text:
The most widely read and highly cited peer-reviewed neurology journal
May 22, 2007; 68 (21) Articles
Naproxen and celecoxib do not prevent AD in early results from a randomized controlled trial
ADAPT Research Group
First published April 25, 2007, DOI: https://doi.org/10.1212/01.wnl.0000260269.93245.d2
Neurology May 2007, 68 (21) 1800-1808; DOI: 10.1212/01.wnl.0000260269.93245.d2
Info & Disclosures
Objective: To evaluate the efficacy and safety of naproxen and celecoxib for the primary prevention of Alzheimer disease (AD).
Methods: Randomized, placebo-controlled, double-masked clinical trial conducted at six US dementia research clinics. Volunteers aged 70+ years, with cognitive screening scores above designated cut-offs and a family history of AD, were randomly assigned to celecoxib 200 mg BID, naproxen sodium 220 mg BID, or placebo. Enrollment began in early 2001. The main outcome measure was diagnosis of AD after randomization.
Results: On December 17, 2004, treatments were suspended. Events while on treatment yielded hazard ratios vs placebo of 1.99 (95% CI 0.80 to 4.97; p = 0.14) for celecoxib and 2.35 (0.95 to 5.77; p = 0.06) for naproxen. Imperfect screening measures led to enrollment of 7 individuals with dementia and 46 others with milder cognitive syndromes. Their (prevalent) illness was detected at enrollment and diagnosed within 6 months following randomization. Secondary analyses that excluded the 7 cases of prevalent dementia showed increased hazard ratios for AD with both treatments. Neither treatment produced a notable effect on the incidence of milder cognitive syndromes.
Conclusions: These results do not support the hypothesis that celecoxib or naproxen prevent Alzheimer dementia, at least within the early years after initiation of treatment. Masked long-term follow-up of these participants will be essential.
While the causes of Alzheimer disease (AD) are not well understood,1,2 neuropathologic evidence indicates that inflammatory processes are involved.3 Inflammatory mechanisms are also suggested by epidemiologic findings that users of nonsteroidal anti-inflammatory drugs (NSAIDs) show reduced incidence of Alzheimer dementia.4 A recent meta-analysis yielded a hazard ratio (HR) for incident AD of 0.42 (95% CI 0.26 to 0.66) among individuals with 2 or more years of sustained NSAID exposure, compared with nonusers.5
Interest in NSAIDs as a treatment for AD was initially reinforced by a promising randomized controlled trial.6 However, several subsequent trials have shown no benefit from treatment of AD with rofecoxib,7,8 naproxen,8 nimesulide,9 or diclofenac.10 A trial of rofecoxib to prevent progression to AD in those with mild cognitive impairment (often a prodromal phase of AD) was similarly disappointing.11 However, trials have not tested the hypothesis, suggested by epidemiologic data, that NSAIDs may be useful for the primary prevention of AD, i.e., for reducing its incidence in individuals with normal cognition. The AD Anti-inflammatory Prevention Trial (ADAPT) was designed to investigate whether the selective cyclooxygenase-2 (COX-2) inhibitor celecoxib (Celebrex, Pfizer) or the dual-inhibitor NSAID naproxen sodium (Aleve, Bayer) could prevent AD or delay cognitive decline. We report ADAPT results on occurrence of AD by treatment group, with secondary outcomes of the incidence of all-cause dementia and AD prodromes including amnestic mild cognitive impairment (aMCI). ADAPT results with regard to safety of the treatments are reported elsewhere.12
Design overview.
ADAPT is a randomized, placebo-controlled, multicenter, primary prevention trial. Specifics regarding study design and eligibility criteria are available elsewhere.13,14 Registered on ClinicalTrials.gov (#NCT00007189), ADAPT is investigator-initiated and sponsored by the National Institute on Aging (NIA) via a cooperative agreement. Recruitment was accomplished primarily through mailings to Medicare beneficiaries targeted by age and by zip code to areas surrounding the trial's six field sites (Baltimore, MD; Boston, MA; Rochester, NY; Seattle, WA; Sun City, AZ; and Tampa, FL). Eligible participants (see below) were aged ≥70 years and had a history of at least one first-degree relative with Alzheimer-like dementia. Persons regularly using NSAIDs were excluded, but regular aspirin use was allowed in dosage ≤81 mg per day. All pertinent institutional review boards (IRBs) approved the study protocol. Consent for participation was obtained from each person and a collateral informant. Enrollment began in March 2001.
Participants were randomly assigned to receive celecoxib (200 mg twice daily), naproxen sodium (220 mg twice daily), or matching placebos. The randomization scheme used permuted blocks with assignment ratio 1:1:1.5. Randomization was stratified by three age groups (ages 70 to 74, ages 75 to 79, and ages 80+) and by the six field sites, using a distributed computerized system that released treatment assignment only after baseline data were keyed and eligibility confirmed.
The study's Treatment Effects Monitoring Committee (TEMC) met twice yearly to review efficacy and safety data by treatment assignment. The Committee comprised five members external to ADAPT (voting), and three representatives of the ADAPT Steering Committee (non-voting).
Procedures.
Study staff reviewed the eligibility of prospective participants using specified health criteria and cut-off scores on an Eligibility Battery of cognitive tests, which included the Modified Mini-Mental State Examination (3MS-E),15 the Hopkins Verbal Learning Test-Revised (HVLT-R),16 and the informant-based Dementia Severity Rating Scale (DSRS).17 Eligible individuals returned for an enrollment visit at which time their baseline cognitive and functional abilities were assessed using a more elaborate Cognitive Assessment Battery (CAB) that included the 3MS-E, Digit Span Test, Generative Verbal Fluency (name as many supermarket items as possible in 1 minute), narratives from the Rivermead Behavioral Memory Test,18 HVLT-R, Brief Visuospatial Test-Revised,19 self-rating of memory functions, 20 Geriatric Depression Scale,21 and the informant-rated DSRS. This same battery (with equivalent alternate test forms for some items) was used each year thereafter in follow-up screening for incident cognitive syndromes.
Participants and collateral informants were interviewed at 1 month and 6 months after randomization and annually thereafter. Telephone interviews were conducted with participants and informants approximately every 6 months between visits, starting at month 3. Interviews focused on health history and treatment compliance, but also collected information about change in cognitive or functional abilities.
Outcome assessment.
Suspected cognitive syndromes were identified using a sensitive cut-off procedure on annual CAB assessments (including baseline measures) or, occasionally, upon referral from study clinicians. Participants with a suspected cognitive syndrome were invited to return for a dementia evaluation (DE). Expert physicians, trained study nurses, and psychometrists conducted the DEs following a protocol that included a detailed history from participants and informants, physical, neurologic, and mental status examinations, and a detailed psychometric assessment battery. The latter again included the informant-rated DSRS, and also the Dementia Questionnaire–clinical revision22; the Neuropsychiatric Inventory23; the CERAD cognitive test battery24; Trail Making Test25; Logical Memory26; Benton Visual Retention Test27; Controlled Oral Word Association Test28; Symbol Digit Modalities Test29; Shipley Vocabulary30; and Self-rating of Memory Functions.20 Where appropriate, participants with a cognitive syndrome were referred for laboratory testing and neuroimaging for differential diagnosis.
All resulting DE, laboratory, and neuroimaging data were then reviewed by a diagnostic panel of experts including the examining clinicians, other ADAPT physicians, and senior site neuropsychologists. Where appropriate, participants with abnormal cognition received diagnoses of dementia using the Diagnostic and Statistical Manual of Mental Disorders–IV criteria,31 or Alzheimer's dementia using the National Institute of Neurological and Communicative Disorders and Stroke–Alzheimer's Disease and Related Disorders Association criteria.32 Among the remaining cognitively impaired individuals, we identified instances of aMCI13 or, in some participants who did not meet the specific criteria for MCI, other mild cognitive disorders suggestive of prodromal AD (prAD), as used in the Cache County study.33 To promote diagnostic consistency across the field sites, several cases from each site were reviewed at semi-annual meetings of the ADAPT clinical personnel.
By convention, the date of onset of any cognitive syndrome was taken as the date of the relevant DE visit. Notably, seven CABs administered at enrollment triggered DEs, conducted over the following 6 months, that resulted in a diagnosis of dementia. Another 46 enrollment CABs resulted in DEs that identified diagnoses of aMCI or prAD.34
Treatment discontinuation.
On December 17, 2004, the National Cancer Institute–sponsored Adenoma Prevention with Celecoxib (APC) trial announced significantly increased cardiovascular risk with celecoxib. On the same day, the ADAPT Steering Committee suspended treatment with celecoxib and naproxen, and suspended enrollment. On March 31, 2005, the Steering Committee made these suspensions permanent.35
Data analysis.
Because we performed cognitive screening only once a year, and treatment termination took place in the middle of an annual cycle of follow-up assessments, we analyzed outcomes ascertained at DEs that were triggered by CABs conducted on or before June 17, 2005, 6 months after termination of treatments. To contribute an "event," DEs must then have been completed within 3 months of this date and outcomes entered into the ADAPT database by December 17, 2005. Outcome analyses included only participants with at least one cognitive assessment after enrollment. Person-time was censored after participants' last completed cognitive assessment. By design, active treatments were compared individually with placebo and not with each another. In all instances, we used the principle of intention-to-treat (ITT) when comparing the occurrence of diagnostic outcomes by assigned treatment. In addition to the primary analyses of AD identified following randomization, we conducted analyses (specified a priori) of the incidence of AD or all-cause dementia after exclusion of seven participants who had passed the screening eligibility battery but had dementia (diagnosed later) that had been detected at their enrollment visit. In other analyses we estimated post hoc the incidence of aMCI or suspected prAD after exclusion of all individuals with cognitive impairment identified at enrollment and diagnosed within the subsequent 6 months.
We evaluated time-to-occurrence of each outcome using Kaplan-Meier plots, with p values of associated log-rank χ2 tests. Cox proportional hazards regression models permitted adjustment for the stratification variables of age group and field site and semi-parametric estimation of the relative treatment effects. Resulting adjusted HRs were estimated with 95% CIs and Wald p values. These analyses used the PHREG routine in SAS, version 8.
Study population.
As of December 17, 2004, ADAPT had recruited 2,528 participants. Figure 1 shows the flow of these participants from randomization forward. Some 403 participants did not contribute to the analyses for one of three reasons: 1) their observations were censored before their first annual follow-up (179); 2) they did not return for cognitive follow-up (210); or 3) no information on cognition was available because they had refused or not completed a requested Dementia Evaluation.14 These losses were distributed proportionally across treatment groups (Fisher exact p = 0.54). The seven participants with dementia at enrollment and the 46 with other cognitive syndromes identified at enrollment were also distributed proportionally by treatment group (p = 0.23 and 0.89). There were 51 deaths: 17 in those receiving celecoxib (2.3%); 16 in the naproxen-treated group (2.2%); and 18 in those on placebo (1.7%) (p = 0.38 for naproxen vs placebo, and 0.30 for celecoxib). Median follow-up times following treatment assignment were 733 days for celecoxib-, 734 days for naproxen-, and 734.5 days for placebo-assigned participants. Participants reported that they actually took celecoxib for a median 561 days (25th percentile = 358, 75th percentile = 829), with corresponding figures of 546 days (350, 813) for naproxen, and 559 days (353, 848.5) for placebo (exact p = 0.31). While taking the study treatments, 85.6% of participants on celecoxib reported taking drug always or almost always or most of the time, compared with 86.1% on naproxen and 87.9% on placebo. Among participants assigned to celecoxib, 10.7% reported taking proscribed doses of aspirin or NSAID medications at least once, compared with 9.9% of participants on naproxen and 13.3% on placebo.
Figure 1 Participant flow (CONSORT) chart
*Numbers available only for those randomized, not those screened for eligibility. †Participants considered to have terminated study drug if study drug had been started but was no longer being issued prior to December 17, 2004; does not include temporary interruptions. ‡Participants considered administratively censored if their 1-year visit window had not closed by June 17, 2005. §Participants considered lost to cognitive assessment after 1 or more years if they did not have cognitive assessment data in the 1.5 years before June 17, 2005; losses include deaths.
Table 1 provides baseline and demographic characteristics by treatment group for the 2,528 randomized participants and for the 2,128 who contributed to the analyses of cognitive outcomes. More men than women were enrolled. Race/ethnicity was predominantly white. Over three-quarters of the population had more than a high school education, and most had a Karnofsky score of 100. Baseline characteristics, including rates of cardiovascular diseases, were similar for the three treatment groups.
Table 1 Study population at entry: all participants randomized and participants who contributed to the analyses of cognitive outcome
Diagnostic rates by treatment assignment.
Table 2 displays counts, rates, and 95% CIs of diagnostic events per person year of follow-up by treatment group. In addition to occurrence of AD following randomization, the table displays rates of AD and all-cause dementia after exclusion of the seven participants with dementia detected at enrollment. Also shown are crude rates for incidence of MCI or prAD in a secondary analysis that excluded the 53 participants with any cognitive impairment syndrome at enrollment. Neither treatment was associated with reduction in the incidence of AD, all cause-dementia, or the AD prodromes. Instead, there was a suggestion of increase in the incidence of AD with both treatments.
Table 2 Rates of cognitive outcomes by treatment group
Time-to-event analyses.
The primary analyses of time to onset of AD are shown in the Kaplan-Meier plot of figure 2. The associated log-rank tests compare each treatment with placebo. A similar time-to-onset analysis that excluded the seven prevalent cases of dementia (not shown) produced log rank χ2p values of 0.02 for celecoxib vs placebo and 0.04 for naproxen vs placebo. These results do not suggest a reduction in the occurrence of AD with either NSAID but, if anything, the reverse. Figure 3 shows little difference across treatments in time-to-event analyses of incident MCI or prAD.
Figure 2 Time-to-event plot for Alzheimer dementia following randomization
Time-to-event plot for Alzheimer dementia following randomization, comparing placebo-, celecoxib-, and naproxen-treated groups, with p values from the log-rank χ2 tests comparing each treatment with placebo.
Figure 3 Time-to-event plot for secondary analyses of Alzheimer-like prodromes
Time-to-event plot for secondary analyses of Alzheimer-like prodromes, comparing placebo-, celecoxib-, and naproxen-treated groups, with p values from log-rank χ2 tests comparing each treatment to placebo. Individuals with any cognitive impairment syndrome detected at enrollment were excluded.
Table 3 shows results from corresponding proportional hazards models. In the primary analyses of all events following randomization, the hazard for AD was approximately doubled with either celecoxib or naproxen, but the related CIs included the null value of 1. Analyses that excluded the seven cases of prevalent AD yielded HRs further from the null, with significant p values. The HR for the composite of MCI and prodromal AD did not differ much from unity.
Table 3 Hazard ratios (HRs) for cognitive outcomes
Table 4 displays results from proportional hazards models estimating the risk of AD or death (composite outcome, death being an obvious censoring variable). The results do not change the conclusion from table 3 of no benefit with the study treatments.
Table 4 Hazard ratios (HRs) for risk of death or Alzheimer disease (composite)
Although ADAPT was conducted to test the hypothesis that celecoxib or naproxen reduce the incidence of AD, these results indicate no such effect, at least over the study's period of observation. Based on these findings, the lower bounds of the HR CIs in the primary analyses, 0.80 for celecoxib and 0.95 for naproxen, imply with 95% confidence that the treatments conferred no more than 20% (celecoxib) or 5% (naproxen) reduction in risk of AD. Using similar reasoning, the treatments provided no more than 24% or 28% protection against aMCI or prAD.
The primary analyses that included all events following randomization showed an inconclusive trend toward increased AD incidence with either NSAID treatment. Owing to the imperfect sensitivity of our screening protocol, these events included seven cases of AD whose dementia, although diagnosed later, was present at the time of randomization. While it makes little sense clinically to include these individuals with prevalent AD in the at-risk pool, their inclusion in the primary analyses is warranted by a fundamental objective of clinical trials: freedom from bias. Nevertheless, we recognized that the inclusion of these seven individuals could potentially dilute any treatment effects. This concern, magnified here by the small number of events, led to a decision a priori to conduct additional analyses that excluded these individuals. As predicted, these latter analyses yielded HRs that were more extreme (table 3). Despite the reduction in number of events from 32 (a small number) to 25 (a smaller number), the corresponding p values also met conventional criteria for statistical significance, even though a power analysis with 25 events would have suggested that only a very extreme HR could be reliably detected as "significant."
It is probably noteworthy that the effects of the two treatments seem broadly interchangeable. This fact would seem to reduce the probability that the observed HRs are attributable purely to chance. Furthermore, the findings trend in the same direction as the results of a recent trial of the selective COX-2 inhibitor rofecoxib in patients with MCI,11 and also the results of a widely cited trial of naproxen and rofecoxib for treatment of Alzheimer dementia8 that showed trends toward negative effects of rofecoxib.
These findings from a randomized controlled trial therefore appear to be inconsistent with epidemiologic findings suggesting reduced AD incidence following sustained NSAID use.4 A common explanation for such divergent results posits that the inverse association in the observational work reflects the effects of unknown variables confounded with NSAID use. Another explanation might be that the ADAPT findings relate specifically to celecoxib or naproxen but not to other NSAIDs such as ibuprofen, a common exposure in observational studies, because the ADAPT treatments do not lower production of amyloidogenic Aβ 42,36 a probable early step in the development of AD pathology.
A more speculative explanation that may tie together the epidemiologic and clinical trials findings posits that the effects of NSAID exposures differ with the stage of brain disease progression. NSAIDs suppress brain inflammatory mechanisms, particularly the secretion by activated microglia of proinflammatory cytokines that are widely thought to promote AD pathogenesis. Especially given the extended presymptomatic period of AD neurodegeneration,2 it is therefore possible that NSAID suppression of microglial activation might exert protective effects when given years before the development of symptoms. Once extensive Aβ deposits have occurred, however, microglia-mediated inflammatory mechanisms may be essential to their clearance. At this later stage, when symptoms may be imminent or evident, NSAID suppression of microglial activity could have mixed effects or even accelerate the disease process, thus precipitating the onset of dementia.
This last explanation is consistent with data from both the Rotterdam and Cache County observational studies.5,37 Both studies suggest no protection with NSAIDs used in the last 2 years before dementia onset. If timing of exposure determines whether NSAIDs produce benefit or harm, the ADAPT results should logically be compared with observational study subjects having only recent NSAID exposure, i.e., those for whom the observational studies do not suggest protection. In this way, the emerging evidence base on AD protection with NSAIDs may simulate the findings with hormone replacement therapy (HRT) in women. HRT observational studies suggest that hormones may prevent AD if given years before the typical age at onset,38–40 but may increase risks when used later in life.20,41 Like the women who developed incident dementia in the Women's Health Initiative Memory Study40 (WHIMS), the incident AD cases in ADAPT developed their symptoms within a few years of exposure to the intervention. In both trials, those who developed dementia within a short span of time were likely to have had advanced pre-clinical Alzheimer brain changes when the intervention was administered.
Because the observational data suggest that NSAIDs may have protective effects for individuals with "healthier" brains (i.e., for those whose onset of AD would be some years in the future), continued observations in the ADAPT cohort could show mitigation—or even reversal—of the treatment effects that presently appear null or negative. This idea should be tested directly through continued masked follow-up of the ADAPT cohort. For now, we suggest that the ADAPT treatments are not indicated for the prevention of AD. By contrast, our findings are too limited to be considered evidence that persons at risk for AD should avoid these or other NSAIDs when used for their approved indications.
The writing group is indebted to Amanda Blackford for carrying out the statistical analyses reported in this article.
ADAPT Steering Committee: Chair—Curtis Meinert, PhD, Johns Hopkins Bloomberg School of Public Health, Baltimore (through February 2005), Denis Evans, MD, Rush-Presbyterian-St. Luke's Medical Center, Chicago (since March 2005); Resource center representatives/Study officers (voting)—John Breitner, MD, MPH (Study Chair), Veteran Affairs Puget Sound Health Care System and University of Washington School of Medicine, Seattle, Neil Buckholtz, PhD (Project Officer), National Institute on Aging, Bethesda, Barbara Martin, PhD (Coordinating Center Deputy Director), Johns Hopkins Bloomberg School of Public Health, Baltimore, Curtis Meinert, PhD (Coordinating Center Director), Johns Hopkins Bloomberg School of Public Health, Baltimore, Susan Molchan, MD (Project Officer), National Institute on Aging, Bethesda; Field site directors (voting)—Suzanne Craft, PhD, Veteran Affairs Puget Sound Health Care System and University of Washington School of Medicine, Seattle, Robert C. Green, MD, MPH, Boston University School of Medicine, Boston, Constantine Lyketsos, MD, MHS, Johns Hopkins School of Medicine, Baltimore, Michael Mullan, MD, PhD, The Roskamp Institute Memory Clinic, Tampa, Marwan Sabbagh, MD, Sun Health Research Institute, Sun City, AZ, Pierre Tariot, MD, Banner Health System, Phoenix AZ (through October 2005), M. Saleem Ismail, MD, University of Rochester School of Medicine, Rochester, NY (since December 2005); Other voting members—Jason Brandt, PhD, Johns Hopkins School of Medicine, Baltimore, Steven Piantadosi, MD, PhD, Johns Hopkins School of Medicine, Baltimore; Staff—Janette Negele and Melissa Montero, Veteran Affairs Puget Sound Health Care System, Seattle, Bonnie Piantadosi, MSW, MPH, Johns Hopkins Bloomberg School of Public Health, Baltimore; Consultants—Themistocles Dassopoulos, MD, Johns Hopkins School of Medicine, Baltimore, Claudia Kawas, MD, University of California Irvine, Leon Thal, MD, University of California San Diego, La Jolla, Kathleen Welsh-Bohmer, PhD, Duke University Medical Center, Durham, Andrew Whelton, MD, Hunt Valley, MD.
Treatment Effects Monitoring Committee: Voting members—C. Morton Hawkins, PhD (Chair), Frontier Science & Technology Research Foundation, Madison, Bernard Carroll, MBBS, PhD, FRCPsych, Pacific Behavioral Research Foundation, Carmel, CA, Ronald Petersen, PhD, MD, Mayo Clinic, Rochester, MN, Thomas Schnitzer, MD, PhD, Northwestern University, Chicago, Dallas High, PhD, retired (through June 2004); Non-voting members—Neil Buckholtz, PhD, National Institute on Aging, Bethesda, Denis Evans, MD, Rush-Presbyterian-St. Luke's Medical Center, Chicago, Curtis Meinert, PhD, Johns Hopkins Bloomberg School of Public Health, Baltimore.
Other members of Research Group: Resource centers—Chairman's Office, Veteran Affairs Puget Sound Health Care System, Seattle: John Breitner, MD, Director; Janette Negele, Coordinator; Melissa Montero, Coordinator; Elizabeth Aigbe, MS; Jill Dorje; Brenna Cholerton, PhD; Coordinating Center, Johns Hopkins Bloomberg School of Public Health, Baltimore: Curtis Meinert, PhD, Director; Barbara Martin, PhD, Associate Director; Bonnie Piantadosi, MSW, MPH, Coordinator; Robert Casper, MS; Michele Donithan, MHS; Hsu-Tai Liu, MD, MPH; Anne V. Shanklin, MA, CCRP; Project Office, National Institute on Aging, Bethesda: Neil Buckholtz, PhD, Project Officer; Susan Molchan, MD, Project Officer; Field sites—Johns Hopkins School of Medicine, Baltimore: Constantine Lyketsos, MD, Director; Martin Steinberg, MD, Associate Director; Jason Brandt, PhD, Neuropsychologist; Julia J. Pedroso, RN, MA, Coordinator; Alyssa Bergey; Themos Dassopoulos, MD; Melanie Dieter, MA; Carol Gogel, RN; Chiadi Onyike, MD; Lynn Smith; Veronica Wilson-Sturdivant; Nadine Yoritomo, RN; Boston University School of Medicine, Boston: Robert Green, MD, Director; Sanford Auerbach, MD, Associate Director; Robert Stern, PhD, Neuropsychologist; Mary-Tara Roth, RN, MSN, MPH, Coordinator; Lorraine Baldwin; Margaret Brickley, MS, RN, NP; Patrick Compton, RN; Debra Hanna, RN, BC, MPH; Sylvia Lambrechts; Jane Mwicigi, MD, MPH; Mayuri Thakuria, MD, MPH; University of Rochester School of Medicine, Rochester: Saleem Ismael, MD, Director; Pierre Tariot, MD, Director (through October 2005); J. Michael Ryan, MD, Associate Director; Robin Henderson-Logan, PhD, ABPP-CN, Neuropsychologist; Colleen McCallum, MSW, Coordinator; Laura Jakimovick, RN, MS; Kara Jones, RN; Arlene Pustalka, RN; Asa Widman; Helen Decker, RPA; Veteran Affairs Puget Sound Health Care System and University of Washington School of Medicine, Seattle: Suzanne Craft, PhD, Director; Mark Fishel, MD, Associate Director; Laura Baker, PhD, Neuropsychologist; Kathleen Nelson, RN, Coordinator; Susan Bigda, RN; Yoshie Biro; Ruth Boucher, RN; Deborah Dahl, RN; Nickolas Dasher; Edward DeVita, MD; Grace Garrett; Austin Hamm; Jeff Lindsey; Laura Sissons-Ross; Sun Health Research Institute, Sun City, AZ: Marwan Sabbah, MD, Director; Joseph Rogers, PhD, Associate Director; Donald Connor, PhD, PhD, Neuropsychologist; Carolyn Liebsack, RN, BSN, CCRC, Coordinator; Joanne Ciemo, MD; Kathryn Davis; Theresa Hicksenhiser, LPN; Sherry Johnson-Traver; Healther Kolody; Lisa Royer, RN; Nina Silverberg, PhD; Deborah Tweedy, RN, MSN, CNP; The Roskamp Institute Memory Clinic, Tampa: Michael Mullan, MD, PhD; Timothy Crowell, PsyD, Associate Director, Neuropsychologist; Julia Parrish, LPN, Coordinator; Theavy Chea; Scott Creamer; Melody Brooks Jayne, MD; Antoinette Oliver, MA; Summer Price, MA; Joseph Zolton, ERT.
Received September 18, 2006. Accepted in final form January 21, 2007.
Ferri CP, Prince M, Brayne C, et al. Alzheimer's Disease International. Global prevalence of dementia: a Delphi consensus study. Lancet 2005;366:2112–2117.
Rabins PV, Lyketsos CG, Steele CD. Practical dementia care, 2nd ed. Oxford University Press; 2006.
Rosenberg P. Clinical aspects of inflammation in Alzheimer's disease. Int Rev Psychiatry 2005;17:503–514.
McGeer PL, Schulzer M, McGeer EG. Arthritis and anti-inflammatory agents as possible protective factors for Alzheimer's disease: a review of 17 epidemiologic studies. Neurology 1996;47:425–432.
Szekely CA, Thorne JE, Zandi PP, et al. Nonsteroidal anti-inflammatory drugs for the prevention of Alzheimer's disease: a systematic review. Neuroepidemiology 2004;23:159–169.
Rogers J, Kirby LC, Hempelman SR, et al. Clinical trial of indomethacin in Alzheimer's disease. Neurology 1993;43:1609–1611.
Reines SA, Block GA, Morris JC, et al. Rofecoxib Protocol 091 Study Group. Rofecoxib: no effect on Alzheimer's disease in a 1-year, randomized, blinded, controlled study. Neurology 2004;62:66–71.
Aisen PS, Schafer KA, Grundman M, et al. Alzheimer's Disease Cooperative Study. Effects of rofecoxib or naproxen vs placebo on Alzheimer's disease progression: a randomized controlled trial. JAMA 2003;289:2819–2826.
Aisen PS, Schmeidler J, Pasinetti GM. Randomized pilot study of nimesulide treatment in Alzheimer's disease. Neurology 2002;58:1050–1054.
Scharf S, Mander A, Ugoni A, et al. A double-blind, placebo-controlled trial of diclofenac/misoprostol in Alzheimer's disease. Neurology 1999;53:197–201.
Thal LJ, Ferris SH, Kirby L, et al. Rofecoxib Protocol 078 Study Group. A randomized, double-blind, study of rofecoxib in patients with mild cognitive impairment. Neuropsychopharmacology 2005;30:1204–1215.
ADAPT Research Group. Cardiovascular and cerebrovascular events in the randomized, controlled Alzheimer's Disease Anti-inflammatory Prevention Trial (ADAPT). PLoS Clin Trials. November 2006; 1(7): e33. doi: 10.1371/journal.pctr.0010033.
ADAPT protocol, version 1.4, dated November 19, 2002. Available at: http://www.jhucct.com/adapt/manall43.pdf. Accessed December 10, 2006.
Martin BK, Meinert CL, Breitner JC, ADAPT Research Group. Double placebo design in a prevention trial for Alzheimer's disease. Control Clin Trials 2002;23:93–99.
Teng EL, Chui HC. The Modified Mini-Mental State (3MS) examination. J Clin Psychiatry 1987;48:314–318.
Brandt J. The Hopkins Verbal Learning Test: development of a new verbal memory test with six equivalent forms. Clin Neuropsychol 1991;5:125–142.
Clark CM, Ewbank DC. Performance of the Dementia Severity Rating Scale: a caregiver questionnaire for rating severity in Alzheimer's disease. Alzheimer Dis Assoc Disord 1996;10:31–39.
Wilson B, Cockburn J, Baddeley A, Hiorns R. The development and validation of a test battery for detecting and monitoring everyday memory problems. J Clin Exp Neuropsychol 1989;11:855–870.
Benedict RH, Schretlen D, Groninger L, Dobrashki M, Shpritz B. Revision of the Brief Visuospatial Memory tests: studies of normal performance, reliability and validity. Psychol Assess 1996;8:145–153.
Squire LR, Wetzel CD, Slater PC. Memory complaint after electroconvulsive therapy: assessment with a new self-rating instrument. Biol Psychiatry 1979;14:791–801.
Yesavage JA, Brink TL, Rose TL, Leirer VO. Development and validation of a geriatric depression screening scale: a preliminary report. J Psychiatry Res 1983;17:37–49.
Silverman JM, Breitner JCS, Mohs RC, Davis KL. Reliability of the family history method in genetic studies of Alzheimer's disease and related dementias. Am J Psychiatry 1986;143:1279–1282.
Cummings JL, Mega M, Gray K, et al. The Neuropsychiatric Inventory: comprehensive assessment of psychopathology in dementia. Neurology 1994;44:2308–2314.
Morris JC, Heyman A, Mohs RC, et al. The Consortium to Establish a Registry for Alzheimer's Disease (CERAD). Part I. Clinical and neuropsychological assessment of Alzheimer's disease. Neurology 1989;39:1159–1165.
Reitan RM. Trail Making Test: Manual for Administration and Scoring. Tucson: Reitan Neuropsychological Laboratory, 1986.
Wechsler D. Wechsler Memory Scale–Revised Manual. San Antonio: Psychological Corporation; 1987.
Benton A. Revised Visual Retention Test, 4th ed. New York: Psychological Corporation; 1974.
Benton A, Hamsher K. Multilingual Aphasia Examination. Iowa City: University of Iowa Press; 1988.
Smith A. Symbol Digit Modalities Test—manual. Los Angeles: Western Psychological Services; 1982.
Zachary RA. Shipley Institute of Living Scale—Revised manual. Los Angeles: Western Psychological Services; 1991.
American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders, 4th ed. Washington, DC: American Psychiatric Association; 1994.
McKhann G, Drachman D, Folstein M, et al. Clinical diagnosis of Alzheimer's disease: report of the NINCDS-ADRDA Work Group under the auspices of the Department of Health and Human Services Task force on Alzheimer's disease. Neurology 1984;34:939–944.
Tschanz JT, Welsh-Bohmer KA, Lyketsos CG,et al. for the Cache County Investigators. Conversion to dementia from mild cognitive disorder: the Cache County Study. Neurology 2006;67:229–234.
Graham JE, Rockwood K, Beattie BL. Prevalence and severity of cognitive impairment with and without dementia in an elderly population. Lancet 1997;349:1793–1796.
Statement from the Steering Committee of the Alzheimer's Disease Anti-inflammatory Prevention Trial (ADAPT) for communication to the FDA Arthritis Advisory Committee and the Drug Safety and Risk Management Advisory Committee, 18 February 2005. Available at: http://www.jhucct.com/adapt/pdf%20documents/FDA%20ADAPT%20STATEMENT_web%20posting.pdf. Accessed December 10, 2006.
Weggen S, Eriksen JL, Das P, et al. A subset of NSAIDs lower amyloidogenic Abeta42 independently of cyclooxygenase activity. Nature 2001;414:212–216.
in t'Veld BA, Ruitenberg A, Hofman A, et al. Nonsteroidal antiinflammatory drugs and the risk of Alzheimer's disease. N Engl J Med 2001;345:1515–1521.
Kawas C, Resnick S, Morrison A, et al. A prospective study of estrogen replacement therapy and the risk of developing Alzheimer's disease: the Baltimore Longitudinal Study of Aging. Neurology 1997;48:1517–1521.
Zandi PP, Carlson MC, Plassman BL, et al. Cache County Memory Study Investigators. Hormone replacement therapy and incidence of Alzheimer's disease in older women: the Cache County Study. JAMA 2002;288:2123–2129.
Breitner JC, Zandi PP. Effects of estrogen plus progestin on risk of dementia. JAMA 2003;290:1706–1707.
Shumaker SA, Legault C, Kuller L, et al. Women's Health Initiative Memory Study. Conjugated equine estrogens and incidence of probable dementia and mild cognitive impairment in postmenopausal women: Women's Health Initiative Memory Study JAMA 2004;291:2947–2958.
Disputes & Debates: Rapid online correspondence
NOTE: All authors' disclosures must be entered and current in our database before comments can be posted. Enter and update disclosures at http://submit.neurology.org. Exception: replies to comments concerning an article you originally authored do not require updated disclosures.
Stay timely. Submit only on articles published within the last 8 weeks.
Do not be redundant. Read any comments already posted on the article prior to submission.
200 words maximum.
5 references maximum. Reference 1 must be the article on which you are commenting.
5 authors maximum. Exception: replies can include all original authors of the article.
Submitted comments are subject to editing and editor review prior to posting.
More guidelines and information on Disputes & Debates
NOTE: The first author must also be the corresponding author of the comment.
I, the first and corresponding author, verify that I have read the contents of the PUBLISHING AGREEMENT form. *
I, the first and corresponding author, verify my disclosures and those of my co-authors are up to date at http://submit.neurology.org. *
Select only one of the three options below: *
I am an Author of this Work, and the Work was prepared on my own time - not as part of my duties as an employee.
I prepared (or cooperated in the preparation of) the Work as part of my duties as an employee, and the Work is, therefore, a "work made for hire", as defined by the United States Copyright Act of 1976, as amended.
I prepared (or participated in the preparation of) the Work as part of my official duties as an officer or employee of the United States Government.
NOTE: All authors, besides the first/corresponding author, must complete a separate Disputes & Debates Submission Form and provide via email to the editorial office before comments can be posted.
Topics Discussed
All Clinical trials
Clinical trials Randomized controlled (CONSORT agreement)
Alert me when this article is cited
Alert me if a correction is posted
Alert me when eletters are published
Ethics Policies
Editors & Editorial Board
AAN Guidelines
Activate a Subscription
Sign up for eAlerts
Visit neurology Template on Facebook
Follow neurology Template on Twitter
Visit Neurology on YouTube
Neurology | Print ISSN:0028-3878
Online ISSN:1526-632X


With summer right around the corner, the weather isn't the only thing heating up in Asheville: festival season is about to kick into high gear. Downtown Asheville boasts a range of festivals to fit just about every interest – and Mosaic Community Lifestyle Realty, an ardent supporter of cultural events that create community, is sponsoring three of the biggest.
Celebrating the toe-tapping music and dance traditions of Southern Appalachia, Shindig on the Green kicks off its 51st season July 1 on Roger McGuire Green at Pack Square in downtown Asheville. Drawing scores of locals and visitors alike, the free event, which will run most Saturdays until Sept. 2, features a stage show and informal jam sessions around the park from 7-10 p.m. With concessions available from Okie Dokies Smokehouse and The Hop Ice Cream Café, you can bring your blanket or lawn chair and make an evening of it, listening to long-standing house band The Stoney Creek Boys and other bluegrass and old-time string bands, and watching cloggers from around Western North Carolina.
Celebrating local community, this popular family-friendly festival brings Downtown Asheville's Pack Square alive on Aug. 4 and 5 with three stages featuring a dynamic range of national, regional and local talent. LEAF Downtown, a free event in its third year, starts early afternoon Friday, and on Saturday kicks off at 9 a.m with an all-ages LEAF Art Dash 5K. Festival-goers can enjoy eats from local food trucks while engaging with family and friends and tuning into a rich range of music including old-time, folk, hip hop, Americana, blues, and deep Appalachian. Rounding out the fun are Easel Rider (Asheville's Mobile Art Lab), costume tents, roaming kids' artists, puppets, jugglers,face-painting, parades and circus arts. Enrichment activities, cultural exchanges, and civic engagement will also take place at the Voices of Asheville Tent through a series of collaborative community alliances. Festivities wind down when the park closes at 10 p.m.


A great water heater is an absolute necessity in any home. Think about all the tasks around the home that require hot water. Whenever you shower, wash your clothes or soak the pots and pans, you need to know that your water heater will provide you with the outstanding performance you need. If you fail to take certain steps to ensure that your water heater is able to do this in an efficient, reliable manner though, you can never count on it. That is why it is so important to schedule professional water heater maintenance. There is just no better way for you to enjoy the most dependable performance that your water heater has to offer. Contact Henson Mechanical Inc today to learn more about why water heater maintenance is so important.
Why is Routine Water Heater Maintenance necessary?
As you heat water for your daily routine and after meal cleanups, your water heater must spring into action. When you drain hot water from your water tank, your water heater must replenish the supply. A tankless water heater heats water on demand, kicking in every single time you call for hot water. All of this use is going to result in some general wear and tear over time. It is very much up to you how much of an impact this wear and tear will have on both the performance and condition of your water heater. If you fail to address it, you can expect a decline in performance quality, higher operating costs, and eventual repair needs. With routine water heater maintenance, though, you can enjoy a reliable, effective performance from your well–tuned water heater.
Not only does your water heater require routine maintenance service to keep it operating properly; it also requires it to operate efficiently. As wear and tear builds up over time, your water heater will have to work harder and harder in order to operate. Sediment may build up in the tank, forcing your water heater to work through this barrier. Of course, the harder your water heater has to work, the more energy it will consume. This means that you will see a rise in your energy costs. Clearly, routine water heater maintenance is a must if you hope to get the performance you want from your water heater.
Your water heater will work more efficiently as a result of routine water heater maintenance. This is not, though, the only way in which scheduling professional water heater maintenance can save you money. Another great benefit of regular water heater maintenance is the reduced repair needs you are likely to encounter.
Ensuring that your water heater is tuned up can help prevent a lot of problems with your water heater, but at some point some issues will develop. Water heater maintenance is a great way for your water heater technician to discover any minor and developing problems before they can cause real damage to your system. If you want to cut down on the risk of water heater damages while also catching any existing problems as soon as possible, routine water heater maintenance service by Henson Mechanical Inc is the way to go.


text:
Europe / Germany / Accommodation /
Hostels in Berlin with Kitchens
Riverside Lodge Berlin
EastSeven Berlin Hostel
Wombats City Hostel Berlin
MEININGER Berlin Alexanderplatz
Berlin, the capital of Germany, is a vibrant city brimming with multicultural communities and living a stylish, laid-back life. Berlin has one of the most turbulent histories of any European capital but has emerged as one of Europe's most popular destinations in recent years. Alcohol is cheap, food is affordable, and accommodation is very reasonable, which is why Berlin is such a hotspot for artists, students, and budget travelers. Berlin is an old city with a young heart and a constant sense of motion. The city offers plenty of outdoor attractions like the Tiergarten and Viktoriapark, and an impressive collection of cutting-edge museums and galleries. Boasting a long history and a very trendy contemporary art scene, there are countless things to do in Berlin.
How much do hostels in Berlin cost?
Average Dorm Price $17 ($2 to $31)
Average Double Private Room Price (in a hostel) $49 ($15 to $91)
See hostels in Berlin from $2
Check Availability HostelWorld.com
Dorm Bed: EUR24.00
Private Room: EUR32.00
Overall Rating: 97%
The Riverside Lodge is one of the most tiny and unique hostel in town. This small hostel is as warm and welcoming as an old friend's hug thanks to its wonderful owners. It has a central, convenient location, just 7 minutes away by metro from downtown attractions such as Alexander Square, Brandenburg Gate, Potsdamer Square and Checkpoint-Charlie, without the noise of the chaotic city center. Found at the heart of in-again Kreuzberg, a neighborhood known for its hip cafes, bars, lively Turkish markets, galleries, street fairs and generally casual atmosphere, near a scenic stretch of the Landwehr canal, the hostel offers a personal, cozy atmosphere in an exciting city. Enjoy clean and incredibly spacious 4-bed mixed rooms with immaculate bathrooms and comfortable beds; keep your personal belongings in huge, easily accessible lockers; ask the friendly staff to help you plan the best route and find the best bars in town and use the free WiFi internet access in the whole property. The Riverside Lodge offers two spacious double rooms with a private kitchen and full bathroom in an apartment next door to the Lodge for 32 euros per person. In addition to free services such as tea and coffee, safe-deposit, luggage storage, shared kitchen, city information, The Riverside Lodge offers linens for 3 euros, towels for 1 euro, bicycle rental, beverages and snacks.
Hobrechtstr 43/corner Maybachufer , Berlin, Germany,
Reviews, Photos, & Prices
Dorm Bed: $26.72
Private Room: $43.59
EastSeven Berlin Hostel has a lovely, relaxed atmosphere where you can feel at home, easily chat to the staff and make new friends. To ensure that you have a fantastic time in Berlin, this medium sized hostel will provide you with friendly, multilingual staff, great location in the centre of Berlin, free WiFi, late check-out, free luggage storage, maps, information and recommendations on where to go, central heating and 24h hot showers! EastSeven Berlin Hostel has a lot of thoughtful little extras like a printer, phone chargers, laundry service, bike rental, happy hour, umbrellas, padlocks and hair dryers. Walking tours leave from the hostel twice a day. They offer an all-you-can-eat continental breakfast with proper Italian coffee and good tea for a very low price or get a voucher for some of the nice cafes in the neighborhood. The hostel is clean and also features a large self-catering kitchen, a cozy lounge, a green and quiet garden and an outdoor BBQ area where it's really easy to meet fellow travellers. The hostel is conveniently located between the hustle and bustle of Mitte, the city's central district and charming Prenzlauer Berg. It's also close to the great bars, clubs, restaurants and shops in Prenzlauer Berg as well as Alexanderplatz and Museum Island. This is the ideal place for travelers seeking the true spirit of Berlin. Choose from double private rooms with shared bathrooms or very comfy beds with reading light, lockers, wall sockets in mixed dorms of 4 and 8 people.
Schwedter Str. 7 , Berlin, Germany,
Wombats City Hostel is located near Alexanderplatz, Museum Island and Prenzlauer Berg. It has a warm family-like atmosphere and a friendly staff with a bunch of tips to give you about the city. The property features a seventh-floor bar with happy hour specials, a rooftop terrace and maximum security with smart card access for the front door, the floors, the rooms and your locker. Located in "Mitte", the most vibrating district of Berlin, Wombats City Hostel is only a 10 minutes walk from major transport hub Alexanderplatz, important sights and a big nightlife scene. A lot of popular restaurants as well as many fashion stores are just around the corner. Enjoy a drink on their amazing rooftop terrace, where you will have an incredible view over the whole city. An all-you-can-eat continental buffet breakfast with organic eggs and fairtrade coffee is available for just 4.50 euros. You don't need to reserve breakfast, just come around to the reception in the morning if you're hungry. Stay in a double private ensuite room or in a mixed ensuite dorm of 4 and 6 beds. The hostel also has apartments with double beds in a separate bedroom, with a kitchen/living room, a double-size sofa and private shower/toilet. All the rooms come with comfy wooden beds, private shower and toilet facilities as well as lockers for your belongings. You'll get a free set of bed linen, a free welcome drink, free Wifi, a guest kitchen and the hostel's free self-made city map with all essential information about the going-ons in town.
Alte Schoenhauser Strasse 2 , Berlin, Germany,
You'll find the Meininger in the middle of Berlin's trendiest district Prenzlauer Berg. The hostel is directly in Senefelderplatz, and forms an ideal starting point for shopping and sightseeing excursions. What makes this district so great is its unique atmosphere generated by the innumerable bars, cafes, restaurants and clubs around the hostel. Whether it's Kollwitzplatz, the Kulturbrauerei, Kastanienallee or Flohmarkt am Mauerpark, the district always offers something that invites you to relax, discover, and have a good time. The Mitte, an equally popular district, where you will find the famous Alexanderplatz and Hackescher Markt, is just a 5 minute stroll away. And those who wish to explore the farther reaches of Berlin will find an U-Bahn-Station on the U2 line, one of the most important underground lines in Berlin, right on the hotel's doorstep. In the lounge, you can put your feet up with a good book after a long day, or enjoy free internet access on your laptop. If you fancy a cool beer and a chat, the chances are you'll find both at the bar. For a match of skills between old or new friends, the Meininger offers a pool table and a foosball. Or you can also sit out on the terrace in front of the building and just take in the colourful bustle of Prenzlauer Berg. Food wise, everybody will find something to their taste, whether it in one of the countless restaurants around the corner, or in the hostel itself. The hostel also features a washing machine, a vending machine and a guest kitchen for you to cook your favourite dish. The Meininger offers accommodation in dormitories as well as single and twin private rooms. All rooms have their own bathroom with a shower and toilet, and are equipped with a TV set. Towels are included only in private rooms and can be rented for 1 euro in dormitories. Free luggage storage is possible on your day of check in and check out and hair dryers are available at the reception for free. You will also find the following available for a small charge: All-You-Can-Eat-And-Drink breakfast buffet for 6,90 euros, tickets for public transport as well as city tours and musicals, late check out until 2pm for 10,00 euros, internet terminals, bicycles, call points for telephone calls, lockers at the reception and pets are allowed for 10 euros per night.
Schönhauser Allee 19 , Berlin, Germany,
Check out other places to stay in amazing destinations around the world.
Quiet and Safe Hostels in BerlinBest Hostels for Solo Travellers in BerlinHostels for Groups in Berlin, GermanyPopular Hostels in Berlin, GermanyBerlin's 5 Best Party Hostels (2019)3 Party Hostels in HamburgAffordable and Safe Hostels in Cologne, GermanyAffordable, Quiet, and Safe Hostels in Hamburg, Germany

redpajama_set_name: RedPajamaCommonCrawl


text:
Oxyrhachis brincki är en insektsart som beskrevs av Capener 1960. Oxyrhachis brincki ingår i släktet Oxyrhachis och familjen hornstritar. Inga underarter finns listade i Catalogue of Life.

Källor

Hornstritar
brincki

redpajama_set_name: RedPajamaWikipedia


text:
Pamela Shamshiri on the Moment She Knew She Wanted to Become a Designer
Life in Design
The AD100 designer opens up about her early design inspiration, favorite projects, and more
By Mallery Roberts Morgan
AD100 designer Pamela Shamshiri in her Los Angeles office.Photography by Trevor Tondro
In a new column, AD PRO contributing editor Mallery Roberts Morgan asks a noteworthy creative to share a defining moment from their life in design.
Pamela Shamshiri and her brother, Ramin, were founding members of Commune Design before they struck out on their own in 2016. In just under four years, their AD100 firm Studio Shamshiri has produced a remarkable number of stunning projects. The studio, located in a classic 1920s building on Sunset Boulevard in Hollywood, is widely admired for its sophisticated take on a California-inflected, bohemian aesthetic. Shamshiri's ability to recognize and elevate the talent of contemporary makers is also a defining element of her style. The studio's work, spanning both commercial and residential, has garnered an enviable client list, ranging from the hippest of Hollywood celebrities to titans of industry. AD PRO sat down with Shamshiri to ask about defining moments in her life, and what impact she thinks the current global crisis will have on the design industry.
AD PRO: Do you remember the moment you knew you wanted to create a life in design?
Pamela Shamshiri: My brother Ramin and I grew up playing in my father's furniture showroom in Tehran. Each floor of the showroom represented a room in a house—dining room, kitchen, living room, et cetera. Things were constantly being moved around and installed. And there were always conversations about why this new kitchen or that piece of furniture was so great. It was pretty much design by osmosis.
Later, when we left Iran and moved to Los Angeles in 1979, my father gave me a set of boxes filled with copies of Architectural Digest he had collected. I specifically remember seeing a story on Pierre Cardin's Bubble Palace and thought, Oh, my God, this is amazing. Giving me those boxes was like passing the torch. I still have them today.
The public-facing Bar Marilou at the Maison de la Luz hotel designed by Studio Shamshiri in New Orleans.
Photo: Stephen Kent Johnson
AD PRO: Tell us about a few projects you feel best represent your work. Were there any unique challenges or aspects of the projects that influenced the design?
PS: Maison de La Luz is a boutique hotel we did in New Orleans that opened last year. I think it really shows the unique process we have at Studio Shamshiri—how we start each project by creating a narrative. We imagined guests coming to town to shoot a movie, play a concert, or just take part in all the energy and festivities of New Orleans. We wanted to create a kind of sanctuary that felt very private—like you were staying in someone's guesthouse. The gathering spaces are intimate, really just for the guests. And then there is the crazy red Bar Marilou where you meet friends—it's open to everyone.
Because the building was an old bank, the staircase was vast and the hallways were wide and incredibly tall. The biggest challenge was how to bring it down to human scale, to make it feel more intimate. We went for a layered, collected, maximalist approach. But as you move upstairs to the suites, everything gets lighter. We wanted guests to feel like they were in a cloud by the time they got into their rooms.
This Rudolph M. Schindler–designed house in L.A. is Shamshiri's own former home.
Photo: Anthony Cotsifas
The Schindler house in L.A. was my own residence until recently. It was a great honor and labor of love to fully renovate and be a steward of this remarkable piece of architecture. The challenge was finding a way to preserve and honor the original vision of Schindler while also making it a great place to live. We chose our moments of slavish restoration and those that were an homage. We talked so much about what Schindler would do, the kids would say, 'Mom! It's like we're living with Schindler!' There were moments of perfect preservation, like the great room, and others like my bathroom that were more of an interpretation. The kitchen became a 40-foot galley, which was not original, but I love cooking with all my friends, and that was a way to do it. I remember arriving at the moment when we decided that we've honored Schindler, and now we need to be the stewards of this home and just live in it.
Finally, a residence in Napa that was 10 years in the making comes to mind. We started it at Commune and finished it at Studio Shamshiri. I'm so proud of this project because it's such a reflection of our clients—their taste, travels, and life together. The interiors are very eclectic in style. I feel if we do our jobs right you can't see us—it's a portrait of the client. I think it's so awkward to put your stamp on someone else's life and expect them to live in it. You really need to embrace who they are.
The house had originally been designed by the late, great decorator Mark Hampton in the '90s. It was a bachelor pad then. When we came in, we were getting it ready for a family. So, it was about embracing everyone's style and collections, bringing it all together. One specific challenge was the epic great room, which is the intersection of all the rooms in the house. We had to figure out how to bring it down to a human scale, to make it a place everyone would want to gather and stay. We painted the ceiling a lavender-blue ombré and created a wainscot effect with wax on the walls, helping to bring the focus down. By covering the big red tile floor with a vast carpet, we resolved issues with sound and created one area for both living and dining.
AD PRO: What is something you are currently working on that excites and inspires you?
PS: We are working on a modular concept for a meditation space that can be applied anywhere. I can't say too much about it, but I'm loving researching monasteries throughout history and across cultures. We're exploring all the different ways to mediate, whether sitting, moving, alone, or in a group.
AD PRO: How do you think what's happening today with the coronavirus pandemic will affect the design industry?
Become an AD PRO Member
Buy now for unlimited access and all of the benefits that only members get to experience.
PS: I think home is going to be more important than ever. We are going to have to live differently. I grew up in Iran, where one is accustomed to living in little compounds. Once you enter, it's its own world. Hopefully we will create more places that are unique to our clients and sanctuaries for them. I've always thought homes should be a place where you recover. At Studio Shamshiri, we have always been very focused on air quality, off-gassing, and not using plastic—I did my thesis on indoor air pollution in grad school! Physical and mental health will definitely be a focus moving forward.


Our Regularly scheduled services give you the ability to maximize your enjoyment while taking the burden of continual cleaning off of your hands. We offer a team of professional pool technicians trained to service your pool or spa and keep it in its top condition. We're committed to providing you with quality service to keep your pool and spa running efficiently. When the colder months come around, our friendly staff can offer winterizations to protect your investment and spring cleaning services to get your pool and spa in its most excellent condition!
Our team can to return your fireplace to its original working condition! Over time fireplaces accumulate dirt, dust, rust, bugs, and all sorts of other surprises. The critters and dirt usually start out as minor issues but are often the source of serious damage and unsafe operating conditions. Regular service will help keep you safe while lengthening the life of your fireplace. Keep your Gas, Wood or Pellet Stove operating safely and efficiently and reduce your energy bills and schedule your maintenance today!


text:
WWSF - Women's Section "Gender equality must become a lived reality"
Prize for women's creativity
Thank You Campaign
8 March Int.Women's Day
WWSF Press Releases
Prize for women's creativity in rural life
2019 - Nomination Letter & Guidelines
Messages from Laureates
List of 442 Prize winners
Laureates 2018
ARYAL Indira - Palpa, Nepal
Working through life's toughest challenges to becoming an important agent of social change
This outstanding and incredibly courageous woman (40), nominated by Apsara Chapagain, former WWSF prize winner from Nepal 2017) has been essentially active in the field of women's rights, in recent years asradio programmer and more recently as station manager of a rural radio station, Radio Lumbini. In a country, which still has very few and poor road communications, the radio is one of the main instruments of change in rural areas. She has actively promoted rural women's empowerment programs on the radio.
Read more: ARYAL Indira - Palpa, Nepal
Asociación de Mujeres Defensores de Vida (AMDV) - Honduras
The courage of fighting for women
AMDV has been an innovative, trail-blazing organization working in very difficult circumstances in one of the most unequal, violent and corrupt countries in the world, where 17% of the population lives in extreme poverty (less than US$1.25 a day).
Read more: Asociación de Mujeres Defensores de Vida (AMDV) - Honduras
ASSOCIATION OF PRO-ACTIVE RURAL WOMEN OF AQUITANIA (ASOMUC) - Colombia
A group of rural women's «divine madness» pays off
A group of rural women's "divine madness":
Aquitania is a municipality with an economy based on the production and marketing of long onions, of which they are the main producer in the country. These have "colonized" the whole region, and in some neighborhoods there are no longer any green areas for children to play or adults to go for walks. This monoculture has only profited a few large landowners, but in no way has it benefitted the quality of life in rural areas, and has even generated very negative impact on Lake Tota due to the amount of fertilizers and pesticides used for this cultivation.
Read more: ASSOCIATION OF PRO-ACTIVE RURAL WOMEN OF AQUITANIA (ASOMUC) - Colombia
AZIZI Ziba Sistan and Baluchestan province, Iran
A powerful role model for women's emancipation
The Laureat (35) is a teacher who has been appointed for her tireless leadership for the education of students in rural areas, especially girls. She has also been addressing and raising awareness on issues like child marriage in her community, where it is still widespread.
Read more: AZIZI Ziba Sistan and Baluchestan province, Iran
BIRUBALA Rabha - Assam, India
A COURAGEOUS OPPONENT of witchhunting
Although this candidate (69) has already been widely acclaimed andhonoured, her nomination is more than merited and would draw attention to what is still a major issue in the Third World and costing worldwide many lives of rural women: sorcery.
Read more: BIRUBALA Rabha - Assam, India
CHAPPAZ Marie-Thérèse Fully, Valais, Switzerland
Passion and creativity create miracles
Marie Thérèse Chappaz (49) from Fully, in the Valais, combines perfectly and in a rare manner the three main criteria of this prize: creativity, innovation and courage. In 20 years, this exceptionally dedicated winegrower has imposed herself as the reference par excellence of Swiss wines for the quality of her wines. The Wine Advocate, possibly the ultimate reference in this field, gave her 99 out of a 100 for two of her wines. She is also a person of great generosity and authenticity that she combines with a disarming modesty.
Read more: CHAPPAZ Marie-Thérèse Fully, Valais, Switzerland
MOSQUERA María Adriana - Los Cerrillos rural community, Colombia
Boundless creativity in changing regional food customs
This is unquestionably one of the most creative and innovative nominations we have received since the prize was created.
The project centers on creating a school garden adapted to climate change, which has had a significant impact on the local community, working with preschoolers in a rural farming community. The goals of the project which have already been reached are to contribute to the future and vitality of rural life in the community through awakening a passion for sustainable agriculture and local and nutritious food among young children who have already started changing eating habits in their homes.
Read more: MOSQUERA María Adriana - Los Cerrillos rural community, Colombia
RAQUEC YAQUí Elvia Leticia Aldea Cruz de Santiago, Tecpan, Guatemala
A powerful promoter of Mayan women's rights
Elvia (34), a woman of Maya Kaqchikel ascent, grew up in a small rural community. At 12, her father took her out of school as she was a girl. Shehowever vowed to show her parents and the community that women, just as men, can study and become professionals. She helpedpay her studies and in addition supported her family by working on the side.
Read more: RAQUEC YAQUí Elvia Leticia Aldea Cruz de Santiago, Tecpan, Guatemala
SAVARIRAJ Pushpa - Tamil Nadu, India
A pioneer of organic cultivation among tribals
Sister Pushpa (35) is a member of St. Joseph's Hill Tribe Development Social Service and Orphanage Society and is a leader and motivator of Tribal Women's Self-Help groups. She has been working with these women since 2008. As a dynamic and talented trainer and resource person who works especially with women and girls, she has made a significant impact. She belongs to the Medical Mission Sisters.
Read more: SAVARIRAJ Pushpa - Tamil Nadu, India
VALDEPEÑA RAMIREZ Aurora & CASTELLANCA RUíZ Teresa Huexca, Morelos, Mexico
An epic fight against a gigantic and destructive barrage
We are suggesting the prize be split between these two indigenous women who are involved in the same struggles against a huge thermo-electrical station being implemented in the region and which has been creating total havoc both on the environment and food chain and in the social structure of the community.
Read more: VALDEPEÑA RAMIREZ Aurora & CASTELLANCA RUíZ Teresa Huexca, Morelos, Mexico


text:
Apple Reportedly Seeking To Buy Cobalt Directly From Miners To Use In Li-Ion Batteries
Alexandra Burlacu, Tech Times 21 February 2018, 10:02 pm
Apple is reportedly seeking to secure its own cobalt supplies directly from miners, as it needs cobalt to make lithium-ion batteries for iPhones and iPads.
If it manages to strike a deal in this respect, Apple would be able to purchase cobalt from miners and ensure a long-term steady supply that would allow it to continue making batteries despite industry concerns of shortages.
Apple In Talks To Buy Cobalt From Miners
According to a new report from Bloomberg, Apple's partner companies in charge of manufacturing batteries for iPhones and iPads are heavily reliant on the availability of cobalt, so Apple reportedly wants to handle this matter itself.
As the electric vehicle market is rapidly expanding, there are industry concerns that cobalt could become increasingly harder to find. Smartphones that pack Li-Ion batteries account for roughly a quarter of cobalt production globally, with a smartphone using roughly eight grams of refined cobalt.
An electric vehicle battery, however, would need more than a 1,000 times that. It means that it may be tough for device makers to source enough cobalt in the future.
Cobalt Supply
The vast majority of cobalt comes from the Democratic Republic of Congo, but the price has been gradually surging. In the past year and a half, cobalt has reached $80,000 per metric ton, which means that its price more than tripled.
Apple is the world's largest cobalt end user, relying on the metal ingredient to make batteries for its mobile devices, but so far it left its metal supply chain in charge of buying the material.
"Apple is seeking contracts to secure several thousand metric tons of cobalt a year for five years or longer," Bloomberg reports, citing sources familiar with the matter.
One source tells Bloomberg that Apple started having talks about potential cobalt deals more than a year ago, but the discussions may not result in an agreement.
The Race To Secure More Cobalt
Several heavyweight companies including BMW, Volkswagen, and Samsung are reportedly racing to secure long-term cobalt deals to ensure they have enough supplies. No major deals are in place yet, but BMW is reportedly close to striking a massive supply deal for a decade.
If Apple manages to reach a multi-year deal with miners to purchase cobalt, it would not only ensure that it has sufficient cobalt supply to meet its targets, but it would also be able to get a better idea of the mining process and the people involved in it. In turn, this would ease concerns regarding child labor as Apple has previously faced scrutiny from human rights organizations over this matter.
Tags: iPhone iPad Li-ion Batteries Cobalt Apple
The Tesla Powerbank Charges Smartphones With Model S Tech, But Is It Worth $45?
Aspark Owl Soars: Japanese Electric Hypercar Goes From 0 To 60 MPH In Less Than 2 Seconds
Rumored iPhone X SE Will Keep Face ID And Notch, But Drop 3D Touch
You Can Get An iPhone Battery Replacement At Office Depot & OfficeMax For $27.99


text:
Glen Iris massage in queens
Gary Valentine Larry Romano When Just massage in Palmerston were starting the show they were just experimenting characters in particular Lisa Rieffel, however she only lasted a few episodes at the start and was never mentioned. Kevin, James and Jerry are known as the main 3 on the show they are in all the promos and should be listed. The MOS has got some flaws particularly when it comes to this. The cast list is meant to surface the entire series as a .
Name: Sharleen
City: Glen Iris
Relation Type: Looking For A Friendsnuggle Buddy Maybe More
Seeking: I Seeking Sexy Meet
A consistent approach works fine.
45 sports massage treatments near toorak
Its rich history Melton top 20 singles also shown it is one of the few treatment forms that can be enjoyed by all members of society as there is often no need for equipment, but rather its success is reliant on a pair of well-trained therapist hands.
Its method is based on manual manipulation of the skin, fascia and soft tissue below to produce both physiological changes within the tissue, as well as a release of endorphins — the natural feel-good neurotransmitter.
Every single activity Prostitutes in Morphett Vale bay been deed to stimulate development and we will share this developmental information with you so each week Bunbury hot moms can take away lots of ideas for supporting and encouraging your baby's development Escort list Gawler home.
You claim that Gladstone house food truck, Leah and Robina chat line free trial numbers are clearly the 3 main" actors, but did you note that Jerry Stiller Craigslist elkins South Brisbane personals Glen Iris massage in queens last?
Before or after class enjoy a coffee at the quaint cafe right next door.
Editors have permission to delete these "External links modified" talk sections if they Dating in the Adelaide Hills to de-clutter talk s, but see the RfC before Glen Iris massage in queens mass Largest dating site Rockhampton removals.
I personally believe this is the way the list should be organised to aid the reader. Overall I cannot see how this method would aid the reader for every single show, those are irrelevant points for the infobox but can be mentioned in the rest of the article. Kelly Hu was only main cast in the pilot episode of TheSara Gilbert was Meet russians in Canberra main cast in 4 episodes of the second season of The Wagga Wagga girls date Bang Theory and the main cast of The Playboy Club were only main cast for 3 episodes.
No special action is required regarding these talk notices, other than regular verification using the archive tool instructions. That's the purpose of the MOS.
Who wrote this article!? Im sure this method works for Massage Ballarat brock road majority of shows which I know about but it is impossible for it to fit. Gary Valentine Larry Romano When they were starting the show they were just experimenting characters in particular Lisa Rieffel, however she only lasted a few episodes at the start and was never mentioned.
Book your next sports massage appointment in toorak with bookwell.
Again, it's not up to us to determine who we think should be listed as starring actors. I see no Tocar massage Richmond why this article alone should be different to every other article.
The position in the list has absolutely Massage midtown new Woodridge connection to perceived importance Chinese massage south beach Glen Iris a particular character.
Experience a relaxing massage like no. What conditions can massage help?
That's original research which is not permitted by policy. That means that there needs to be exceptions that people can agree on.
If you found an error with any archives Glen Iris massage in queens the URLs themselves, you can fix them with this tool. It's not at all unususal for this to happen, or even for characters to be completely recast. This peaceful Glen Iris massage in queens venue has heating and cooling Glen Iris massage in queens ample free onsite parking.
Being replaced by Lee Garlington who was featured in the opening credits of the first episode. In fact, their brain doubles in volume due to connections Asian market downtown Traralgon as a direct result of their activities and experiences.
Baby Sensory is a unique programme specifically deed for babies from birth to 13 months Latino Mandurah dating sites with phone numbers Wagga Wagga to promote Glen Iris massage in queens and development during this precious Rubs massage studio Lismore year.
In season 1 episode 3 he was listed 6th while Larry Romano, who was only in the first 41 of episodes, was listed 4th, yet you don't seem to have issue. As of February"External links Dirty club Mackay talk sections are no longer generated or monitored by InternetArchiveBot.
We need to try and come to a conclusion on this issue as this really Women on ecstasy in Australia work! We don't want readers coming here wondering why somebody is not mentioned in the infobox when they're credited on-screen in a starring role.
However, based on reading the article I've never watched the Bajan singles in Australia as I find Seinfeld to be one of the most overrated TV program s no longer in production it appears that Brull was excluded because the pilot in which she appeared was unaired. There are 2 car parks in 6420 Bunbury ave massage front of the building and numerous parks at the rear which can be accessed by driving down the driveway Osaka Blacktown on the right hand side of the building.
Express massage glen iris
Whatever happened to "guest starring"? It's misleading to not list cast based on an editor's personal opinion.
Customer information:. Call up for your appointment.
It's not misleading to readers to list the people who the producers credited as main cast. This is from Sierra college of beauty Sunbury the readers get most of their information.
She always was just recurring. I. But she was Gay Glen Iris vacations in the pilot and her character was dropped and from the second episode on Mornington muslim dating app it became Julia Louis-Dreyfus who is mentioned in the infobox.
That's 1 less the the episodes of this series in which Lisa Rieffel was main cast. This is a similar situation to the unaired pilot for The Big Bang Theory. Read it twice, thank you. Is there an online database? If an actor is credited as a starring character they are listed as such and, per WP:TVCAST, "Articles should reflect the entire history of a series, and as such actors remain on the list even after their departure from the series".
Terms and Conditions It is now widely recognised that babies learn more during the first year than at any other time in their life.
Massage is one of the oldest, most well known and most practiced of all healing Escorts Albany ms with evidence of its use in many ancient cultures including the Romans, Greeks, Chinese, Egyptians, Japanese and Indians.
Experience a relaxing massage like no .
I'd like to hear from you and who know, maybe we can be friends.
I'm a great believer which you need to try new things in life before you find exactly Asian spas Armidale you enjoy and where you fit best.


text:
15 Feb, 2021 15:52
HomeSport News
'He taught us that "impossible" is just a word': Arnold Schwarzenegger lauds 'idol' Yuri Vlasov after weightlifting legend's death
Russian bodybuilding great Yuri Vlasov (left) with strongman and Hollywood actor Arnold Schwarzenegger © Twitter / Schwarzenegger
Bodybuilding icon and Hollywood superstar Arnold Schwarzenegger has paid tribute to pioneering Soviet and Russian weightlifting champion Yuri Vlasov,who passed away on Saturday at the age of 85 after a hugely influential life.
Schwarzenegger – who saw Vlasov as an idol for his previously unconquered career heights – repeatedly reflected that the Russian weightlifting legend had inspired his love for strength sports.
During his spectacular sporting career, Vlasov claimed four world and six European titles, setting 31 world records and becoming the first weightlifter to clean and jerk more than 200kg.
Under the flag of the Soviet Union, he took gold at the 1960 Summer Games in Rome and silver four years later at the Olympic Games in Tokyo.
A post shared by РУССКИЕ БОЙЦЫ (@russkie_boyci)
A post shared by Паблик о спорте (@sport.best.moments)
Strongman Schwarzenegger's coach introduced him to Vlasov at a 1961 world lifting championship event in Austria, when the Austrian-American was a 14-year-old beginner.
After becoming a film star, Schwarzenegger didn't miss a chance to meet his idol again while filming in Moscow for the 1988 film Red Heat.
The actor insisted on visiting Vlasov, with whom he held an arm-wrestling session in a gym before signing a photo for him which read: "To my idol".
The photograph that A.Schwarzenegger gave to Soviet Olympic champion Yuri Vlasov at their 1988 meeting, signed "To my Idol Yuri Vlasov" pic.twitter.com/LsEAOzW64B
— Soviet Visuals (@sovietvisuals) January 14, 2017
A post shared by TOM™ (@tompari91)
"Yuri Vlasov taught all of us that "impossible" is just a word," gushed the former governor of California.
"He was the first person to clean and jerk 200kg and he inspired me when I met him as a young lifter in 1961. It is because of people like him that I refuse to call myself self-made."
After retiring from sport, poetry lover Vlasov embarked on a literary career, writing dozens of novels that were translated into different languages.
Yuri Vlasov taught all of us that "impossible" is just a word. He was the first person to clean and jerk 200KG, and he inspired me when I met him as a young lifter in 1961. It is because of people like him that I refuse to call myself self-made. 1/ pic.twitter.com/K4qGV0rzEz
— Arnold (@Schwarzenegger) February 15, 2021
When I was lucky enough to really get to know him later, I was blown away. This man wasn't just a great lifter - he was a great thinker. He talked about poetry and politics like a professor, and carried around more books than weights. 2/
He was the head of the Soviet weightlifting federation from 1985 to 1987 before becoming a successful politician and winning election to the State Duma in 1993, later standing as an independent presidential candidate in the 1996 election that was won by Boris Yeltsin.
"When I was lucky enough to really get to know him later, I was blown away," said Schwarzenegger. "This man wasn't just a great lifter - he was a great thinker.
"He talked about poetry and politics like a professor and carried around more books than weights. He told me the power of the body was nothing compared to the power of the mind.
He told me the power of the body was nothing compared to the power of the mind. He was one of the strongest men in the world and he believed that real strength came from words. 3/
He was truly one of a kind and I hope each and every one of us can find inspiration in his story. I was lucky to know him and I will miss him dearly. My thoughts are with his family. 4/4
"He was one of the strongest men in the world and he believed that real strength came from words. He was truly one of a kind and I hope each and every one of us can find inspiration in his story.
"I was lucky to know him and I will miss him dearly. My thoughts are with his family."
Organizers will dedicate the 2021 European Weightlifting Championships, scheduled to take place in Moscow from April 3 to 11, to the memory of Vlasov.
Also on rt.com 'Leave Gina Carano alone!' UFC's Dana White on 'anti-semitic' posts, MMA journo Helwani responds to 'douche' comments
ArnoldSchwarzeneggernews
Arnold SchwarzeneggerHollywood moviesOlympics
15 minutes of infamy? LeBron James heckler Juliana Carlos – aka 'Courtside Karen' – faces calls to be BANNED from NBA games
'Fat man is going to die sh*tting himself': Maradona's daughter says she 'vomited' after hearing doctors discuss football legend


Sealants are one of the best and simplest ways to protect teeth from decay. Many patients we see are born with or develop very deep grooves and pits in their teeth. Some of these areas are too small for even a single toothbrush bristle to access, but they're big enough for bacteria to colonize. As bacteria access these difficult to clean areas of teeth, they continue to absorb nutrients from food and drink and excrete a sticky, acidic biofilm known as plaque. Over time, plaque weakens tooth enamel and may lead to tooth decay. Children especially have difficulty brushing and flossing thoroughly enough to prevent decay in these deep pits and grooves. That's where dental sealants from Rogersville Family Dentistry come in. The thin, clear coat of plastic protects teeth from decay-causing bacteria. Contact our team to find out more or ask about dental sealants at your next six month checkup.
Before we place dental sealants, we want to make sure your smile is completely healthy. We diagnose, treat, and repair any current oral health concerns. Once patients achieve their healthiest smile, we apply a thin coat of sealant material to the surface of teeth. The sealant is then hardened in place with a curing light. Once in place, dental sealants create a barrier between tooth enamel and destructive bacteria that can protect teeth for years, keeping smiles whole and healthy and reducing risk for more severe oral health issues down the line.


text:
Albury Regional Art Gallery
The Albury Regional Art Gallery, located in Dean St, comprises 2 extant historic buildings that are listed on the local government heritage overlay: the old Albury Town Hall and Burrows House. Albury City Council is planning to redevelop the site and engaged ArchLink to conduct an archaeological assessment towards the end of 2013.
Background research discovered that the site has been utilised for a number of purposes over the years including the town's courthouse, a telegraph station, and the Crown Lands and Survey Office. It therefore possesses occupation phases relating to a larger civic precinct that has been an integral part of central Albury since 1847.
An archaeological excavation and monitoring program was undertaken prior to and during the building demolition and construction works. Deposits from the Town Hall and Municipal Office periods of occupation (1907-1920s) were encountered under the floorboards in which was found old cigarette packets, paper envelopes, pins, paper clips and other discarded objects. Under a layer of capping clay older deposits of demolition material were encountered between stone foundations – the remains of the Telegraph Station building that stood here before the Town Hall (1867-1907). Artefacts found amongst the broken bricks included slate pencils, pins, pen nibs, buttons and other small objects. The findings indicated that the brick walls of the Telegraph building had been completely demolished down to the base of the stone foundations in most places.
Interestingly, the early water storage system for the Telegraph Station was found comprising a brick well and two underground brick tanks with terracotta pipes that would have carried water from the well, and also from two down pipe pits, to the tanks. The remains of a stable comprising stone walls and heavily worn brick flooring was also located at the rear of the property.


In a small house on a quiet, tree-lined street behind one of the main shopping malls in Lusaka, Zambia, young people are coming together to learn technology skills, share ideas and be part of a community dedicated to the ideals of innovation, creativity and sustainability.
Started by four local entrepreneurs in 2011, BongoHive provides out-of-the-box technological solutions that can be applied in economics, business, health, education and many other areas. Across Africa, innovation hubs like BongoHive are preparing young people for the job market and giving them an opportunity to contribute to society.
This short film was produced by UNICEF's Office of Research – Innocenti in 2014 to support The State of the World's Children.


text:
import { forEach } from 'lodash'

/**
 * Utility class used when clustering points into MultiPoint objects
 */

export default class PointCluster {
  constructor() {
    this.points = []
  }

  addPoint(point) {
    if (this.points.indexOf(point) === -1) this.points.push(point)
  }

  mergeVertices(graph) {
    const vertices = []
    forEach(this.points, (point) => {
      vertices.push(point.graphVertex)
    })
    graph.mergeVertices(vertices)
  }
}

redpajama_set_name: RedPajamaGithub