Patterning of Paternal Investment in Response to Socioecological Change

Human paternal investment, and that of many other species, is facultatively expressed and dependent on a diverse array of individual, social, and ecological conditions. Well-documented are the various ways in which men invest in offspring and the household. Specifically, local ecology structures pay-offs to male investment and has been shown to be an important predictor of the sexual division of labor. However, while variability in paternal investment has been well-characterized cross-culturally, plasticity within a group in response to changing socioecological conditions remains largely unstudied. To address this, we use recent economic development and market access to explore how changes in socioecology alter behavioral options for men and their resultant investment decisions. Among the monogamous Maya, we find that, associated with the introduction of novel subsistence opportunities and incentives for intensified paternal investment, fathers spend more time in the household, more time in domestic activities and more time interacting with their children. The changes in paternal investment documented here are largely contingent on four conditions: increased efficiency in subsistence brought about by mechanized farming, limited opportunities to engage in wage labor, increased opportunities to invest in offspring quality, and a monogamous mating system. Thus, Maya fathers appear to repurpose found time by furthering investment in their families

Chk1 kinase negatively regulates mitotic function of Cdc25A phosphatase through 14-3-3 binding

The order and fidelity of cell cycle events in mammals is intimately linked to the integrity of the Chk1 kinase-Cdc25A phosphatase pathway. Chk1 phosphorylation targets Cdc25A for destruction and, as shown here, inhibits interactions between Cdc25A and its mitotic substrate cyclin B1-Cdk1. Phosphorylation of Cdc25A on serine 178 and threonine 507 facilitates 14-3-3 binding, and Chk1 phosphorylates both residues in vitro. Mutation of T507 to alanine (T507A) enhanced the biological activity of Cdc25A. Cdc25A(T507A) was more efficient in binding to cyclin B1, activating cyclin B1-Cdk1, and promoting premature entry into mitosis. We propose that the Chk1/Cdc25A/14-3-3 pathway functions to prevent cells from entering into mitosis prior to replicating their genomes to ensure the fidelity of the cell division process

Diagnostic accuracy of the Ottawa ankle rule to exclude fractures in acute ankle injuries in adults: a systematic review and meta-analysis

BACKGROUND: Ankle traumas are common presenting injuries to emergency departments in Australia and worldwide. The Ottawa Ankle Rules (OAR) are a clinical decision tool to exclude ankle fractures, thereby precluding the need for radiographic imaging in patients with acute ankle injury. Previous studies support the OAR as an accurate means of excluding ankle and midfoot fractures, but have included a paediatric population, report both the ankle and mid-foot, or are greater than 5 years old. This systematic review and meta-analysis aimed to update and assess the existing evidence of the diagnostic accuracy of the Ottawa Ankle Rule (OAR) acute ankle injuries in adults. METHODS: A systematic search and screen of was performed for relevant articles dated 1992 to 2020. Prospective and retrospective studies documenting OAR outcomes by physicians to assess ankle injuries were included. Critical appraisal of included studies was assessed using the Quality Assessment of Diagnostic Accuracy Studies 2 (QUADAS-2) tool. Outcomes related to psychometric data were pooled using random effects or fixed effects modelling to calculate diagnostic performance of the OAR. Between-study heterogeneity was assessed using the Higgins I2 test, with Spearman’s correlation test for threshold effect. RESULTS: From 254 unique studies identified in the screening process, 15 were included, involving 8560 patients from 13 countries. Sensitivity, specificity, negative likelihood ratio, positive likelihood ratio and diagnostic odds ratio were 0.91 (95% CI, 0.89 to 0.92), 0.25 (95% CI, 0.24 to 0.26), 1.47 (95% CI, 1.11 to 1.93), 0.15 (95% CI, 0.72 to 0.29) and 10.95 (95% CI, 5.14 to 23.35) respectively, with high between-study heterogeneity observed (sensitivity: I2 = 94.3%, p < 0.01; specificity: I2 = 99.2%, p < 0.01). Most studies presented with low risk of bias and concern regarding applicability following assessment against QUADAS-2 criteria. CONCLUSIONS: Application of the OAR is highly sensitive and can correctly predict the likelihood of ankle fractures when present, however, lower specificity rates increase the likelihood of false positives. Overall, the use of the OAR tool is supported as a cost-effective method of reducing unnecessary radiographic referral, that should improve efficiency, lower medical costs and reduce waiting times. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12891-022-05831-7

Untimely illness:When diagnosis does not match age-related expectations

Background We explore the concept of “untimely diagnosis,” where the onset of a long-term condition occurs at a life stage which does not conform to traditional expectations, focusing on two conditions (asthma and arthritis) typically associated with a particular life stage (childhood and older adulthood, respectively). Previous literature has focused on the meaning of chronic illness in terms of life history, and the biographical lens has been used in various ways to make sense of the experience. Less attention has been paid to the condition onset when it seems dissonant with chronological age. Methods Secondary analysis of two qualitative data sets (total 58 interviews) exploring the experiences of people with adult-onset asthma and young people diagnosed with arthritis. Data from the original interview transcripts relating to diagnosis and symptom recognition were re-analysed using a “candidacy” framework to examine how age and diagnosis intersect. Results People did not always assert their candidacy for either condition because of pre-conceived expectations around age. Similarly, health professionals sometimes failed to recognize patients’ candidacy, instead pursuing “age-plausible” possibilities. In some cases, participants were proactive in suggesting a diagnosis to the health professional where diagnosis was delayed. Conclusion The diagnosis of adult-onset asthma, and arthritis in young people, may be regarded as “untimely.” We suggest that being diagnosed with what is perceived to be a “childhood” condition in adulthood, or “an older person's” condition in childhood, may be viewed as a “biographical paradox” and an “untimely breach” to the expected order

Adequacy of clinical information in X-ray referrals for traumatic ankle injury with reference to the Ottawa Ankle Rules-a retrospective clinical audit

Study Objective To assess the adequacy of clinical information with reference to the Ottawa Ankle Rules (OAR) in X-ray referrals for adults with traumatic ankle injury in the ED of a South Australian tertiary hospital and report upon referring trends between emergency department clinicians. Methods A retrospective clinical audit of adult ankle X-ray referrals in the emergency department was conducted. Eligible referrals were screened for their adherence to the OAR, patient details, clinical history and referrer. A logistic regression was used to determine the influence of these factors on the likelihood of being referred for X-rays despite not meeting the OAR criteria. Sensitivity, specificity, positive and negative likelihood ratios and their associated confidence intervals were calculated to assess the diagnostic accuracy of the OAR for those referred. Results Out of the 262 eligible referrals, 163 were deemed to have met the criteria for the OAR. Physiotherapists showed the highest OAR compliance of 77.3% and were the most accurate in their use of the rules, with a sensitivity of 0.86. Medical officers, registrars and interns were 2.5 times more likely to still refer a patient for X-ray if they did not meet the OAR criteria, compared to physiotherapists as the baseline. Patient age, duration of injury etc. were not significantly associated with likelihood of referral (even when they did not meet OAR criteria). The overall sensitivity, specificity, positive and negative likelihood ratios of the OAR were 0.59 (95% CI [0.47–0.71]), 0.37 (95% CI [0.30–0.44]), 0.93 (95% CI [0.76–1.16]) and 1.10 (95% CI [0.82–1.48]) respectively. Conclusion The results of this audit demonstrated poor sensitivity and moderate compliance by referrers with the rule. Reasonable evidence exists for the implementation of individual and/or institutional-based change strategies to improve clinician compliance and accuracy with use of the OAR

Design and Development of Liquid Drug Reservoirs for Microneedle Delivery of Poorly Soluble Drug Molecules

The poor aqueous solubility of existing and emerging drugs is a major issue faced by the pharmaceutical industry. Water-miscible organic solvents, termed co-solvents, can be used to enhance the solubility of poorly soluble substances. Typically, drugs with poor aqueous solubility and Log P &gt; 3 are not amenable to delivery across the skin. This study investigated the use of co-solvents as reservoirs to be used in combination with hydrogel-forming microneedles to enhance the transdermal delivery of hydrophobic compounds, namely Nile red, olanzapine and atorvastatin. A custom-made Franz cell apparatus was fabricated to test the suitability of a liquid drug reservoir in combination with polymeric microneedles. A co-solvency approach to reservoir formulation proved effective, with 83.30% &plusmn; 9.38% of Nile red dye, dissolved in 1 mL poly(ethylene glycol) (PEG 400), permeating neonatal porcine skin over 24 h. PEG 400 and propylene glycol were found to be suitable reservoir media for olanzapine and atorvastatin, with approximately 50% of each drug delivered after 24 h. This work provides crucial proof-of-concept evidence that the manipulation of microneedle reservoir properties is an effective method to facilitate microneedle-mediated delivery of hydrophobic compounds

Tumour occurrence in women with Turner syndrome: a narrative review and single-centre case series

Background: Population studies suggest cancer morbidity may be different in Turner syndrome (TS) compared to the background female population. However, significant variability is observed in cancer associations likely due to heterogeneity in patient cohorts. We explored the prevalence and patterns of cancer amongst a cohort of women with TS attending a dedicated TS clinic. Methods: Retrospective analysis of the patient database was performed to identify TS women who developed cancer. Population data (available before 2015) from the National Cancer Registration and Analysis Service database were used for comparison. Results: Out of 156 TS women, median age of 32 (range 18–73) years, 9 (5.8%) had a recorded cancer diagnosis. Types of cancers were, bilateral gonadoblastoma, type 1 gastric neuroendocrine tumour (NET), appendiceal-NET, gastrointestinal stromal tumour, plasma cell dyscrasia, synovial sarcoma, cervical cancer, medulloblastoma and aplastic anaemia. Median age at cancer diagnosis was 35 (range 7–58) years and two were detected incidentally. Five women had 45,X karyotype, three received growth hormone treatment and all except one received oestrogen replacement therapy. The cancer prevalence of the background age-matched female population was 4.4%. Conclusions: We confirm the previous observations that women with TS do not appear to be at overall increased risk of common malignancies. Our small cohort showed a spectrum of rare malignancies that are not typically associated with TS, except for a single patient with a gonadoblastoma. The slightly higher prevalence of cancer in our cohort might simply represent increased cancer prevalence in the background population, or might be related to small sample size and regular monitoring of these women due to TS per se

Cybersecurity, Image-Based Control, and Process Design and Instrumentation Selection

Within an Industry 4.0 framework, a variety of new considerations are of increasing importance, such as securing processes against cyberattacks on the control systems or utilizing advances in image processing for image-based control. These new technologies impact relationships between process design and control. In this work, we discuss some of these potential relationships, beginning with a discussion of side channel attacks and what they suggest about ways of evaluating plant design and instrumentation selection, along with controller and security schemes, particularly as more data is collected and there is a move toward an industrial Internet of Things. Next, we highlight how the 3D computer graphics software tool set Blender can be utilized to analyze a variety of considerations related to ensuring safety of plant operation and facilitating the design of assemblies with image-based sensing

Daily changes in phytoplankton lipidomes reveal mechanisms of energy storage in the open ocean

© The Author(s), 2018. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in Nature Communications 9 (2018): 5179, doi:10.1038/s41467-018-07346-z.Sunlight is the dominant control on phytoplankton biosynthetic activity, and darkness deprives them of their primary external energy source. Changes in the biochemical composition of phytoplankton communities over diel light cycles and attendant consequences for carbon and energy flux in environments remain poorly elucidated. Here we use lipidomic data from the North Pacific subtropical gyre to show that biosynthesis of energy-rich triacylglycerols (TAGs) by eukaryotic nanophytoplankton during the day and their subsequent consumption at night drives a large and previously uncharacterized daily carbon cycle. Diel oscillations in TAG concentration comprise 23 ± 11% of primary production by eukaryotic nanophytoplankton representing a global flux of about 2.4 Pg C yr−1. Metatranscriptomic analyses of genes required for TAG biosynthesis indicate that haptophytes and dinoflagellates are active members in TAG production. Estimates suggest that these organisms could contain as much as 40% more calories at sunset than at sunrise due to TAG production.This work was supported by a grant from the Simons Foundation, and is a contribution of the Simons Collaboration on Ocean Processes and Ecology (SCOPE award # 329108, B.A.S.V.M.). K.W.B. was further supported by the Postdoctoral Scholarship Program at Woods Hole Oceanographic Institution & U.S. Geological Survey

A Phase II Basket Trial of Dual Anti-CTLA-4 and Anti-PD-1 Blockade in Rare Tumors (DART SWOG 1609) in Patients with Nonpancreatic Neuroendocrine Tumors.

PurposeImmune checkpoint blockade has improved outcomes across tumor types; little is known about the efficacy of these agents in rare tumors. We report the results of the (nonpancreatic) neuroendocrine neoplasm cohort of SWOG S1609 dual anti-CTLA-4 and anti-PD-1 blockade in rare tumors (DART).Patients and methodsWe performed a prospective, open-label, multicenter phase II clinical trial of ipilimumab plus nivolumab across multiple rare tumor cohorts, with the (nonpancreatic) neuroendocrine cohort reported here. Response assessment by grade was not prespecified. The primary endpoint was overall response rate [ORR; RECIST v1.1; complete response (CR) and partial response (PR)]; secondary endpoints included progression-free survival (PFS), overall survival (OS), stable disease &gt;6 months, and toxicity.ResultsThirty-two eligible patients received therapy; 18 (56%) had high-grade disease. Most common primary sites were gastrointestinal (47%; N = 15) and lung (19%; N = 6). The overall ORR was 25% [95% confidence interval (CI) 13-64%; CR, 3%, N = 1; PR, 22%, N = 7]. Patients with high-grade neuroendocrine carcinoma had an ORR of 44% (8/18 patients) versus 0% in low/intermediate grade tumors (0/14 patients; P = 0.004). The 6-month PFS was 31% (95% CI, 19%-52%); median OS was 11 months (95% CI, 6-∞). The most common toxicities were hypothyroidism (31%), fatigue (28%), and nausea (28%), with alanine aminotransferase elevation (9%) as the most common grade 3/4 immune-related adverse event, and no grade 5 events.ConclusionsIpilimumab plus nivolumab demonstrated a 44% ORR in patients with nonpancreatic high-grade neuroendocrine carcinoma, with 0% ORR in low/intermediate grade disease