scholarly journals High rate of extrapair paternity in a human population demonstrates diversity in human reproductive strategies

2020 ◽  
Vol 6 (8) ◽  
pp. eaay6195 ◽  
Author(s):  
B. A. Scelza ◽  
S. P. Prall ◽  
N. Swinford ◽  
S. Gopalan ◽  
E. G. Atkinson ◽  
...  
Keyword(s):  
High Rate ◽  
Human Populations ◽  
Social Monogamy ◽  
Double Blind ◽  
Extrapair Paternity ◽  
Human Reproductive ◽  
Double Blind Method ◽  
Almost All ◽  
Range Of Variation ◽  
Nonhuman Species

Among nonhuman species, social monogamy is rarely accompanied by complete fidelity. Evolutionary theory predicts that the rate of extrapair paternity (EPP) should vary according to socioecological conditions. In humans, however, geneticists contend that EPP is negligible and relatively invariable. This conclusion is based on a limited set of studies, almost all of which describe European-descent groups. Using a novel, double-blind method designed in collaboration with a community of Himba pastoralists, we find that the rate of EPP in this population is 48%, with 70% of couples having at least one EPP child. Both men and women were very accurate at detecting cases of EPP. These data suggest that the range of variation in EPP across human populations is substantially greater than previously thought. We further show that a high rate of EPP can be accompanied by high paternity confidence, which highlights the importance of disaggregating EPP from the notion of “cuckoldry.”

Final results from ClarIDHy, a global, phase 3, randomized, double-blind study of ivosidenib (IVO) versus placebo (PBO) in patients (pts) with previously treated cholangiocarcinoma (CCA) and an isocitrate dehydrogenase 1 (IDH1) mutation.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 4069-4069
Author(s):  
Ghassan K. Abou-Alfa ◽  
Teresa Macarulla ◽  
Milind M. Javle ◽  
Robin Kate Kelley ◽  
Sam Joseph Lubner ◽  
...  
Keyword(s):  
Quality Of Life ◽  
Primary Endpoint ◽  
Failure Time ◽  
Objective Response ◽  
Idh1 Mutation ◽  
High Rate ◽  
Double Blind Study ◽  
Double Blind ◽  
Grade 3

4069 Background: CCA is a rare cancer for which there are limited effective therapies. IDH1 mutations occur in ̃20% of intrahepatic CCAs, resulting in production of the oncometabolite D-2-hydroxyglutarate, which promotes oncogenesis. IVO (AG-120) is a first-in-class, oral, small-molecule inhibitor of mutant IDH1 (mIDH1). ClarIDHy aimed to demonstrate the efficacy of IVO vs PBO in pts with unresectable or metastatic m IDH1 CCA. The primary endpoint was met with significant improvement in progression-free survival (PFS) by independent radiology center (IRC) with IVO vs PBO (hazard ratio [HR] = 0.37, p < 0.0001). Objective response rate (ORR) and stable disease for IVO were 2.4% (3 partial responses) and 50.8% (n = 63) vs 0% and 27.9% (n = 17) for PBO. IVO pts experienced significantly less decline in physical and emotional functioning domains of quality of life at cycle 2 day 1 vs PBO pts (nominal p < 0.05). Methods: Pts with m IDH1 CCA were randomized 2:1 to IVO (500 mg PO QD) or matched PBO and stratified by prior systemic therapies (1 or 2). Key eligibility: unresectable or metastatic m IDH1 CCA based on central testing; ECOG PS 0–1; measurable disease (RECIST v1.1). Crossover from PBO to IVO was permitted at radiographic progression. Primary endpoint: PFS by IRC. Secondary endpoints included overall survival (OS; by intent-to-treat), ORR, PFS (by investigator), safety, and quality of life. The planned crossover-adjusted OS was derived using the rank-preserving structural failure time (RPSFT) model. Results: As of 31 May 2020, ̃780 pts were prescreened for an IDH1 mutation and 187 were randomized to IVO (n = 126) or PBO (n = 61); 13 remain on IVO. Median age 62 y; M/F 68/119; 91% intrahepatic CCA; 93% metastatic disease; 47% had 2 prior therapies. 70% of PBO pts crossed over to IVO. OS data were mature, with 79% OS events in IVO arm and 82% in PBO. Median OS (mOS) was 10.3 months for IVO and 7.5 months for PBO (HR = 0.79; 95% CI 0.56–1.12; one-sided p = 0.093). The RPSFT-adjusted mOS was 5.1 months for PBO (HR = 0.49; 95% CI 0.34–0.70; p < 0.0001). Common all-grade treatment emergent adverse events (TEAEs, ≥ 15%) in the IVO arm: nausea 41%, diarrhea 35%, fatigue 31%, cough 25%, abdominal pain 24%, decreased appetite 24%, ascites 23%, vomiting 23%, anemia 18%, and constipation 15%. Grade ≥ 3 TEAEs were reported in 50% of IVO pts vs 37% of PBO pts, with grade ≥ 3 treatment-related AEs in 7% of IVO pts vs 0% in PBO. 7% of IVO pts experienced an AE leading to treatment discontinuation vs 9% of PBO pts. There were no treatment-related deaths. Conclusions: IVO was well tolerated and resulted in a favorable OS trend vs PBO despite a high rate of crossover. These data – coupled with statistical improvement in PFS, supportive quality of life data, and favorable safety profile – demonstrate the clinical benefit of IVO in advanced m IDH1 CCA. Clinical trial information: NCT02989857.

Comparative Efficacy and Safety of Sertraline Versus Nortriptyline in Major Depression in Patients 70 and Older

1999 ◽  
Vol 11 (1) ◽  
pp. 85-99 ◽  
Author(s):  
Sanford I. Finkel ◽  
Ellen M. Richter ◽  
Cathryn M. Clary
Keyword(s):  
Major Depression ◽  
Rating Scale ◽  
Antidepressant Treatment ◽  
Change Score ◽  
Attrition Rate ◽  
Double Blind ◽  
Almost All ◽  
Positive Effect ◽  
Population Segment

Background. Few randomized, double-blind studies that examine antidepressant treatment in patients 70 years and older are available. To provide additional data on the safety and efficacy of antidepressants in this rapidly growing population segment, a subgroup analysis of a larger sertraline vs. nortriptyline elderly depression treatment study was performed. Methods. Outpatients (N = 76) who met DSM-III-R criteria for major depression with a minimum Hamilton Depression Rating Scale (HAM-D) severity score of 18 were randomized to 12 weeks of flexible dose treatment with sertraline (50–150 mg) or nortriptyline (25–100 mg). Results. Both treatments significantly improved depression as measured by the HAM-D and Clinical Global Impression scales. At Weeks 10, 12, and endpoint, sertraline demonstrated a significantly greater reduction in depression severity compared to nortriptyline as measured by improvement on the 24-item HAM-D (mean adjusted change score of 14.8 vs. 7.6, respectively, at Week 12; p = .001). Sixty-five percent of sertraline-treated patients were responders by Week 12 (50% or greater reduction from baseline in 24-item HAM-D score) compared to 26% of nortriptyline-treated patients (p < .05). Sertraline treatment had a significantly more positive effect, when compared to nortriptyline, across almost all associated measures of cognitive function, energy, anxiety, and quality of life and was better tolerated than nortriptyline, with a lower attrition rate/side effect burden. Conclusion. The efficacy advantage of sertraline appeared to be even greater in this subgroup of older patients drawn from a larger treatment study of depression that included elderly individuals over the age of 60.

BINDING OF 17-SUBSTITUTED 16-NITRILE 16,17-SECOESTRANE COMPOUNDS TO ESTROGEN RECEPTORS – „IN VITRO“ AND „IN SILICO“ STUDY

2021 ◽  
Author(s):  
Suzana S. Jovanović-Šanta ◽  
◽  
Esma Isenović ◽  
Julijana A. Petrović ◽  
Yaraslau U. Dzichenka
Keyword(s):  
Amino Acids ◽  
Estrogen Receptors ◽  
Nuclear Translocation ◽  
Binding Mode ◽  
High Rate ◽  
Dynamics Simulation ◽  
Breast Cancers ◽  
Number Of Binding Sites ◽  
Almost All

About 75% of breast cancers express estrogen receptors (ERs), which is a good base for an efficient endocrine therapy. This gives the opportunity for the treatment of patients with antiestrogens, compounds that bind to the ERs and thus compete to estradiol (E2), preventing its action in progression of estrogen-depending cancers. Here we present results of testing the effect of the modified steroids, namely 17-substituted 16-nitrile 16,17-secoestrane compounds on the E2-ER complex forming, its stability, nuclear translocation and binding to DNA. Almost all compounds in moderate to high rate induced lower forming of this complex, destabilizing it – they increased Kd of this complex and decreased number of binding sites. Complex formed in the presence of some test secosteroids could pass to the nucleus, while other compounds inhibited translocation. In the presence of some compounds binding of the formed complex E2-ER to DNA was noticed. Docking followed molecular dynamics simulation was performed to reveal binding mode of E2 to ER in the presence of test secosteroids. Amino acids important for binding process and complex stabilization were detected. Analysis of the simulation data allowed identifying key amino acids and type of binding of the secoestrane compounds, important for high affinity binding of the steroidal compounds.

Coronavirus and Fingerprint Technology

2021 ◽  
Vol 13 (4) ◽  
pp. 1-16
Author(s):  
Gabriel B. Iwasokun
Keyword(s):  
Severe Acute Respiratory Syndrome ◽  
Viral Infection ◽  
Virus Disease ◽  
High Rate ◽  
Corona Virus ◽  
The World ◽  
Almost All

The corona virus disease, otherwise known as COVID-19, is an extremely communicable and pathogenic viral infection caused by severe acute respiratory syndrome corona virus 2 (SARS-CoV-2), which emerged in Wuhan, China in December 2019 and has spread to almost all the countries in the world. The transmission of the virus is through touching of the nose, eyes, or mouth by a finger that has been contaminated through droplets on a surface when a carrier sneezes or coughs. Since the existing fingerprint devices are predominantly contact based, it implies that they can aid in the transmission of the virus. This paper discusses the application of fingerprint devices in notable places with high rate of COVID-19 infection as well as the threats to fingerprint technologies and the countermeasures. The need to change focus and orientation towards contactless biometric technologies as sure solution to the fear and animosity expressed towards contact-based fingerprint technology is also expatiated.

Use of antidepressants in patients with depression and comorbid diabetes mellitus: a systematic review

2016 ◽  
Vol 29 (3) ◽  
pp. 127-139 ◽  
Author(s):  
Subethini Roopan ◽  
Erik Roj Larsen
Keyword(s):  
Diabetes Mellitus ◽  
Maintenance Phase ◽  
Tricyclic Antidepressant ◽  
Favourable Effect ◽  
Strong Impact ◽  
Double Blind ◽  
Patients With Diabetes ◽  
Randomised Controlled ◽  
Almost All ◽  
Design And Methods

ObjectiveDepression may be difficult to treat and with comorbid diabetes mellitus (DM) it is an even bigger challenge. This article aims to evaluate antidepressants most suitable for patients with depression and comorbid DM.Design and methodsInitially we searched for randomised, controlled double-blind trials of treatment with antidepressants in depressed with DM but there were only a few studies and many of them were small trials. Thus, we decided to include studies that were not only randomised-controlled trials. In total, we ended up with 18 articles for our purposes.ResultsThe combination of depression and DM may be harmful as depression has a strong impact on psychosocial and medical outcomes in patients with DM. Almost all of the trials in this review showed a reduction in depressive symptoms after treatment with an antidepressant in the acute as well as during maintenance phase. It showed that depression improvement had a favourable effect on glycaemic control that was weight independent. Some studies included only subjects with minor depression or with suboptimal-controlled diabetes making it difficult to show an effect.ConclusionFrom these data, we will recommend choosing an selective serotonin reuptake inhibitor (SSRI) if possible to treat a depression among patients with diabetes. If treatment with a tricyclic antidepressant is needed, closer glycaemic monitoring is recommended. Bear in mind that there is a possible risk of hypoglycemia when using SSRIs. Agomelatine and bupropion have shown promising results, but need to be investigated in more trials.

scholarly journals Boater Safety: Communicating Weather Forecast Information to High-Stakes End Users

2012 ◽  
Vol 4 (1) ◽  
pp. 7-19 ◽  
Author(s):  
Sonia Savelli ◽  
Susan Joslyn
Keyword(s):  
Pacific Northwest ◽  
Online Survey ◽  
Puget Sound ◽  
Weather Forecast ◽  
High Rate ◽  
False Alarms ◽  
High Stakes ◽  
Precautionary Action ◽  
Time Of Year ◽  
Almost All

Abstract Recreational boaters in the Pacific Northwest understand that there is uncertainty inherent in deterministic forecasts as well as some of the factors that increase uncertainty. This was determined in an online survey of 166 boaters in the Puget Sound area. Understanding was probed using questions that asked respondents what they expected to observe when given a deterministic forecast with a specified lead time, for a particular weather parameter, during a particular time of year. It was also probed by asking respondents to estimate the number of observations, out of 100 or out of 10, that they expected to fall within specified ranges around the deterministic forecast. Almost all respondents anticipated some uncertainty in the deterministic forecast as well as specific biases, most of which were born out by an analysis of local National Weather Service verification data. Interestingly, uncertainty and biases were anticipated for categorical forecasts indicating a range of values as well, suggesting that specifying numeric uncertainty would improve understanding. Furthermore, respondents’ answers suggested that they expected a high rate of false alarms among warning and advisory forecasts. Nonetheless, boaters indicated that they would take precautionary action in response to such warnings, in proportions related to the size of boat they were operating. This suggests that uncertainty forecasts would be useful to these experienced forecast consumers, allowing them to adapt the forecast to their specific boating situation with greater confidence.

scholarly journals Revisiting comorbidities in gout: a cluster analysis

2013 ◽  
Vol 74 (1) ◽  
pp. 142-147 ◽  
Author(s):  
Pascal Richette ◽  
Pierre Clerson ◽  
Laure Périssin ◽  
René-Marc Flipo ◽  
Thomas Bardin
Keyword(s):  
Cluster Analysis ◽  
Renal Failure ◽  
Large Cohort ◽  
High Rate ◽  
Cross Sectional ◽  
High Prevalence ◽  
History Of ◽  
Obesity Hypertension ◽  
Almost All

ObjectivesThe reciprocal links between comorbidities and gout are complex. We used cluster analysis to attempt to identify different phenotypes on the basis of comorbidities in a large cohort of patients with gout.MethodsThis was a cross-sectional multicentre study of 2763 gout patients conducted from November 2010 to May 2011. Cluster analysis was conducted separately for variables and for observations in patients, measuring proximity between variables and identifying homogeneous subgroups of patients. Variables used in both analyses were hypertension, obesity, diabetes, dyslipidaemia, heart failure, coronary heart disease, renal failure, liver disorders and cancer.ResultsComorbidities were common in this large cohort of patients with gout. Abdominal obesity, hypertension, metabolic syndrome and dyslipidaemia increased with gout duration, even after adjustment for age and sex. Five clusters (C1–C5) were found. Cluster C1 (n=332, 12%) consisted of patients with isolated gout and few comorbidities. In C2 (n=483, 17%), all patients were obese, with a high prevalence of hypertension. C3 (n=664, 24%) had the greatest proportion of patients with type 2 diabetes (75%). In C4 (n=782, 28%), almost all patients presented with dyslipidaemia (98%). Finally, C5 (n=502, 18%) consisted of almost all patients with a history of cardiovascular disease and renal failure, with a high rate of patients receiving diuretics.ConclusionsCluster analysis of comorbidities in gout allowed us to identify five different clinical phenotypes, which may reflect different pathophysiological processes in gout.

CCTV and robbery in high-rise public housing in Hong Kong

2020 ◽  
Vol 19 (3) ◽  
pp. 119-130
Author(s):  
Lina Chow ◽  
Rob I. Mawby
Keyword(s):  
Hong Kong ◽  
High Rate ◽  
Community Safety ◽  
Content Type ◽  
High Rise ◽  
Police Statistics ◽  
Almost All ◽  
The Impact ◽  
Industrial Societies ◽  
Practical Implications

Purpose In Hong Kong, robberies occurring in the elevators in high-rise buildings were identified as a particular problem and the purpose of this paper is to address a dedicated programme aimed at reducing such offences. Design/methodology/approach A comparison of elevator-based robbery statistics over a ten-year policy-implication period, in two police districts, one with a high rate of public ownership and a traditionally high rate of elevator robberies, the second with a higher rate of private ownership and a traditionally lower rate of such robberies. Findings The evidence suggests that the programme was successful, with such robberies declining significantly and with no evidence of displacement. Research limitations/implications This research is based on police statistics. There is a need for more research, for example, investigating residents’ involvement with the system and the extent to which it encouraged shared ownership of the initiative. Practical implications What is clear is that, where in the West the Newman legacy led to the demonisation of high-rise public sector housing, in Hong Kong, where there is no viable alternative, the use of CCTV helped transform such areas into safer communities. Social implications The rate of robbery, most notably elevator-based robbery, fell dramatically, improving community safety. Originality/value Though there has been a considerable amount of research on the impact of CCTV on crime, almost all of this has focussed on Western industrial societies and little of it has addressed robbery. To the best of authors’ knowledge, this research is the first in Hong Kong, and the first to evaluate the impact of CCTV on robbery.

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