Search

Abstract Background Needle-related distress is a common yet poorly recognised and managed problem among haemodialysis (HD) patients. The aim of this pilot study is to test the feasibility and acceptability of the INJECT Intervention—an innovative psychology-based intervention to empower patients to self-manage needle distress with the support of dialysis nurses. Methods This investigator-initiated, single-arm, non-randomised feasibility study will take place in a large dialysis service in Adelaide, Australia. Participants will include patients aged ≥ 18 years, commencing or already receiving maintenance HD, recruited through dialysis physicians and nursing staff as individuals believed to be at risk of needle distress. They will be screened for inclusion using the Dialysis Fear of Injection Questionnaire (DFIQ) and enrolled into the study if the score is ≥ 2. The multi-pronged intervention encompasses (i) psychologist review, (ii) patient self-management program and (iii) nursing education program. The primary aim is to evaluate feasibility and acceptability of the intervention from patient and dialysis nurse perspectives, including recruitment, retention, engagement with the intervention and completion. Secondary exploratory outcomes will assess suitability of various tools for measuring needle distress, evaluate acceptability of the nursing education program and measure cannulation-related trauma and vascular access outcomes. Conclusion The results will inform the protocol for larger trials addressing needle distress in HD patients. Trial registration Australian New Zealand Clinical Trials Registry (ANZCTR): ACTRN12621000229875, approved 4 April 2021, https://www.anzctr.org.au/ .

The article aims to update the evidence and to diversify the research agenda on leadership roles of women senior-managers. This research work draws attention to the essential gap in the research of women as senior-managers and organizational leaders. In the first place, it notices that while the conceptualization of leadership has expanded to define leadership from interpersonal to organizational influence, the research on women leadership has not updated accordingly. The article claims that research agenda on women in organizations overlooks examination of women as senior-managers and respectively overlooks understanding of the leadership roles that women perform to organizations. Second, the article aims to examine and update the evidence as per the interplay of gender and women senior-managers’ leadership roles in organizational context. Namely, the research examines how women senior-managers perceive their leadership mandate, and whether organizations enable or constrain it. Results of the 21 indepth semi-standardized interviews identified three distinct leadership roles that women senior-managers perceive as requisite for the roles of senior-manager. That is followed by a discussion of implications for organizational leadership theory and organizational routines. Key words: women senior-managers, gender, organizational behavior, leadership roles.

Understanding green turtle habitat use during the nesting season is important for informing management decisions relating to green turtles and ecosystems that support them. Despite patterns such as migration being described, few studies investigate behaviour during the inter-nesting period. This research aims to describe and quantify the spatial distribution patterns of green turtles during 2 nesting seasons on Raine Island in the northern Great Barrier Reef. Satellite telemetry data were used to analyse the inter-nesting movements and patterns of green turtles in 2017 (n = 19) and 2018 (n = 20). The inter-nesting period ranged from 51 to 100 d (76.33 ± 15.98 d) across both seasons. The average inter-nesting area of individual turtles did not differ between nesting seasons (2017: 12.31 ± 13.22 km2, 2018: 12.01 ± 21.92 km2). In addition, it was established that 39 individuals are a sufficient sample size to describe the spatial distribution. Approximately half of the tracked individuals remained at the same reef for their entire inter-nesting season (n = 19), and half used habitat on nearby reefs (n = 20). Most turtles showed fidelity to Raine Island as a nesting site (n = 37), laying all their clutches on the island. However, 2 individuals travelled 479 and 337 km during the inter-nesting period. This study thus highlights where the habitats used by green turtles during the inter-nesting season are and how they are used. Therefore, management strategies and conservation decisions can be informed to maintain the viability of these essential habitats.

Abstract Background In current care, patients’ personal and self-reported family histories are primarily used to determine whether genetic testing for hereditary endocrine tumor syndromes (ETS) is indicated. Population genomic screening for other conditions has increased ascertainment of individuals with pathogenic/likely pathogenic (P/LP) variants, leading to improved management and earlier diagnoses. It is unknown whether such benefits occur when screening broader populations for P/LP ETS variants. This manuscript assesses clinical utility outcomes of a large, unselected, healthcare-based genomic screening program by describing personal and family history of syndrome-related features, risk management behaviors after result disclosure, and rates of relevant post-disclosure diagnoses in patient-participants with P/LP ETS variants. Methods Observational study of individuals informed of a P/LP variant in MEN1, RET, SDHAF2, SDHB, SDHC, SDHD, or VHL through Geisinger’s MyCode Community Health Initiative between June 2016 and October 2019. Electronic health records (EHRs) of participants were evaluated for a report of pre-disclosure personal and self-reported family histories and post-disclosure risk management and diagnoses. Results P/LP variants in genes of interest were identified in 199 of 130,490 (1 in 656) adult Geisinger MyCode patient-participants, 80 of which were disclosed during the study period. Eighty-one percent (n = 65) did not have prior evidence of the result in their EHR and, because they were identified via MyCode, were included in further analyses. Five participants identified via MyCode (8%) had a personal history of syndrome-related features; 16 (25%) had a positive self-reported family history. Time from result disclosure to EHR review was a median of 0.7 years. Post-disclosure, 36 (55.4%) completed a recommended risk management behavior; 11 (17%) were diagnosed with a syndrome-related neoplasm after completing a risk management intervention. Conclusions Broader screening for pathogenic/likely pathogenic variants associated with endocrine tumor syndromes enables detection of at-risk individuals, leads to the uptake of risk management, and facilitates relevant diagnoses. Further research will be necessary to continue to determine the clinical utility of screening diverse, unselected populations for such variants.

Abstract Background Advanced chronic obstructive pulmonary disease (COPD) often leads to hospitalisation and invasive aspergillosis (IA) is a serious complication. Aspergillus sensitisation may worsen symptoms in COPD. Methods We identified published papers between January 2000 and May 2019 with > 50 subjects and GOLD criteria for grade II, III or IV (FEV1/FVC 0.05). Conclusions The prevalence of COPD is much higher than previously estimated. Overall COPD mortality may be higher than estimated and IA probably contributes to many deaths. Improved rapid diagnosis of IA using culture and non-culture based techniques is required in COPD hospital admissions to reduce mortality.

Abstract Background Shoulder arthroscopy is a safe and effective procedure with a low complication rate. Although rare, there are potentially life-threatening risks such as fluid extravasation causing airway compromise. Case presentation We report the case of a 65-year-old female treated with an arthroscopic rotator cuff repair who had significant extravasation of arthroscopic fluid causing severe facial and neck swelling. Overnight intubation was required for respiratory monitoring until the edema had resolved enough to allow safe extubation. Conclusion This case highlights the risk factors and clinical course of a patient with airway compromise caused by extravasation of fluid during shoulder arthroscopy. Although shoulder arthroscopy is a safe procedure, surgeon familiarity with the risk factors for this complication and close monitoring can aid in its identification and allow for appropriate treatment.

Summary: The development of new treatments for heart failure lack animal models that encompass the increasingly heterogeneous disease profile of this patient population. This report provides evidence supporting the hypothesis that Western Diet−fed, aortic-banded Ossabaw swine display an integrated physiological, morphological, and genetic phenotype evocative of cardio-metabolic heart failure. This new preclinical animal model displays a distinctive constellation of findings that are conceivably useful to extending the understanding of how pre-existing cardio-metabolic syndrome can contribute to developing HF. Key Words: cardio-metabolic disease, heart failure, integrative pathophysiology, preclinical model of cardiovascular disease

Magnetic resonance imaging is considered low risk, yet recent studies have raised a concern of potential damage to DNA in peripheral blood leukocytes. This prospective Institutional Review Board-approved study examined potential double-strand DNA damage by analyzing changes in the DNA damage and repair markers γH2AX and 53BP1 in patients who underwent a 1.5 T gadolinium-enhanced cardiac magnetic resonance (MR) exam. Sixty patients were enrolled (median age 55 years, 39 males). Patients with history of malignancy or who were receiving chemotherapy, radiation therapy, or steroids were excluded. MR sequence data were recorded and blood samples obtained immediately before and after MR exposure. An automated immunofluorescence assay quantified γH2AX or 53BP1 foci number in isolated peripheral blood mononuclear cells. Changes in foci number were analyzed using the Wilcoxon signed-rank test. Clinical and MR procedural characteristics were compared between patients who had a >10% increase in γH2AX or 53BP1 foci numbers and patients who did not. The number of γH2AX foci did not significantly change following cardiac MR (median foci per cell pre-MR = 0.11, post-MR = 0.11, p = .90), but the number of 53BP1 foci significantly increased following MR (median foci per cell pre-MR = 0.46, post-MR = 0.54, p = .0140). Clinical and MR characteristics did not differ significantly between patients who had at least a 10% increase in foci per cell and those who did not. We conclude that MR exposure leads to a small (median 25%) increase in 53BP1 foci, however the clinical relevance of this increase is unknown and may be attributable to normal variation instead of MR exposure.

[This corrects the article DOI: 10.1371/journal.pone.0190890.].

Previous studies have used the zebrafish to investigate the biology of lens crystallin proteins and their roles in development and disease. However, little is known about zebrafish α-crystallin promoter function, how it compares to that of mammals, or whether mammalian α-crystallin promoter activity can be assessed using zebrafish embryos. We injected a variety of α-crystallin promoter fragments from each species combined with the coding sequence for green fluorescent protein (GFP) into zebrafish zygotes to determine the resulting spatiotemporal expression patterns in the developing embryo. We also measured mRNA levels and protein abundance for all three zebrafish α-crystallins. Our data showed that mouse and zebrafish αA-crystallin promoters generated similar GFP expression in the lens, but with earlier onset when using mouse promoters. Expression was also found in notochord and skeletal muscle in a smaller percentage of embryos. Mouse αB-crystallin promoter fragments drove GFP expression primarily in zebrafish skeletal muscle, with less common expression in notochord, lens, heart and in extraocular regions of the eye. A short fragment containing only a lens-specific enhancer region increased lens and notochord GFP expression while decreasing muscle expression, suggesting that the influence of mouse promoter control regions carries over into zebrafish embryos. The two paralogous zebrafish αB-crystallin promoters produced subtly different expression profiles, with the aBa promoter driving expression equally in notochord and skeletal muscle while the αBb promoter resulted primarily in skeletal muscle expression. Messenger RNA for zebrafish αA increased between 1 and 2 days post fertilization (dpf), αBa increased between 4 and 5 dpf, but αBb remained at baseline levels through 5 dpf. Parallel reaction monitoring (PRM) mass spectrometry was used to detect αA, aBa, and αBb peptides in digests of zebrafish embryos. In whole embryos, αA-crystallin was first detected by 2 dpf, peaked in abundance by 4–5 dpf, and was localized to the eye. αBa was detected in whole embryo at nearly constant levels from 1–6 dpf, was also localized primarily to the eye, and its abundance in extraocular tissues decreased from 4–7 dpf. In contrast, due to its low abundance, no αBb protein could be detected in whole embryo, or dissected eye and extraocular tissues. Our results show that mammalian α-crystallin promoters can be efficiently screened in zebrafish embryos and that their controlling regions are well conserved. An ontogenetic shift in zebrafish aBa-crystallin promoter activity provides an interesting system for examining the evolution and control of tissue specificity. Future studies that combine these promoter based approaches with the expanding ability to engineer the zebrafish genome via techniques such as CRISPR/Cas9 will allow the manipulation of protein expression to test hypotheses about lens crystallin function and its relation to lens biology and disease.

HER2-directed therapies are less effective in patients with ERpos compared to ERneg breast cancer, possibly reflecting bidirectional activation between HER2 and estrogen signaling pathways. We investigated dual blockade using anti-HER2 vaccination and anti-estrogen therapy in HER2pos/ERpos early breast cancer patients. In pre-clinical studies of HER2pos breast cancer cell lines, ERpos cells were partially resistant to CD4+ Th1 cytokine-induced metabolic suppression compared with ERneg cells. The addition of anti-estrogen treatment significantly enhanced cytokine sensitivity in ERpos, but not ERneg, cell lines. In two pooled phase-I clinical trials, patients with HER2pos early breast cancer were treated with neoadjuvant anti-HER2 dendritic cell vaccination; HER2pos/ERpos patients were treated with or without concurrent anti-estrogen therapy. The anti-HER2 Th1 immune response measured in the peripheral blood significantly increased following vaccination, but was similar across the three treatment groups (ERneg vaccination alone, ERpos vaccination alone, ERpos vaccination + anti-estrogen therapy). In the sentinel lymph nodes, however, the anti-HER2 Th1 immune response was significantly higher in ERpos patients treated with combination anti-HER2 vaccination plus anti-estrogen therapy compared to those treated with anti-HER2 vaccination alone. Similar rates of pathologic complete response (pCR) were observed in vaccinated ERneg patients and vaccinated ERpos patients treated with concurrent anti-estrogen therapy (31.4% vs. 28.6%); both were significantly higher than the pCR rate in vaccinated ERpos patients who did not receive anti-estrogen therapy (4.0%, p = 0.03). Since pCR portends long-term favorable outcomes, these results support additional clinical investigations using HER2-directed vaccines in combination with anti-estrogen treatments for ERpos/HER2pos DCIS and invasive breast cancer.

Food availability is the primary limitation for terrestrial Arctic predators, many of which rely on rodents that fluctuate in abundance over a 3–5-year period. During rodent scarcity, predators such as Arctic foxes (Vulpes lagopus) consume alternative prey, such as migratory birds, which are plentiful during summer. In most of the Arctic these birds return south by August, but in northern Manitoba, near the southern edge of the Arctic fox distribution, large numbers of lesser snow geese (Chen caerulescens caerulescens) and Canada geese (Branta canadensis interior) persist into October. This extended availability of geese late into fall may reduce the dependence of Arctic foxes on rodents. We used stable isotope and faecal analyses to reconstruct the Arctic fox fall and winter diet and related the most probable contributions of lemmings, goose eggs and juvenile geese with changes in prey availability and fox reproduction. Geese were a potentially important component of the fall diet for Arctic foxes, especially in years with high goose productivity, but rodents were the main component of the diet in late winter, even though rodents were scarce each summer (2010–2013). Furthermore, rodent density had a greater influence on Arctic fox reproduction, which was correlated with the subsequent winter harvest, than any other variable examined. Although geese were important fall prey for Arctic foxes at the southern edge of their distribution, they did not buffer declines in availability of rodents, which were the primary prey in April when food availability is critical for Arctic fox reproduction.

BackgroundCyclic guanosine monophosphate‐protein kinase G‐phosphodiesterase 5 signaling may be disturbed in heart failure (HF) with preserved ejection fraction, contributing to cardiac remodeling and dysfunction. The purpose of this study was to manipulate cyclic guanosine monophosphate signaling using the dipeptidyl‐peptidase 4 inhibitor saxagliptin and phosphodiesterase 5 inhibitor tadalafil. We hypothesized that preservation of cyclic guanosine monophosphate cGMP signaling would attenuate pathological cardiac remodeling and improve left ventricular (LV) function. Methods and ResultsWe assessed LV hypertrophy and function at the organ and cellular level in aortic‐banded pigs. Concentric hypertrophy was equal in all groups, but LV collagen deposition was increased in only HF animals. Prevention of fibrotic remodeling by saxagliptin and tadalafil was correlated with neuropeptide Y plasma levels. Saxagliptin better preserved integrated LV systolic and diastolic function by maintaining normal LV chamber volumes and contractility (end‐systolic pressure‐volume relationship, preload recruitable SW) while preventing changes to early/late diastolic longitudinal strain rate. Function was similar to the HF group in tadalafil‐treated animals including increased LV contractility, reduced chamber volume, and decreased longitudinal, circumferential, and radial mechanics. Saxagliptin and tadalafil prevented a negative cardiomyocyte shortening‐frequency relationship observed in HF animals. Saxagliptin increased phosphodiesterase 5 activity while tadalafil increased cyclic guanosine monophosphate levels; however, neither drug increased downstream PKG activity. Early mitochondrial dysfunction, evident as decreased calcium‐retention capacity and Complex II‐dependent respiratory control, was present in both HF and tadalafil‐treated animals. ConclusionsBoth saxagliptin and tadalafil prevented increased LV collagen deposition in a manner related to the attenuation of increased plasma neuropeptide Y levels. Saxagliptin appears superior for treating heart failure with preserved ejection fraction, considering its comprehensive effects on integrated LV systolic and diastolic function.

Background. Hand function is essential to a person’s self-efficacy and greatly affects quality of life. Adapted utensils with handles of increased diameters have historically been used to assist individuals with arthritis or other hand disabilities for feeding, and other related activities of daily living. To date, minimal research has examined the biomechanical effects of modified handles, or quantified the differences in ranges of motion (ROM) when using a standard versus a modified handle. The aim of this study was to quantify the ranges of motion (ROM) required for a healthy hand to use different adaptive spoons with electrogoniometry for the purpose of understanding the physiologic advantages that adapted spoons may provide patients with limited ROM. Methods. Hand measurements included the distal interphalangeal joint (DIP), proximal interphalangeal joint (PIP), and metacarpophalangeal joint (MCP) for each finger and the interphalangeal (IP) and MCP joint for the thumb. Participants were 34 females age 18–30 (mean age 20.38 ± 1.67) with no previous hand injuries or abnormalities. Participants grasped spoons with standard handles, and spoons with handle diameters of 3.18 cm (1.25 inch), and 4.45 cm (1.75 inch). ROM measurements were obtained with an electrogoniometer to record the angle at each joint for each of the spoon handle sizes. Results. A 3 × 3 × 4 repeated measures ANOVA (Spoon handle size by Joint by Finger) found main effects on ROM of Joint (F(2, 33) = 318.68, Partial η2 = .95, p < .001), Spoon handle size (F(2, 33) = 598.73, Partial η2 = .97, p < .001), and Finger (F(3, 32) = 163.83, Partial η2 = .94, p < .001). As the spoon handle diameter size increased, the range of motion utilized to grasp the spoon handle decreased in all joints and all fingers (p < 0.01). Discussion. This study confirms the hypothesis that less range of motion is required to grip utensils with larger diameter handles, which in turn may reduce challenges for patients with limited ROM of the hand.

There is increasing evidence that energy metabolism is disturbed in Amyotrophic Lateral Sclerosis (ALS) patients and animal models. Treatment with triheptanoin, the triglyceride of heptanoate, is a promising approach to provide alternative fuel to improve oxidative phosphorylation and aid ATP generation. Heptanoate can be metabolized to propionyl-CoA, which after carboxylation can produce succinyl-CoA and thereby re-fill the tricarboxylic acid (TCA) cycle (anaplerosis). Here we tested the hypothesis that treatment with triheptanoin prevents motor neuron loss and delays the onset of disease symptoms in female mice overexpressing the mutant human SOD1G93A (hSOD1G93A) gene. When oral triheptanoin (35% of caloric content) was initiated at P35, motor neuron loss at 70 days of age was attenuated by 33%. In untreated hSOD1G93A mice, the loss of hind limb grip strength began at 16.7 weeks. Triheptanoin maintained hind limb grip strength for 2.8 weeks longer (p

Although growing evidence supports an association between allergy, allergens and depression, it remains unknown if this relationship is between “states” (possible triggers) or “traits” (possible vulnerabilities). We hypothesized that patients with recurrent mood disorders who are sensitized to tree pollen (as determined by allergen specific IgE antibodies), in comparison to those who are not sensitized, would report larger negative changes in mood during exposure to tree pollen in spring. We also hypothesized that differences between high and low tree pollen periods in self reported allergy symptoms would correlate positively with differences in self reported depression scores. We present 1-year preliminary data on the first 51 patients with unipolar or bipolar disorder (age: 19-63 years, 65% female, twelve patients were tree-pollen IgE positive). Ratings of mood and allergic disease status were performed once during the peak airborne pollen counts and once during the period of low airborne pollen counts, as reported by two local pollen counting stations. Linear regression models were developed to examine associations of changes in depression scores (dependent variable) with tree pollen sensitization, changes in the allergy symptom severity score, adjusted for gender and order of testing. We did not confirm the hypothesized relationship between a specific tree pollen sensitization and changes in mood during tree pollen exposure. We did confirm the hypothesized positive relationship between the changes in allergy symptoms and changes in subjects' depression scores (adjusted p

Despite rigorous characterization of the role of acetylcholine in retinal development, long-term effects of its absence as a neurotransmitter are unknown. One of the unanswered questions is how acetylcholine contributes to the functional capacity of mature retinal circuits. The current study investigates the effects of disrupting cholinergic signalling in mice, through deletion of vesicular acetylcholine transporter (VAChT) in the developing retina, pigmented epithelium, optic nerve and optic stalk, on electrophysiology and structure of the mature retina.A combination of electroretinography, optical coherence tomography imaging and histological evaluation assessed retinal integrity in mice bearing retina- targeted (embryonic day 12.5) deletion of VAChT (VAChTSix3-Cre-flox/flox) and littermate controls at 5 and 12 months of age. VAChTSix3-Cre-flox/flox mice did not show any gross changes in nuclear layer cellularity or synaptic layer thickness. However, VAChTSix3-Cre-flox/flox mice showed reduced electrophysiological response of the retina to light stimulus under scotopic conditions at 5 and 12 months of age, including reduced a-wave, b-wave, and oscillatory potential (OP) amplitudes and decreased OP peak power and total energy. Reduced a-wave amplitude was proportional to the reduction in b-wave amplitude and not associated with altered a-wave 10%-90% rise time or inner and outer segment thicknesses.This study used a novel genetic model in the first examination of function and structure of the mature mouse retina with disruption of cholinergic signalling. Reduced amplitude across the electroretinogram wave form does not suggest dysfunction in specific retinal cell types and could reflect underlying changes in the retinal and/or extraretinal microenvironment. Our findings suggest that release of acetylcholine by VAChT is essential for the normal electrophysiological response of the mature mouse retina.

We designed a behavioural paradigm for vibro-tactile detection to characterise the sampling time and performance in the rat whisker sensory system. Rats initiated a trial by nose-poking into an aperture where their whiskers came into contact with two meshes. A continuous nose-poke for a random duration triggered stimulus presentation. Stimuli were a sequence of discrete Gaussian deflections of the mesh that increased in amplitude over time - across 5 conditions, time to maximum amplitude varied from 0.5 to 8 seconds. Rats indicated the detected stimulus by choosing between two reward spouts. Two rats completed more than 500 trials per condition. Rats' stimulus sampling duration increased and performance dropped with increasing task difficulty. For all conditions the median reaction time was longer for correct trials than incorrect trials. Higher rates of increment in stimulus amplitude resulted in faster rise in performance as a function of stimulus sampling duration. Rats' behaviour indicated a dynamic stimulus sampling whereby nose-poke was maintained until a stimulus was correctly identified or the rat experienced a false alarm. The perception was then manifested in behaviour after a motor delay. We thus modelled the results with 3 parameters: signal detection, false alarm, and motor delay. The model captured the main features of the data and produced parameter estimates that were biologically plausible and highly similar across the two rats.

In healthy hearts, ventricular ejection is determined by three myofibrillar properties; force, force development rate, and rate of loaded shortening (i.e., power). The sarcomere length and PKA dependence of these mechanical properties were measured in porcine cardiac myocytes. Permeabilized myocytes were prepared from left ventricular free walls and myocyte preparations were calcium activated to yield ~50% maximal force after which isometric force was measured at varied sarcomere lengths. Porcine myocyte preparations exhibited two populations of length-tension relationships, one being shallower than the other. Moreover, myocytes with shallow length-tension relationships displayed steeper relationships following PKA. Sarcomere length-Ktr relationships also were measured and Ktr remained nearly constant over ~2.30 μm to ~1.90 μm and then increased at lengths below 1.90 μm. Loaded-shortening and peak-normalized power output was similar at ~2.30 μm and ~1.90 μm even during activations with the same [Ca2+], implicating a myofibrillar mechanism that sustains myocyte power at lower preloads. PKA increased myocyte power and yielded greater shortening-induced cooperative deactivation in myocytes, which likely provides a myofibrillar mechanism to assist ventricular relaxation. Overall, the bimodal distribution of myocyte length-tension relationships and the PKA-mediated changes in myocyte length-tension and power are likely important modulators of Frank-Starling relationships in mammalian hearts.

The relation between the body mass indices (BMIs) of commercial truck drivers and their involvement in fatigued-driving episodes and safety-critical events is explored in this study. Vehicle motion data and [...]

This study explores the question of reproductive termination (loss of reproductive ability) in female Japanese macaques (Macaca fuscata) from the Arashiyama West (Texas) troop. We used a large sample of completed lives to identify reproductively terminated female Japanese macaques and to consider reproductive termination in Japanese macaques from a comparative life history perspective, which permits meaningful comparisons to be made with human female menopause. We classified a female as reproductively terminated if the time lag between last parturition and death exceeded two standard deviations of the female's own mean lifetime interbirth interval (Caro et al. [1995] Int. J. Primatol. 16:205-220). Seventy of the 95 females in the sample had at least 3 infants over their lifetime (the minimum required for the calculation of a mean and standard deviation), and thus were included in the analysis. Of these 70 females, 20 showed reproductive termination. Reproductively terminated females ranged in age from 14.5-32.7 years, although in females under age 25, reproductive termination was unlikely. The majority of females up to age 25 showed continued parturition. However, after age 25, reproductive termination was population-wide. Length of postreproductive life for reproductively terminated females varied from 0.07-4.4 years, with a mean of 2.08 years. Variation in length of postreproductive life was not related to the age at death of the female. While the occurrence of population-wide reproductive termination after 25 years does suggest similarities with human female menopause, the age at which this termination occurs is very late in the life span, and it was experienced by only 2.9% of the population. Female Japanese monkeys over age 25 are visibly aged and show outward signs of weakness and deterioration, quite unlike the healthy middle age of menopausal human females. Accordingly, as a life history characteristic, reproductive termination in Japanese macaques does not appear to coincide with menopause as experienced by human females. KEY WORDS: menopause; Macaca fuscata; life history; age and reproduction; reproductive senescence; reproductive termination

We report, for the first time, exact analytical boundary solitonsof a generalized cubic-quintic nonlinear Helmholtz (NLH) equation. These solutions have a linked-plateau topology that is distinct from conventional dark soliton solutions; their amplitude and intensity distributions are spatially delocalized and connect regions of finite and zerowave-field disturbances (suggesting also the classification as 'edge solitons'). Extensive numerical simulations compare the stability properties of recently derived Helmholtz bright solitons, for this type of polynomial nonlinearity, to those of the new boundary solitons. The latter are found to possess a remarkable stability characteristic, exhibiting robustness against perturbations that would otherwise lead to the destabilizing of their bright-soliton counterparts. [ABSTRACT FROM AUTHOR]

Background: The implementation of the European working time directive has led to an increase in cross-speciality out-of-hours cover. This survey illustrates ENT out-of-hours cover arrangements and assesses the implications for senior house officers (SHOs) responsible for managing emergencies.Methods: A telephone survey of 100 ENT departments was conducted, asking the on-call SHO about departmental structure, on-call rota design, their previous ENT experience, access to SHO training and their confidence in managing emergencies.Results: 44 per cent of departments used only ENT SHOs on the on-call rota. 73 per cent always had an ENT middle grade on call. In 60 per cent of hospitals, the ENT consultant was sometimes on call with only a non-ENT SHO. At the time of the study, 5 per cent of SHOs had no ENT experience, no access to training, were not confident in managing simple emergencies and were on-call without middle-grade cover.Conclusion: The current junior on-call structure for ENT has implications for patient management. [ABSTRACT FROM AUTHOR]

The nature of work, organizations, and careers has evolved significantly in the past decade. In the wake of these changes, career-development research and implementation have languished. This article addresses this dearth of discourse and practice from the perspective of human resource development (HRD). The authors suggest a framework for reintegrating career development into the HRD function and offer specific learning activities better suited to the needs of individuals and organizations in this turbulent environment. Recommendations for future action are provided. [ABSTRACT FROM AUTHOR]

Recent in vitro studies have shown that acetylcholine (ACh) selectively reduces the efficacy of lateral cortical connections via a muscarinic mechanism, while boosting the efficacy of thalamocortical/feed-forward connections via a nicotinic mechanism. This suggests that high levels of ACh should reduce center-surround interactions of neurons in primary visual cortex, making cells more reliant on feed-forward information. In line with this hypothesis, we show that local iontophoretic application of ACh in primate primary visual cortex reduced the extent of spatial integration, assessed by recording a neurons' length tuning. When ACh was externally applied, neurons' preferred length shifted toward shorter bars, showing reduced impact of the extra-classical receptive field. We fitted a difference and a ratio of Gaussian model to these data to determine the underlying mechanisms of this dynamic change of spatial integration. These models assume overlapping summation and suppression areas with different widths and gains to be responsible for spatial integration and size tuning. ACh significantly reduced the extent of the summation area, but had no significant effect on the extent of the suppression area. In line with previous studies, we also show that applying ACh enhanced the response in the majority of cells, especially in the later (sustained) part of the response. These findings are similar to effects of attention on neuronal activity. The natural release of ACh is strongly linked with states of arousal and attention. Our results may therefore be relevant to the neurobiological mechanism of attention. [ABSTRACT FROM AUTHOR]

During contraction, activation of Ca2+/calmodulin–dependent myosin light chain kinase (MLCK) results in phosphorylation of myosin's regulatory light chain (RLC), which potentiates force and increases speed of force development over a wide range of [Ca2+]. We tested the hypothesis that RLC phosphorylation by MLCK mediates the extent of eccentric contraction–induced injury as measured by force deficit in skinned fast-twitch skeletal muscle fibers. Results indicated that RLC phosphorylation in single skinned rat psoas fibers significantly increased Ca2+ sensitivity of isometric force; isometric force from 50 ± 16 to 59 ± 18 kN/m2 during maximal Ca2+ activation; peak absolute power output from 38 ± 15 to 48 ± 14 nW during maximal Ca2+ activation; and the magnitude of contraction-induced force deficit during maximal (pCa 4.5) activation from 26 ± 9.8 to 35 ± 9.6%. We conclude that RLC phosphorylation increases force deficits following eccentric contractions, perhaps by increasing the number of force-generating cross-bridges. Muscle Nerve 29: 313–317, 2004 [ABSTRACT FROM AUTHOR]

This qualitative exploratory study investigated the career development experiences, concerns, and interests of hourly employees. The study, conducted in the USA, focused on satisfaction with work and careers and the potential role of career development activities in enhancing work life. Results revealed a range of needs and perspectives regarding career development and reinforced the importance of conducting further studies with this key population. While workplace research typically has highlighted managers and executives, hourly employees are essential to organizational output. Therefore organizations are urged to devote more attention to the career development of these often-overlooked employees. [ABSTRACT FROM AUTHOR]

Abstract Nacelle‐mounted, forward‐facing light detection and ranging (LIDAR) technology can deliver benefits to rotor speed regulation and loading reductions of floating offshore wind turbines (FOWTs) when assisting with blade pitch control in above‐rated wind speed conditions. Large‐scale wind turbines may be subject to significant variations in structural loads due to differences in the wind profile across the rotor‐swept area. These loading fluctuations can be mitigated by individual pitch control (IPC). This paper presents a novel LIDAR‐assisted feedforward IPC approach that uses each blade's rotor azimuth position to allocate an individual pitch command from a multi‐beam LIDAR. In this study, the source code of OpenFAST wind turbine modelling software was modified to enable LIDAR simulation and LIDAR‐assisted control. The LIDAR simulation modifications were accepted by the National Renewable Energy Laboratory (NREL) and are now present within OpenFAST releases from v3.5 onwards. Simulations of a 15 MW FOWT were performed across the above‐rated wind spectrum. Under a turbulent wind field with an average wind speed of 17 ms−1, the LIDAR‐assisted feedforward IPC delivered up to 54% reductions in the root mean squared errors and standard deviations of key FOWT parameters. Feedforward IPC delivered enhancements of up to 12% over feedforward collective pitch control, relative to the baseline feedback controller. The reductions to the standard deviation and range of the rotor speed may enable structural optimization of the tower, while the reductions in the variations of the loadings present an opportunity for reduced fatigue damage on turbine components and, consequently, a reduction in maintenance expenditure.

Extravasation of iodinated contrast material (ICM) is an uncommon complication (0.1%-1.2%) following intravenous injection for computed tomography exams and other procedures. Most cases of contrast extravasation are mild and resolve without treatment. Alternative injections sites are occasionally necessary among patients with difficult vascular access and are at increased risk of contrast extravasation and subsequent complications compared to the antecubital fossa. We describe a rare case of airway compromise necessitating intubation following iodinated contrast extravasation from an external jugular IV line. Additional care and monitoring must be performed during and after injection of contrast into these higher-risk vascular access sites.

Abstract Duchenne muscular dystrophy (DMD) is an X‐linked recessive myopathy due to mutations in the dystrophin gene. Diaphragmatic weakness in DMD causes hypoventilation and elevated afterload on the right ventricle (RV). Thus, RV dysfunction in DMD develops early in disease progression. Herein, we deliver a 30‐min sustained RV preload/afterload challenge to isolated hearts of wild‐type (Wt) and dystrophic (Dmdmdx‐4Cv) mice at both young (2–6 month) and middle‐age (8–12 month) to test the hypothesis that the dystrophic RV is susceptible to dysfunction with elevated load. Young dystrophic hearts exhibited greater pressure development than wild type under baseline (Langendorff) conditions, but following RV challenge exhibited similar contractile function as wild type. Following the RV challenge, young dystrophic hearts had an increased incidence of premature ventricular contractions (PVCs) compared to wild type. Hearts of middle‐aged wild‐type and dystrophic mice had similar contractile function during baseline conditions. After RV challenge, hearts of middle‐aged dystrophic mice had severe RV dysfunction and arrhythmias, including ventricular tachycardia. Following the RV load challenge, dystrophic hearts had greater lactate dehydrogenase (LDH) release than wild‐type mice indicative of damage. Our data indicate age‐dependent changes in RV function with load in dystrophin deficiency, highlighting the need to avoid sustained RV load to forestall dysfunction and arrhythmia.

Abstract Background Impairments in social cognition are common after traumatic brain injury (TBI) and may have severe negative consequences for patients and their families. Most tests of social cognition have limited ecological validity due to simplistic and contrived social stimuli with limited relevance to everyday social functioning. There is a need for measures of social cognition that reflect the dynamic, multimodal and contextualized nature of social situations and that predict real-world functioning. Three hundred sixty–degree (360°) Virtual Reality (VR) video can increase ecological validity through enhanced social presence, or a sense of “being there”. This paper describes the development and protocol design for validation of a Norwegian VR-version of The Awareness of Social Inference Test (TASIT), which is a widely used video-based test of social cognition. Methods Development of VR TASIT included filming 61 short videos depicting social interactions in both VR and desktop format, using a 360° camera. Software for standardized test administration and collection of performance data was developed in Unity, for administration on both VR and desktop interface. The validation study will test the reliability and validity of VR TASIT in participants with TBI (n = 100) and healthy controls (n = 100). Half of the participants will perform the desktop version, and the other half the VR version. Analyses will include known groups validity, convergent and divergent validity, as well as test–retest reliability of VR TASIT. A comparison of the ability of TASIT VR and desktop versions to predict real-world functioning (ecological validity) will be explored using the Social Skills Questionnaire for TBI and La Trobe Communication Questionnaire. Finally, the levels of perceived social presence of the stimulus materials and prevalence of cybersickness after exposure to the virtual environment will be documented. Discussion It is expected that VR TASIT will have comparable or better psychometric properties than the desktop version, and that the hypothesized increased level of social presence experienced in a virtual environment will result in improved ecological validity. More broadly, benefits and limitations of using VR video as stimulus material in assessment of social cognition and considerations for future development and clinical validation are discussed. Trial registration The study protocol was pre-registered in ClinicalTrials (April 4th 2022, NCT05309005). The study was retrospectively registered in Open Science Framework (December 15th 2022, osf.io/2vem8).

Understanding insect dispersal helps us predict the spread of insect pests and their natural enemies. Dispersal can be studied by marking, releasing, and recapturing insects, known as mark–release–recapture (MRR). MRR techniques should be convenient, economical, and persistent. Currently, there are limited options for marking small parasitoids that do not impact their fitness and dispersal ability. We evaluated commercially available fluorescent markers used in forensics. These fluorophores can easily be detected by ultraviolet (UV) light, requiring minimal costs and labor to process the marked specimens. This fluorophore marking technique was evaluated with the pest Drosophila suzukii and three parasitoids: Trissolcus japonicus, Pachycrepoideus vindemiae, Ganaspis brasiliensis (=G. kimorum). We evaluated the persistence of the marks on all the insects over time and examined the parasitoids for impacts on longevity, parasitism, locomotor activity, and flight take-off. The green fluorophore marker persisted for over 20 days on all four species. Marking generally did not consistently reduce the survival, parasitism rate, locomotor activity, or take-off of the parasitoids tested. Marked T. japonicus were recaptured in the field up to 100 m away from the release point and three weeks after release, indicating that this technique is a viable method for studying parasitoid dispersal.

Chitalia, Miliotis et al. evaluate radiomic predictors of outcome in patients with breast cancer treated with neoadjuvant chemotherapy. The authors identify radiomic phenotypes related to changes in tumor heterogeneity that improve progression-free survival prediction when added to clinicopathological and molecular factors.

Abstract Breast cancer is one of the most pervasive forms of cancer and its inherent intra- and inter-tumor heterogeneity contributes towards its poor prognosis. Multiple studies have reported results from either private institutional data or publicly available datasets. However, current public datasets are limited in terms of having consistency in: a) data quality, b) quality of expert annotation of pathology, and c) availability of baseline results from computational algorithms. To address these limitations, here we propose the enhancement of the I-SPY1 data collection, with uniformly curated data, tumor annotations, and quantitative imaging features. Specifically, the proposed dataset includes a) uniformly processed scans that are harmonized to match intensity and spatial characteristics, facilitating immediate use in computational studies, b) computationally-generated and manually-revised expert annotations of tumor regions, as well as c) a comprehensive set of quantitative imaging (also known as radiomic) features corresponding to the tumor regions. This collection describes our contribution towards repeatable, reproducible, and comparative quantitative studies leading to new predictive, prognostic, and diagnostic assessments.

Dystrophic cardiomyopathy arises from mutations in the dystrophin gene. Dystrophin forms part of the dystrophin glycoprotein complex and is postulated to act as a membrane stabilizer, protecting the sarcolemma from contraction-induced damage. Duchenne muscular dystrophy (DMD) is the most severe dystrophinopathy, caused by a total absence of dystrophin. Patients with DMD present with progressive skeletal muscle weakness and, because of treatment advances, a cardiac component of the disease (i.e., dystrophic cardiomyopathy) has been unmasked later in disease progression. The role that myofilaments play in dystrophic cardiomyopathy is largely unknown and, as such, this study aimed to address cardiac myofilament function in a mouse model of muscular dystrophy. To assess the effects of DMD on myofilament function, isolated permeabilized cardiomyocytes of wild-type (WT) littermates and Dmdmdx-4cv mice were attached between a force transducer and motor and subjected to contractile assays. Maximal tension and rates of force development (indexed by the rate constant, ktr) were similar between WT and Dmdmdx-4cv cardiac myocyte preparations. Interestingly, Dmdmdx-4cv cardiac myocytes exhibited greater sarcomere length dependence of peak power output compared to WT myocyte preparations. These results suggest dystrophin mitigates length dependence of activation and, in the absence of dystrophin, augmented sarcomere length dependence of myocyte contractility may accelerate ventricular myocyte contraction-induced damage and contribute to dystrophic cardiomyopathy. Next, we assessed if mavacamten, a small molecule modulator of thick filament activation, would mitigate contractile properties observed in Dmdmdx-4cv permeabilized cardiac myocyte preparations. Mavacamten decreased maximal tension and ktr in both WT and Dmdmdx-4cv cardiac myocytes, while also normalizing the length dependence of peak power between WT and Dmdmdx-4cv cardiac myocyte preparations. These results highlight potential benefits of mavacamten (i.e., reduced contractility while maintaining exquisite sarcomere length dependence of power output) as a treatment for dystrophic cardiomyopathy associated with DMD.

Aim: To assess outcomes of Peritoneal Dialysis (PD) in Indigenous (IP) and Non-Indigenous (Non-IP) patients the Top End. Method: Prospective analysis using POET™ database of all patients between 1.1.1993 and 30.11.1999. Results: Results for technique survival and infectious complications are shown in tables 1 and 2. [ABSTRACT FROM AUTHOR]