primeros clasificados en todas las categorías en competencia.

Referencias

Caminos del Inca
Deporte en Perú en 2015


These LED 10W bayonet cap lamps by Lyco will deliver reduced maintenance and running costs, thanks to the lower consumption and high life expectancy, when compared with the 60W incandescent equivalent.
Due to high demand we are currently out of stock of this item. Orders will be delivered middle of May. Alternatively we recommend item code 12070.
As expected , a little larger than some bulbs though.
Goods do work. Not yet in regular use.


text:
Andrew Fiouzi
Andrew Fiouzi is an editor at dot.LA. He was previously a features writer at MEL Magazine where he covered masculinity, tech and true crime. His work has been featured in the Los Angeles Times, Long Reads and Vice, among other publications.
'No Swiping, No Profiles, No DMs': 222 Wants to Serve Gen Z Experiences Based on Serendipity
image by 222
Midway through dinner at a West Hollywood restaurant, Arman Roshannai, the 21-year old CTO of 222 cites 19th century French polymath Pierre-Simon Laplace's demon. Or, rather, the Frenchman's theory of destiny. As Roshannai explains, LaPlace thought that if someone (the demon) knows the precise location and momentum of every atom in the universe, their past and future values for any given time can be calculated from the laws of mechanics. Freewill, Laplace would say, is an illusion.
How did we get to Laplace? Roshannai made a joke about 222 being his demon after I suggested he's Dr. Frankenstein.
"Don't mention that in the article," Roshannai says. He's mostly joking.
But how could I not? 222 is a demon caste from human brain mimicry. But unlike the other demons — consumer predictability, metaverse, surveillance — 222 is offering salvation.
The idea for 222 began with a simple theory: "Meeting people through chance encounters, being at a bar, seeing someone wearing a shirt of a band you like and striking up a conversation just felt much better than getting a follow request on Instagram," says Danial Hashemi, the 21-year-old COO.
To test it, Roshannai and Hashemi began to host events at Keyan Kazemian's house—the 23-year-old CEO of 222.
"We would beg our friends who didn't know each other to come to Keyan's backyard where he lives in Orange County," says Hashemi. "We cooked pasta and served wine." They also had their friends fill out a personality survey that they then used to determine who should sit at which table at subsequent dinners.
People kept coming back. Some people became best friends. Others started dating. And what began as a college research project bloomed into an AI company. "No swiping, no profiles, no dms, just say yes and find the people and places that best match your personality," says Hashemi.
Sound cool? The table next to ours thinks so. They're one of a smattering of four-to-eight person cliques at the West Hollywood restaurant who have been synthesized to have a good time. And by the looks on their faces, bright-eyed and full of expression, 222 is working.
To sign up, you have to be between 18 and 27. For now, 222, is targeting Gen Z. The app, I'm told, is coming soon but until then you enter your phone number on 222's website before being directed to 30-some odd questions that include:
"Would you rather watch an arthouse or mainstream blockbuster?"
"Would you rather go clubbing or have a daytime picnic?"
"Would you rather listen to Tchaikovsky or Megan Thee Stallion?"
Potential members also have to rate how strongly they agree or disagree with statements like:
"I would go to space if there's a chance I wouldn't come back."
"Humans should make an active effort to curb the emission of greenhouse gasses."
"Humans are born with an innate purpose."
The survey also includes a self-assessment of your drug habits and at one point you have to rate your own attractiveness on a scale between one and 10. The goal is to provide the AI with enough data points for it to determine which of the 16 categories your personality falls into.
"Once you get your personality type, you wait until we have an experience," Hashemi says.
For now, 222 experiences are held every other week. Members who are selected by the AI engine to attend the dinner portion of the evening pay $2.22. Those who aren't selected for the dinner portion of the experience can still, if they choose, attend the post-dinner venue.
The way the AI determines compatibility is a bit of a mystery.
"The AI picks up on these social trends itself," says Roshannai. "It may notice that similarity is a great indicator of compatibility, or find other underlying patterns that we didn't even know existed."
Based on feedback from real-life interactions, he continues, "we certainly can and will do some tinkering with what we feed the model." But ultimately, the model itself will start learning what prompts have weight and which questions are best used to predict meaningful connections.
According to Kazemian, "Do you think comedy is becoming too politically correct?" Has been particularly successful in determining compatibility. Political leanings less so.
Back at the restaurant, Kazemian pulls out his laptop, scans the room like a spy, taps a few keys on the keyboard and runs a script. The program sends participating 222 members a text message with info for the post-dining venue.
Tonight, the venue is a rooftop lounge within walking distance of the restaurant and with a 180-degree view overlooking the city. Hashemi confirms there's a section designated for 222 members. While we're standing around the tables, Kazemian's girlfriend dares Roshannai to go talk to a girl. He does. Pays her a compliment on her dress "and it worked," Roshannai exclaims. The look on his face is a familiar one, it's the look of excitement spawning from serendipity. It may seem like typical human behavior but increasingly, it's not.
Every trend report suggests young people just don't care about being in the physical world anymore. Tech companies are obsessed with trying to create increasingly immersive online spaces to hang out in. The average young person spends half their waking life staring into a screen. The office is dead. Third spaces are increasingly scarce. The loneliest generation in the history of the world keeps getting lonelier.
"Have you read Robert Putnam's book "Bowling Alone?" Hashemi asks me. "One of the slides on our pitch deck literally says we're anti-Metaverse."
Not long after our arrival, the trio begins to notice familiar faces from the restaurant pour in. Hashemi says that as their member base has grown steadily at a rate of 30% per month since 222's inception, it's increasingly difficult to differentiate who's been sent by 222 and who hasn't. Based on the RSVPs, of the nearly 40 people who attended the dinner portion of the evening, only four or five replied that they wouldn't attend the post-dinner venue. Which is to say, 222's success rate, at least for this evening is roughly 90%.
The use cases for this technology, Kazemian says, are myriad: choosing seats on airplanes, selecting roommates, providing venues with information about their patrons' likes/dislikes to best curate an unforgettable evening. But the goal, the same one that inspired those backyard dinners, remains the same: Veer people back towards the physical world. Incite meaningful connections IRL. Use the demon to fight the demons.
Feeling Streaming FOMO? This LA Startup Has a Solution - dot.LA ›
Meet the Dating Apps Launched During the Pandemic - dot.LA ›
Kippo, a Dating App For Gamers, Enters the Metaverse - dot.LA ›
Meet Sunroom, a New App That Wants to Empower Women and ... ›
UCLA's MNN Project Is Rapidly Advancing AI As We Know It - dot.LA ›
artificial intelligence222dating apps
entertainment tech
Hollywood Decentralized: Meet the Artists Using AI to Dethrone Tinseltown
Photo by Martin Jernberg on Unsplash
When I first spoke to Jamil Mehdaoui, an architect and former Oculus employee, he'd just returned to Paris from a weeklong pilgrimage into the future of movie making. Mehdaoui describes his work as "a collaborative process" between himself and the artificial intelligence that brings dream worlds to life with just a few key words. On Zoom, he occasionally appeared frustrated. Eager. Unsure. Hopeful.
Like millions across the world, Mehdaoui is experimenting with Midjourney, a text to image program that generates images from a repository of data that spans the entire history of art and human existence as it's cached online. Unlike millions, Mehdaoui is attempting to use this tool to make the first ever AI-generated feature film. And appropriately, he's chosen to remake Pinocchio — the story of the first ever artificial boy.
Like the more well-known text to image AI tool — DALL-E — Midjourney's output depends on art that's already been made and photos already taken. But since Midjourney can't read Mehdaoui's mind (yet), it takes time to find the right levers to pull in order to get the AI to do what he wants it to.
\u201cPinocchio AI film will be a serie of 7, all generated by AI, produced by @theculturedao @AiFairytales\u201d
— jamil_M (@jamil_M) 1664210181
For example, Mehdaoui was initially focused on prompting the AI to generate images of a boy fashioned from gnarled, raw wood. The troubles were myriad. First, Mehdaoui says, "The moment you ask the AI for Pinocchio, you lose control. It puts you in Disney's hands." Meaning the images the AI generated were often too familiar. Too recognizable. The other issue was getting the AI to see or rather interpret beyond such a generic descriptor as "boy that looks like a log." So, for days, Mehdaoui tinkered with his prompts until his fragmented vision, the one cradled only in his mind, came to life, authored by artificial intelligence.
As the director of the movie, Mehdaoui has full creative control over his AI-generated Pinocchio. But there's no studio backing his project. Instead, he's one of 750 artists, architects, AI engineers, storytellers, animators, game designers, interoperability explorers and business folks who have joined together to dethrone Hollywood.
The Culture DAO is a "metaverse guild" assembled by Edward Saatchi, the chief executive officer (CEO) of Fable, an artificial intelligence-powered virtual being company, and the founder of Oculus Story Studio. Members of the DAO include current and former storytellers from Pixar, Lucasilm and Oculus, many of whom are currently working on an amuse-bouche of fairy tales, horror flicks, animations and live-action shorts.
\u201c.@StableDiffusion Img2Img x #ebsynth Creature Test\n\n#stablediffusion #AIart\u201d
— Scott Lighthiser (@Scott Lighthiser) 1663474460
Saatchi assembled the guild out of a concern that the most zealous artists interested in AI might waste too much time playing around with new features. "You could go two years, making very small demos and creating nothing substantial that's going to last for 100 years," he says. And since Saatchi believes AI-generated media is the beginning of a new art form, it was important, he says, to "encourage artists to find personal stories they want to tell that are empowered by AI."
One of those artists is Scott Lighthiser — a VFX artist who studied production in college and has been experimenting with filmmaking techniques ever since. "But when Stable Diffusion [another AI powered text to image model] was released I could generate super realistic cinematic images," he says.
Unlike Mehdaoui, who's using AI text to image programs to animate a feature film, Lighthiser is working iteratively on developing short live-action clips. He's posted a few of these videos on Twitter. The response has largely been one of shock. It seems few people expected the AI to be this good, this quickly. The first video shows how Stable Diffusion can add a layer that further immerses Lighthiser's own face into a purple-skinned character. The second flaunts Stable Diffusion's ability to quickly disguise Lighthiser's body, rendering variations of a hissing monster. That Lighthiser was able to create these short clips on his own, a week apart, is part and parcel of how the Culture DAO plans to take on Hollywood.
"Being able to make animated movies not in seven years but in several weeks or being able to make live-action, effect heavy, content not in several years with hundreds of millions of dollars but in several weeks and with thousands of dollars, I think is going to massively democratize what's possible," says Edward Saatchi.Their recent progress aside, Saatchi's proposition to decentralize Hollywood by democratizing access to the resources of a studio is still in its infancy. The Culture DAO's current slate of content is mainly focused on horror and animation. Horror because audience expectations around having stars and a big budget are lower and the AI program offers some really creepy effects. And animation because the output is more technically suited to AI text-to-image programs.
AI Pinnochio movie poster Image courtesy of Jamil Mehdaoui
But even in this time of great daydreams and ambition, not everything is going according to the plan. Since our initial conversation, Mehdaoui has already had to parcel his concept for the first feature length AI film into seven serialized episodes. And though Lighthiser's short clips suggest a light at the end of the tunnel, they're far from a finished product. "If we're talking about shooting an empty room and processing it to look like a 19th century Victorian mansion, I don't think we're there yet but probably pretty close," says Lighthiser. "I think using AI in conjunction with LED Volume technology has the potential to be extremely powerful. But eventually you'd want to be able to take your phone out, point your camera at a barn and say 'turn the barn into a spaceship' and it renders it in real time."
Naturally, there will always be detractors who argue any AI-generated art is merely "visual gibberish." In fairness, much of what appears on Twitter does appear that way. Others critics have genuine ethics and copyright concerns. Like—what happens if everyone's AI art steals from the same artist?
But Saatchi says these concerns are the growing pains at the frontier of a new artform. This moment, he says, is like the early days of Pixar. Back when the technology company failed to sell computer hardware and pivoted toward creating computer-animated shorts.
\u201c\ud83e\uddc2\u201d
— SALT (@SALT) 1655236583
If even half of what the Culture DAO is promising becomes reality, Hollywood's place as the entertainment capital of the world is imperiled. Most of the members of the DAO are spread all across the world. To some degree, this reckoning is already underway: In August Belfast-based composer and computer artist Glenn Marshall won the Jury Award at the Cannes Short Film Festival for his AI film "The Crow."
More recently, Fabian Seltzer, co-founder of the Culture DAO along with Saatchi, was in the news for his AI-generated, choose-your-own-adventure movie fashioned after 70s-era sci-fi films. Both projects were essentially created out of an individual's home office.
"What I saw at Pixar—what I see in VFX— is that brilliant people who might not be entrepreneurial enough to start up their own studio, are being crushed in their creativity because it's such a factory system," says Saatchi. "It's shifted to being about cost management and the creativity has gone down and these projects require so many people and so many resources."
With AI, however, the number of people it takes and the amount of money required to make a Pixar-quality film doesn't just have the potential to be cut in half, it might well be a fraction of the $200 million budgeted to produce many of these movies.
Saatchi's message to the folks in Hollywood? "It's time to get out and develop your own project."
Creatives Fear AI Generated Art Is Coming For Their Jobs - dot.LA ›
Art Created By Artificial Intelligence Can't Be Copyrighted - dot.LA ›
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Midjourney ›
Midjourney - Wikipedia ›
Pinocchio - Wikipedia ›
artificial intelligencehollywooddall-eentertainment tech
influencer economy
The Existential Crisis Plaguing Tech's Cohabitation Incubators
In 2021, dot.LA reported on the invasion of the startup live-in incubator. "In the Hollywood Hills, a collective started by two twenty-seven year-old entrepreneurs is helping seed-stage companies land funds and build up their products," wrote Katherin Abando. "Across town, a roving launch house focuses on building biotech entrepreneurs. Another is trying to foster breakthrough products in augmented reality."
Fast forward a year. The collab house model—which often touts itself as an educational program for tech entrepreneurs to live together and develop their companies—is facing an existential crisis, with at least one of the examples lauded in the article facing multiple allegations of fostering a culture that led to sexual assault, harassment and in one case, retaliation against a member of the house.
The distinction between Launch House and other live-incubators has been well described. In 2021, dot.LA reported that unlike veteran accelerators like Y Combinator, Launch House founders Jacob Peters, Michael Houck, and Brett Goldstein weren't promising entrepreneurs any investment. Instead, the draw was, "schmoozing, advice and social media exposure." And their idea was based on Peters' belief that, "Universities are no longer going to be the aggregators of great talent. It's going to be small, niche communities that start in houses."
If that's going to be the case however, there needs to be a serious reconsideration of how the collab-house model operates when the heat is on. Earlier this month, Vox released an investigation into Launch House, a "professional social club" for tech founders, which among other activities, hosts members at a luxury property in Beverly Hills. Since that report, some existing investors in the startup and its venture fund have issued public statements supporting the alleged victims and denouncing the alleged behavior of Launch House. Others have taken the stance that the reporting of the story itself was exploitative, blaming the media for its "handling" of the news was itself insensitive.
Launch House, meanwhile, confirmed to TechCrunch via spokesperson that it is initiating its own independent, third-party investigation. Company CEO Brett Goldstein published a public memo in response to the allegations in which he stated that claims in the Vox story pertain "to a period over a year ago when we were a very different company."
This isn't the first time Launch House has faced complaints of workplace misconduct. Late last year, Business Insider reported about a "wild party" at the Launch House mansion in May 2021 as well as a COVID outbreak the year before.
Should anyone be surprised that a tech incubator full of young people living and working under the same roof, with dreams of being tech entrepreneurs, is prone to cultivating an unsafe workplace environment?
In 2017, Y Combinator was in the news for similar indiscretions. At the time, the incubator—known for launching Airbnb, Coinbase, DoorDash, Dropbox, Reddit and Twitch—was facing their own set of allegations of sexual harassment in the workplace. The startup ostensibly dealt with the situation by issuing apologies and having two high-profile venture capital investors resign. Nonetheless, a year later, according to a survey by Y combinator, one in five female founders who passed through the influential Silicon Valley startup incubator still reported having been sexually harassed or assaulted by investors.
Nearly half a decade later the tech incubator model is still suffering from the same issues that might be obvious to anyone who looked beyond the promise of community. Despite the various cautionary tales of toxic tech startups whose founders end up being played by Joseph Gordon-Levitt, Jared Leto or Amanda Seyfried, many of these incubators have yet to take the very basic step in becoming a legitimate enterprise. Live-in incubators aren't hiring live-in Human Resource departments…or any at all. And that's a big problem.
Chien-Chi Tseng is a Collegiate Associate Professor of Technology Entrepreneurship at Virginia Tech who used to develop incubation centers across Taiwan university campuses. According to Tseng, the incubator model should adopt an approach to HR no different from a standard company.
"Like the clients it serves, the incubator must be based on a solid customer need and provide a strong value proposition," Tseng told dot.LA. "The common thread among all the successful incubators is that they are run as businesses with the customer being the companies they serve." In the case of Launch House, that's the young individuals who are trying to create a successful startup who are also living under their roof.he live-in incubator, Tseng believes, warrants a paradigm shift in how it thinks (or more often, doesn't) about HR. department.
"To better approach the work format of live-in incubators, HR teams cannot decide their success based on a single parameter," Tseng told dot.LA, one that takes into account a "narrow but diverse set of metrics." Those metrics can range from an incubator's financial health to the number of acquisitions and IPOs; the support provided to its members both in the form of funding from investors to more ephemeral benchmarks, like mentorship engagement. It also needs to be able to swiftly address a myriad of new issues that stem specifically from having colleagues living together: screening applicants not just on the strength of their pitch, but their background checks. Due diligence is a foundational necessity in this process, yet seems to be a low priority for young incubators…until they find themselves in hot water.
To that end, Launch House promised during a private town hall that they are building an industry-leading safety and security program for co-living experiences. The details of the program, however, have yet to be divulged.
With that said, Launch House is hardly the only live-in incubator house reckoning with issues arising from a co-living experience. More recently, a leaked contract from Hype House — one of the most famous and longest-running content houses in Los Angeles — revealed a series of extremely restrictive rules that participating influencers have to follow. "You're giving up all rights to any claims you have," said one Los Angeles based lawyer who has represented influencers and others in the entertainment industry. "Everything. All known and unknown future claims, which is excessive." Far from investing in human resources, Hype House invested in the opposite: lawyers and publicists. This sends a message to the community that optics are more important than fixing systemic issues.
A request for comment sent to four different LA-based live-incubators asking how they're triaging their approach to HR received no responses.
Currently, the live-in incubator environment makes up a small fraction of Los Angeles tech entrepreneurship. As Vox noted, "Programs like Launch House, which often require members to pack their bags and move to a new city with just a few weeks' notice, are only feasible for a very specific group of people: young, hungry digital nomads with the freedom to figure it out as they go along."
But that number is growing, propelled by a new generational ambition: over 30% of Gen Zers living in Los Angeles want to be influencers. With the rise of the "creator house" and an ever-expanding network of live-in startup options, there's every reason for the collab house model to consider a more robust approach to mitigating the dark side of building "community" in tech. Otherwise, the issues plaguing Launch House today will continue to be the industry standard.
Meet the LA Startup Houses Building Companies Through Co-Living ... ›
Launch House: Influencer Energy Meets Entrepreneurial Grit - dot.LA ›
Launch House holds private town hall, says investigation is ... ›
Launch House, a tech startup incubator, sold entrepreneurs on the ... ›
Launch House ›
hype houseinfluencer economylaunch housetiktoky combinator
Q&A: Former Head of Yeezy-Adidas Innovation Lab Shares His Journey To Create a Footwear Prototyping Lab


two sessions which conducted by two eminent speakers. The first session hold by Prof.
attempt to commit suicide in stressful situation.
icall organization which provides telephonic counseling sessions to all people who are in trauma.
certificates for attending this seminar.


Hey all, Monica speaking. One of the hardest questions to Google when applying to graduate school is how to write a statement of purpose. There is a lot of advice for how to apply to grad school in general, but science graduate applications are a different beast because of how formal they have to be. There's a particular art to selling yourself, in a based-on-my-work way, that's hard to capture.
One resource which I quite like is CMU's advice handout. This does a really good job of capturing what should go into a statement of purpose. This blog post also does a great job of telling you what you SHOULDN'T be writing. The statement of purpose is not a college application essay-- you're selling your ability to do research, not you as a person.
Given how difficult it is to find examples of essays, I've attached my two essays to Berkeley. One is a statement of purpose, which is the usual requirement to schools. Berkeley was the only one of my schools which also required a "personal history" essay-- and I actually think this might have been important in my admission, but at most schools you don't have the opportunity to write a document like this. Regardless, I'm making them both accessible as examples (Statement of Purpose, Personal History). I don't have a good sense of how these are different from other people's application materials, so take them with a grain of salt :).
However, there is good news! Though graduate essays are not often available (it's also considered a bit taboo to ask people for them), there is a marvelous website that collects essays for the NSF GRFP Fellowship. I highly recommend reading the essays under "Personal" on this website put together by Alex Lang (scroll to the bottom where the essay examples are), because these personal statements are almost exactly the style you want to use in your graduate applications. They might be leaning towards the too-personal end, but reading a bunch of these will let you get the gist of what your essays should look like.
I wrote similar essays for each graduate school I applied to, with a few paragraphs and sentences that were specific to each program. Make sure that for your main essay, you have professors-- preferably more than one professor-- read it, and the recommendation is always to start early since you'll likely need to go through several drafts and make major changes. Also have your friends read it, especially if you know people in graduate school. I personally am happy to read essays right now-- send me an email (see About page) and we can Google Doc it out.


text:
Imagining Futures: Imagination, Ltd.
by Elsa Sjunneson	in Uncanny Magazine Issue Forty | 1547 Words
When we're little, we are told that imagination has no bounds, that we are unlimited in what we can come up with. Every television show relies upon the suspension of disbelief that children are gifted with, and that suspension of disbelief is eroded or beaten out of us as we age. Every children's book allows for the fantasy of a child's imagination, but as we grow we are told that those fantasies are left to genres like sci-fi and fantasy. My partner has two children. Being immersed in the world of childlike imagination has gotten me to thinking about how we imagine, and how our imagination changes as we age.
The word genre becomes a bad word.
The world and what we believe it can be gets smaller.
Because society gets in the way.
That process of erosion starts in little ways—forgetting to say "yes, and" instead of "no" when a playmate tells you part of the story they want to tell with you. In the way the books you read go from being picture books with talking animals and trees, to being hidden away and shelved with the other genre books. What's the difference between The Princess in Black and Dealing with Dragons, which are shelved in general kidlit at my local bookstore, and Uprooted except that we assume children are accepting of all narratives? Isn't Where the Wild Things Are a monster story in a secondary world?
The erosion tells us what we are allowed to imagine outside of the gutters on the page. Unless we partake in the art of fanfiction, we're not asked to imagine outside the borders of what's on the page past childhood.
Science fiction and fantasy worldbuilding is an art in developing boundaries; we have to decide how things work, who lives somewhere, and what can happen in order for our stories to make sense. Audiences (and frequently gatekeepers in our industry) want answers to practical questions like "why can that dog talk" and "is Garfield a kaiju". They want to know if it's "realistic" for a blind character to perform certain activities.
But the idea of things "making sense" is a fundamentally grown-up sort of idea. "Making sense" also relies upon commonly understood ways of being. A non-disabled audience is less likely to accept the reality of a disabled life, whether or not it's accurate.
The world is so much messier than the sensible world gives us credit for.
When I watch movies or read books about science fictional worlds that don't feature disabled characters, I often imagine those folks on the sidelines of the story. Sometimes I imagine what their lives are like—not because I want to but because I have to. Disabled people aren't in the text, and are rarely in the subtext. When I imagine disabled characters, it is using my own mind, working off what the author has given me. We're rarely there, because non-disabled people have been taught not to think of us, and that includes removing us from their imaginations.
The erosion of my imagination has been in part in what questions I do not ask. I have learned not to ask where the disabled people are, because when I do, the inevitable answer is that we wouldn't be there at all. Curative culture demands that we accept cures for our broken bodies, and it tells non-disabled people that they should imagine that all disabled people have the internal narrative that something is wrong, that they must be fixed. But my internal monologue is rarely about what I need to fix, but about how my world fails me at every turn.
As adults, we contend with something called being "realistic." It isn't just in our real lives where we pay bills and rent that we are given little room to roam in our minds, but there are bounds to the world of story too. The imagined world is often gatekept by editors, marketing teams, casting departments and more in terms of what story is "believable" to a mainstream audience. The expectations game is fraught because what's realistic is ultimately policed by the dominant society. We don't see blind characters with nuanced vision, for example, because that's outside of the collective imagination (you should see what happens when people find out I can use Twitter!). This means that the non-disabled people of our collective imagination have made decisions about the disabled imagination, too.
Basically, when a disabled person says what they do (for real) or even what they want to do (as an imagined act) often non-disabled people will tell us we can't. That's a limit to our imaginations, and it affects the stories that gatekeepers will buy. It affects what we can have our characters do, too.
In writing, imagination is more or less our currency, it is what makes our industry work.
But when we start to tell each other—our audiences, ourselves—what's possible, when we start to lose suspension of disbelief in favor of what "makes sense" we're making definitive decisions not about what anyone can imagine, but about what the creator can. There are thousands of ways to tell the same story, yet the gatekeepers of publishing lay it at the feet of the mainstream audience as a reason to keep perspectives easily understood. Catering to the mainstream narrows what we imagine as a collective. So if you're a non-disabled author telling a story about the future and you can't imagine a disabled person in space…we just won't be there. If you can't imagine Black people in historical settings…they won't be there either.
Bias is often running the show when it comes to what can be believed. A clear narrative to a mainstream audience may be untrue for a marginalized author. For example, it doesn't make sense to a hearing audience why a Deaf character would choose not to wear hearing aids. But it makes perfect sense to a Deaf audience. A Deaf character who doesn't wear hearing aids is rejecting hearing society and making a statement about hearing culture or Deaf Culture that a hearing reader might not understand. Mainstream society is more than willing to suspend disbelief for the narrative of ghosts and dragons, of aliens and new languages, but the hardened truth of ableism or racism seems to be disbelieved in every imagined context.
Selective imagination is killing us. When we can imagine ourselves in the future, when we can imagine ourselves in public, when we can imagine ourselves everywhere in society, we have the ability to live. When our opportunities are cut off, our choices curtailed, our imagined futures denied…that kills us figuratively, but forcing disabled people to stop imagining possible hopeful futures causes harm that can result in severe depression and suicidality.
Constraining imagination has consequences.
I'm trying to show my partner's 5-year-old in small conversations about how her imagination has power, the power to shape her world for good or ill. When she tells me that I can't do something because I'm blind, I ask her where she learned it. That she is imagining the truth of someone else's body—and that can cause harm.
The stories we tell ourselves about other people come from our imaginations, too.
These conversations, these meditations on story with a 5-year-old driving the bus remind me that the imagination is more powerful than we think.
© 2021 Elsa Sjunneson
Elsa Sjunneson
Award winning editor Elsa Sjunneson is a Deafblind hurricane in a vintage dress. She writes fiction, non-fiction and game design materials which can be found in many exciting places. She lives in Seattle, WA, and fights structural ableism in her free time. Her debut memoir, Being Seen: One Deafblind Woman's Fight To End Ableism, releases in 2021 from Simon & Schuster.


A family practitioner who was a longtime associate dean for student affairs at the Medical College of Georgia at Augusta University and a radiation oncologist who is executive director of the Winship Cancer Institute at Emory University are recipients of the 2017 MCG Distinguished Alumni awards.
Dr. Mason Thompson, a 1973 graduate of the state's public medical school and the newest president of the MCG Alumni Association, is the recipient of the Distinguished Alumnus Award for Loyalty. He returned to his alma mater in 1978 as an assistant, and eventually, associate professor of family medicine. He was appointed MCG's assistant dean for student affairs in 1992 and served as the associate dean for student affairs from 1993-2000. He has also been the interim associate dean for minority affairs, chair of the MCG Admissions Committee and associate dean for admissions. He has been an active member of the MCG Foundation's Board of Directors since 2006 and associate professor emeritus since 2007.
Thompson was a member of the Section on Medical Schools for the American Medical Association and the Group on Student Affairs for the Association of American Medical Colleges from 1992-2007. He was a member of the National Advisory Committee to the AAMC's American Medical College Application Service from 2004-06.
His research has focused on the progression and development of family medicine practice, particularly in the areas of smoking cessation, non-familial hypercholesterolemia and anxiety.
Dr. Walter Curran, a 1982 graduate, is MCG's Distinguished Alumnus for Professional Achievement. Curran has served as executive director at Winship, one of the nation's top-ranked cancer centers, since 2009. He also is Georgia Research Alliance Eminent Scholar and Chair in Cancer Research there, Lawrence W. Davis Professor and chairman of the Department of Radiation Oncology for the Emory University School of Medicine, and associate vice president for cancer for Emory's Woodruff Health Sciences Center.
A national leader, he is co-chairman of the American Joint Commission on Cancer, founding chairman of the NRG Oncology Foundation, and founding chairman of the board for the RTOG Foundation, the successor to the National Cancer Institute-funded Radiation Therapy Oncology Group. He also serves on committees such as the Coalition of National Cancer and Cooperative Groups, American Cancer Society and the National Cancer Institute.
Curran's research revolves around the safe and effective use of radiation oncology to treat all types of cancer. His influence and passion have resulted in over 240 selected lectureships, seminar invitations and visiting professorships, including serving as keynote speaker for the International Lung Cancer Congress in 2012.


text:
Mario is Missing!
Super Nintendo Game (SNES)
Mario has gone missing! Follow Luigi and find all the clues that will lead you to Mario in this fun educational video game - Mario is Missing!
Mario is Missing! is a classic educational video game released back in 1993 and is available on various gaming consoles including the Super Nintendo Entertainment System (SNES). While it has some point and click elements, the console version of the game focuses on platforming. In this game, Bowser has relocated the entire Mushroom Kingdom into the real world! Find a way to solve the problem and find Mario!
A = X S = Y
D = L C = R
Crash Bandicoot - The Huge Adventure
Wario Land 4
Crash Bandicoot - The Huge Adventure Super Mario Advance 4 Wario Land 4 Pokemon Emerald Version Super Mario World
Mario is Missing! is an online SNES game that you can play at Emulator Online. This free Super Nintendo game is the United States of America region version for the USA. Mario is Missing! is a single title from the many trivia games, platform games and mario games offered for this console. If you enjoyed playing this, then you can find similar games in the snes games category. Mario is Missing! game is from the various retro games on the site, and there are more games like this, including Super Mario 64, Classic Tetris and Mario is Missing! Done Right.


Ultrasound is a type of mechanical energy that has been used for many years to treat chronic pain and improve the healing process. There are several specific ways a physical therapist can use ultrasound therapy to treat injuries and reduce pain. Contact Appalachian Physical Therapy to learn more about how ultrasound therapy can help you promote healing, reduce pain, and improve your ability to perform daily activities and tasks.
Promote Tissue Healing – Ultrasound not only improves your muscles and joint range of motion, but can aid in the healing of wounded tissues. The metabolism of the cells in the tissue is affected by ultrasound. The vibration produced by the ultrasound can help prevent scar tissue from forming.
The goal of the physical therapist is to alleviate your symptoms and promote healing. This will ultimately improve flexibility and range of motion. It will also help reduce or eliminate any pain associated with your injury or ailment. A physical therapist can also teach you exercise strategies that you can do on your own and ways you can improve your posture and gait to avoid future injury. The goal of the physical therapist is to ultimately help you improve strength, the range of motion, and daily functionality. Contact Us Today at Pinehurst, NC & Harrisonburg & Broadway, VA Centers for more information regarding how ultrasound therapy can treat your condition.
For more information on Imaging in Healthcare, click here for our brochure.