To investigate the selective agents that shape signals, we examined function (adaptive benefit to signaler) in the boom loud call by male blue monkeys. Using natural observation and playbacks in a ...wild population in Kenya, we characterized boom function from conspecifics' behavioral responses and also variation in call usage relating to context and reproductive season. Booms occurred in several contexts and after varied stimuli, including falling branches, yet were strongly associated with intragroup activity and, in particular, affiliative interactions between callers and females. Males produced more booms during the mating season and, congruently, when more females in their groups were sexually active. After hearing booms, compared to no call, females spent more time near groupmates and the caller and were more likely to approach and have mating interactions with him. Males tended to move away after hearing a boom. In the aggregate, results indicate that booms achieve multiple functions relating to facilitating group cohesion, affiliative interactions, and mating opportunities, while also repelling rival males. An observed association with falling branches is puzzlingly distinct from these social functions. We explore the hypothesis that booms enable affiliative encounters by acting as signals of benign intent, and discuss the functional versatility of signals perceived by multiple receivers that vary in age, sex, and relationship to signalers.
Signals that occur in multiple contexts and evoke varied responses from receivers underscore the challenges of assessing a signal's function (adaptive benefit to signaler) or relationships between ...receivers' responses and their own fitness. Our study investigated the "pyow" loud call of male blue monkeys in a wild population in western Kenya. Using natural observation and playback experiments, we characterized pyow function based on behavioral responses by adult male and female receivers, and contextual, seasonal, and demographic variation in call usage. To identify associations between call features and traits of callers (signal concordance), we examined pyows' usage patterns and acoustic structure in relation to attributes of callers. Pyows occurred in association with numerous stimuli and contexts, including predators, other males, intergroup aggression, and often "spontaneously," and were more frequent in the mating season. Receivers consistently oriented toward calls and increased scanning, but other responses differed by sex—females moved toward and spent more time near the caller and groupmates, whereas males retreated. Pyows exhibited concordance with identity and social status, but were not associated with callers' attention to any particular external entity. Results indicate pyows achieve multiple functions, including mate defense, group cohesion, and mate attraction. The call's functional versatility appears best explained by its ability to draw attention and that receivers' subsequent behavior is consistent with their own fitness priorities relevant to the caller's identity, status, and context of calling.
This study describes imaging features of diffuse intrinsic pontine glioma (DIPG) and correlates with overall survival (OS) and histone mutation status in the International DIPG Registry (IDIPGR).
...Four hundred cases submitted to the IDIPGR with a local diagnosis of DIPG and baseline MRI were evaluated by consensus review of 2 neuroradiologists; 43 cases were excluded (inadequate imaging or alternative diagnoses). Agreement between reviewers, association with histone status, and univariable and multivariable analyses relative to OS were assessed.
On univariable analysis imaging features significantly associated with worse OS included: extrapontine extension, larger size, enhancement, necrosis, diffusion restriction, and distant disease. On central review, 9.5% of patients were considered not to have DIPG. There was moderate mean agreement of MRI features between reviewers. On multivariable analysis, chemotherapy, age, and distant disease were predictors of OS. There was no difference in OS between wild-type and H3 mutated cases. The only imaging feature associated with histone status was the presence of ill-defined signal infiltrating pontine fibers.
Baseline imaging features are assessed in the IDIPGR. There was a 9.5% discordance in DIPG diagnosis between local and central review, demonstrating need for central imaging confirmation for prospective trials. Although several imaging features were significantly associated with OS (univariable), only age and distant disease were significant on multivariable analyses. There was limited association of imaging features with histone mutation status, although numbers are small and evaluation exploratory.
In June 2007, a previously undescribed monkey known locally as "lesula" was found in the forests of the middle Lomami Basin in central Democratic Republic of Congo (DRC). We describe this new species ...as Cercopithecus lomamiensis sp. nov., and provide data on its distribution, morphology, genetics, ecology and behavior. C. lomamiensis is restricted to the lowland rain forests of central DRC between the middle Lomami and the upper Tshuapa Rivers. Morphological and molecular data confirm that C. lomamiensis is distinct from its nearest congener, C. hamlyni, from which it is separated geographically by both the Congo (Lualaba) and the Lomami Rivers. C. lomamiensis, like C. hamlyni, is semi-terrestrial with a diet containing terrestrial herbaceous vegetation. The discovery of C. lomamiensis highlights the biogeographic significance and importance for conservation of central Congo's interfluvial TL2 region, defined from the upper Tshuapa River through the Lomami Basin to the Congo (Lualaba) River. The TL2 region has been found to contain a high diversity of anthropoid primates including three forms, in addition to C. lomamiensis, that are endemic to the area. We recommend the common name, lesula, for this new species, as it is the vernacular name used over most of its known range.
Mineworkers in Southern Africa have the highest rates of tuberculosis (TB) among working populations in the world (The World Bank, Benefits and costs associated with reducing tuberculosis among ...Southern Africa's mineworkers, 2014), making mineworkers a key population for TB program efforts. The current evaluation aimed to characterize mineworkers and former (ex-) mineworkers, and assess knowledge, attitudes and practices related to TB and HIV care among mineworkers and healthcare workers (HCWs) in Zambia.
A mixed-methods evaluation of current and former (ex-) mineworkers and HCWs was conducted in the Copperbelt and North-Western provinces, Zambia. Knowledge, attitudes and practices (KAPs) related to TB care and policies were assessed using a structured survey. Focus Group Discussions (FGDs) were conducted with current and ex-mineworkers to understand perceptions, practices, and barriers related to accessing healthcare for TB.
Overall, 2,792 mineworkers and 94 HCWs completed the KAP survey, and 206 (171 current, 71 ex-) mineworkers participated in FGDs. Mineworkers and ex-mineworkers were knowledgeable about TB symptoms (cough; 94%), transmission (81.7%) and treatment (99.2%). Yet, barriers to seeking care were evident with 30% of mineworkers experiencing cough, and 19% reporting 2 or more TB symptoms at the time of the survey. The majority of mineworkers (70.9%) were aware of policies barring persons from working after a diagnosis of TB, and themes from FGDs and HCW comments (n = 32/62; 51.6%) recognized fear of job loss as a critical barrier to providing timely screening and appropriate care for TB among mineworkers. The majority (76.9%) of mineworkers indicated they would not disclose their TB status to their supervisor, but would be willing to share their diagnosis with their spouse (73.8%).
Fear of job loss, driven by governmental policy and mistrust in mining companies, is a major barrier to healthcare access for TB among mineworkers in Zambia. As a result of these findings, the government policy prohibiting persons from working in the mines following TB disease is being repealed. However, major reforms are urgently needed to mitigate TB among mineworkers, including ensuring the rights of mineworkers and their communities to healthy living and working environments, improved social responsibility of mining companies, and facilitating choice and access to affordable, timely, and high-quality healthcare services.
Evidence for a role for vitamin D in non-alcoholic fatty liver disease (NAFLD) pathogenesis is conflicting. As Mendelian randomisation (MR) avoids many limitations of conventional observational ...studies, this two-sample bidirectional MR analysis was conducted to determine the following: (i) whether genetically predicted 25-hydroxyvitamin D 25(OH)D levels are a risk factor for NAFLD, and (ii) whether genetic risk for NAFLD influences 25(OH)D levels. Single-nucleotide polymorphisms (SNPs) associated with serum 25(OH)D levels were obtained from the European ancestry-derived SUNLIGHT consortium. SNPs associated with NAFLD or NASH (
-value < 1 × 10
) were extracted from previous studies and supplemented by genome-wide association studies (GWASs) performed in the UK Biobank. These GWASs were done both without (primary analysis) and with (sensitivity analysis) the population-level exclusion of other liver diseases (e.g., alcoholic liver diseases, toxic liver diseases, viral hepatitis, etc.). Subsequently, MR analyses were performed to obtain effect estimates using inverse variance weighted (IVW) random effect models. Cochran's Q statistic, MR-Egger regression intercept, MR pleiotropy residual sum and outlier (MR-PRESSO) analyses were used to assess pleiotropy. No causal association of genetically predicted serum 25(OH)D (per standard deviation increase) with risk of NAFLD was identified in either the primary analysis:
= 2757 cases,
= 460,161 controls, odds ratio (95% confidence interval): 0.95 (0.76, -1.18),
= 0.614; or the sensitivity analysis. Reciprocally, no causal association was identified between the genetic risk of NAFLD and serum 25(OH)D levels, OR = 1.00 (0.99, 1.02,
= 0.665). In conclusion, this MR analysis found no evidence of an association between serum 25(OH)D levels and NAFLD in a large European cohort.
Infanticide by males is widespread across mammals and especially prevalent among primates. Considerable research has examined how fitness benefits can explain the occurrence of this behavior; less is ...known, however, about intrapopulation variation in its occurrence. We evaluated 10 infanticides by males in wild blue monkeys according to the sexual selection hypothesis. To explore intrapopulation variation in occurrence of infanticide, we compared these cases to 38 cases that were contextually similar but in which infanticide did not occur. We examined male reproductive benefit, infant age, maternal parity, postconception estrus, group defense, available mating partners, and context of takeover. We based comparisons on daily or near daily records of male presence in the study groups, infant birth dates, and male-female sexual interactions. Infanticides followed predictions of the sexual selection hypothesis: males were unlikely to kill their own offspring, the period for the mother's return to conception was reduced by half, and males increased their chance of siring her next offspring. Difference in male reproductive benefit, costs, and motivation did not fully explain the observed variation in infanticide occurrence. Infants were more likely to be spared if they were older when a male first arrived, or if their mother had mated with the male in the second month after conception. The most important determinant of infant fate, however, was male identity, a finding consistent with 2 scenarios: 1) an infanticidal tendency may be influenced by a genetic polymorphism that is not fixed in this population or 2) infanticidal behavior may be a conditional male strategy. Further research on intrapopulation variation in infanticidal behavior should focus especially on characteristics of males.
Purpose
Rasmussen encephalitis (RE) is a very rare chronic neurological disorder of unilateral inflammation of the cerebral cortex. Hemispherotomy provides the best chance at achieving seizure ...freedom in RE patients, but with significant risks and variable long-term outcomes. The goal of this study is to utilize our multicenter pediatric cohort to characterize if differences in pathology and/or imaging characterization of RE may provide a window into post-operative seizure outcomes, which in turn could guide decision-making for parents and healthcare providers.
Methods
This multi-institutional retrospective review of medical record, imaging, and pathology samples was approved by each individual institution’s review board. Data was collected from all known pediatric cases of peri-insular functional hemispherotomy from the earliest available electronic medical records. Mean follow-up time was 4.9 years. Clinical outcomes were measured by last follow-up visit using both Engel and ILAE scoring systems. Relationships between categorical and continuous variables were analyzed with Pearson correlation values.
Results
Twenty-seven patients met study criteria. No statistically significant correlations existed between patient imaging and pathology data. Pathology stage, MRI brain imaging stages, and a combined assessment of pathology and imaging stages showed no statistically significant correlation to post-operative seizure freedom rates. Hemispherectomy Outcome Prediction Scale scoring demonstrated seizure freedom in only 71% of patients receiving a score of 1 and 36% of patients receiving a score of 2 which were substantially lower than predicted.
Conclusions
Our analysis did not find evidence for either independent or combined analysis of imaging and pathology staging being predictive for post peri-insular hemispherotomy seizure outcomes, prompting the need for other biomarkers to be explored. Our data stands in contrast to the recently proposed Hemispherectomy Outcome Prediction Scale and does not externally validate this metric for an RE cohort.
Purpose
Anti-PD-1 therapy provides clinical benefit in 40–50% of patients with relapsed and/or metastatic head and neck squamous cell carcinoma (RM-HNSCC). Selection of anti- PD-1 therapy is ...typically based on patient PD-L1 immunohistochemistry (IHC) which has low specificity for predicting disease control. Therefore, there is a critical need for a clinical biomarker that will predict clinical benefit to anti-PD-1 treatment with high specificity.
Methods
Clinical treatment and outcomes data for 103 RM-HNSCC patients were paired with RNA-sequencing data from formalin-fixed patient samples. Using logistic regression methods, we developed a novel biomarker classifier based on expression patterns in the tumor immune microenvironment to predict disease control with monotherapy PD-1 inhibitors (pembrolizumab and nivolumab). The performance of the biomarker was internally validated using out-of-bag methods.
Results
The biomarker significantly predicted disease control (65% in predicted non-progressors vs. 17% in predicted progressors, p < 0.001) and was significantly correlated with overall survival (OS; p = 0.004). In addition, the biomarker outperformed PD-L1 IHC across numerous metrics including sensitivity (0.79 vs 0.64, respectively; p = 0.005) and specificity (0.70 vs 0.61, respectively; p = 0.009).
Conclusion
This novel assay uses tumor immune microenvironment expression data to predict disease control and OS with high sensitivity and specificity in patients with RM-HNSCC treated with anti-PD-1 monotherapy.
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