Post-copulatory opportunities for sperm competition and cryptic female choice provide no offspring fitness benefits in externally fertilizing salmon

There is increasing evidence that females can somehow improve their offspring fitness by mating with multiple males, but we understand little about the exact stage(s) at which such benefits are gained. Here, we measure whether offspring fitness is influenced by mechanisms operating solely between sperm and egg. Using externally-fertilising and polyandrous Atlantic salmon (Salmo salar), we employed split-clutch and split-ejaculate in vitro fertilisation experiments to generate offspring using designs that either denied or applied opportunities for sperm competition and cryptic female choice. Following fertilisations, we measured 140 days of offspring fitness after hatch, through growth and survival in hatchery and near-natural conditions. Despite an average composite mortality of 61%, offspring fitness at every life stage was near-identical between groups fertilised under the absence versus presence of opportunities for sperm competition and cryptic female choice. Of the 21,551 and 21,771 eggs from 24 females fertilised under monandrous versus polyandrous conditions, 68% versus 67.8% survived to the 100-day juvenile stage; sub-samples showed similar hatching success (73.1% versus 74.3%), had similar survival over 40 days in near-natural streams (57.3% versus 56.2%), and grew at similar rates throughout. We therefore found no evidence that gamete-specific interactions allow offspring fitness benefits when polyandrous fertilisation conditions provide opportunities for sperm competition and cryptic female choice

Effective health care for older people resident in care homes: the optimal study protocol for realist review

This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.Background: Care homes in the UK rely on general practice for access to specialist medical and nursing care as well as referral to therapists and secondary care. Service delivery to care homes is highly variable in both quantity and quality. This variability is also evident in the commissioning and organisation of care home-specific services that range from the payment of incentives to general practitioners (GPs) to visit care homes, to the creation of care home specialist teams and outreach services run by geriatricians. No primary studies or systematic reviews have robustly evaluated the impact of these different approaches on organisation and resident-level outcomes. Our aim is to identify factors which may explain the perceived or demonstrated effectiveness of programmes to improve health-related outcomes in older people living in care homes. Methods/Design: A realist review approach will be used to develop a theoretical understanding of what works when, why and in what circumstances. Elements of service models of interest include those that focus on assessment and management of residents’ health, those that use strategies to encourage closer working between visiting health care providers and care home staff, and those that address system-wide issues about access to assessment and treatment. These will include studies on continence, dignity, and speech and language assessment as well as interventions to promote person centred dementia care, improve strength and mobility, and nutrition. The impact of these interventions and their different mechanisms will be considered in relation to five key outcomes: residents’ medication use, use of out of hours’ services, hospital admissions (including use of Accident and Emergency) and length of hospital stay, costs and user satisfaction. An iterative three-stage approach will be undertaken that is stakeholder-driven and optimises the knowledge and networks of the research team. Discussion: This realist review will explore why and for whom different approaches to providing health care to residents in care homes improves access to health care in the five areas of interest. It will inform commissioning decisions and be the basis for further research. This systematic review protocol is registered on the PROSPERO database reference number: CRD42014009112NIHR Health Services & Delivery Research Programme. Project number 11/1021/0

Cryptic choice of conspecific sperm controlled by the impact of ovarian fluid on sperm swimming behavior

Despite evidence that variation in male–female reproductive compatibility exists in many fertilization systems, identifying mechanisms of cryptic female choice at the gamete level has been a challenge. Here, under risks of genetic incompatibility through hybridization, we show how salmon and trout eggs promote fertilization by conspecific sperm. Using in vitro fertilization experiments that replicate the gametic microenvironment, we find complete interfertility between both species. However, if either species’ ova were presented with equivalent numbers of both sperm types, conspecific sperm gained fertilization precedence. Surprisingly, the species’ identity of the eggs did not explain this cryptic female choice, which instead was primarily controlled by conspecific ovarian fluid, a semiviscous, protein-rich solution that bathes the eggs and is released at spawning. Video analyses revealed that ovarian fluid doubled sperm motile life span and straightened swimming trajectory, behaviors allowing chemoattraction up a concentration gradient. To confirm chemoattraction, cell migration tests through membranes containing pores that approximated to the egg micropyle showed that conspecific ovarian fluid attracted many more spermatozoa through the membrane, compared with heterospecific fluid or water. These combined findings together identify how cryptic female choice can evolve at the gamete level and promote reproductive isolation, mediated by a specific chemoattractive influence of ovarian fluid on sperm swimming behavior

What is the contribution of physician associates in hospital care in England? A mixed methods, multiple case study.

OBJECTIVES: To investigate the deployment of physician associates (PAs); the factors supporting and inhibiting their employment and their contribution and impact on patients' experience and outcomes and the organisation of services. DESIGN: Mixed methods within a case study design, using interviews, observations, work diaries and documentary analysis. SETTING: Six acute care hospitals in three regions of England in 2016-2017. PARTICIPANTS: 43 PAs, 77 other health professionals, 28 managers, 28 patients and relatives. RESULTS: A key influencing factor supporting the employment of PAs in all settings was a shortage of doctors. PAs were found to be acceptable, appropriate and safe members of the medical/surgical teams by the majority of doctors, managers and nurses. They were mainly deployed to undertake inpatient ward work in the medical/surgical team during core weekday hours. They were reported to positively contribute to: continuity within their medical/surgical team, patient experience and flow, inducting new junior doctors, supporting the medical/surgical teams' workload, which released doctors for more complex patients and their training. The lack of regulation and attendant lack of authority to prescribe was seen as a problem in many but not all specialties. The contribution of PAs to productivity and patient outcomes was not quantifiable separately from other members of the team and wider service organisation. Patients and relatives described PAs positively but most did not understand who and what a PA was, often mistaking them for doctors. CONCLUSIONS: This study offers new insights concerning the deployment and contribution of PAs in medical and surgical specialties in English hospitals. PAs provided a flexible addition to the secondary care workforce without drawing from existing professions. Their utility in the hospital setting is unlikely to be completely realised without the appropriate level of regulation and authority to prescribe medicines and order ionising radiation within their scope of practice

Local dynamics of gap-junction-coupled interneuron networks

Interneurons coupled by both electrical gap-junctions (GJs) and chemical GABAergic synapses are major components of forebrain networks. However, their contributions to the generation of specific activity patterns, and their overall contributions to network function, remain poorly understood. Here we demonstrate, using computational methods, that the topological properties of interneuron networks can elicit a wide range of activity dynamics, and either prevent or permit local pattern formation. We systematically varied the topology of GJ and inhibitory chemical synapses within simulated networks, by changing connection types from local to random, and changing the total number of connections. As previously observed we found that randomly coupled GJs lead to globally synchronous activity. In contrast, we found that local GJ connectivity may govern the formation of highly spatially heterogeneous activity states. These states are inherently temporally unstable when the input is uniformly random, but can rapidly stabilize when the network detects correlations or asymmetries in the inputs. We show a correspondence between this feature of network activity and experimental observations of transient stabilization of striatal fast-spiking interneurons (FSIs), in electrophysiological recordings from rats performing a simple decision-making task. We suggest that local GJ coupling enables an active search-and-select function of striatal FSIs, which contributes to the overall role of cortical-basal ganglia circuits in decision-making.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/85426/1/ph10_1_016015.pd

17β-Estradiol Potentiates the Reinstatement of Cocaine Seeking in Female Rats: Role of the Prelimbic Prefrontal Cortex and Cannabinoid Type-1 Receptors

Clinical observations imply that female cocaine addicts experience enhanced relapse vulnerability compared with males, an effect tied to elevated estrogen phases of the ovarian hormone cycle. Although estrogens can enhance drug-seeking behavior, they do not directly induce reinstatement on their own. To model this phenomenon, we tested whether an estrogen could augment drug-seeking behavior in response to an ordinarily subthreshold reinstatement trigger. Following cocaine self-administration and extinction, female rats were ovariectomized to isolate estrogen effects on reinstatement. Although neither peak proestrus levels of the primary estrogen 17β-estradiol (E2; 10 μg/kg, i.p., 1-h pretreatment) nor a subthreshold cocaine dose (1.25 mg/kg, i.p.) alone were sufficient to reinstate drug-seeking behavior, pretreatment with E2 potentiated reinstatement to the ordinarily subthreshold cocaine dose. Furthermore, E2 microinfusions revealed that E2 (5 μg/0.3 μl, 15-min pretreatment) acts directly within the prelimbic prefrontal cortex (PrL-PFC) to potentiate reinstatement. As E2 has been implicated in endocannabinoid mobilization, which can disinhibit PrL-PFC projection neurons, we investigated whether cannabinoid type-1 receptor (CB1R) activation is necessary for E2 to potentiate reinstatement. The CB1R antagonist AM251 (1 or 3 mg/kg, i.p., 30-min pretreatment) administered prior to E2 and cocaine suppressed reinstatement in a dose-dependent manner. Finally, PrL-PFC AM251 microinfusions (300 ng/side, 15-min pretreatment) also suppressed E2-potentiated reinstatement. Together, these results suggest that E2 can augment reactivity to an ordinarily subthreshold relapse trigger in a PrL-PFC CB1R activation-dependent manner

Structures and Mechanisms Design Concepts for Adaptive Deployable Entry Placement Technology

System studies have shown that large deployable aerodynamic decelerators such as the Adaptive Deployable Entry and Placement Technology (ADEPT) concept can revolutionize future robotic and human exploration missions involving atmospheric entry, descent and landing by significantly reducing the maximum heating rate, total heat load, and deceleration loads experienced by the spacecraft during entry [1-3]. ADEPT and the Hypersonic Inflatable Aerodynamic Decelerator (HIAD) [4] share the approach of stowing the entry system in the shroud of the launch vehicle and deploying it to a much larger diameter prior to entry. The ADEPT concept provides a low ballistic coefficient for planetary entry by employing an umbrella-like deployable structure consisting of ribs, struts and a fabric cover that form an aerodynamic decelerator capable of undergoing hypersonic flight. The ADEPT "skin" is a 3-D woven carbon cloth that serves as a thermal protection system (TPS) and as a structural surface that transfers aerodynamic forces to the underlying ribs [5]. This paper focuses on design activities associated with integrating ADEPT components (cloth, ribs, struts and mechanisms) into a system that can function across all configurations and environments of a typical mission concept: stowed during launch, in-space deployment, entry, descent, parachute deployment and separation from the landing payload. The baseline structures and mechanisms were selected via trade studies conducted during the summer and fall of 2012. They are now being incorporated into the design of a ground test article (GTA) that will be fabricated in 2013. It will be used to evaluate retention of the stowed configuration in a launch environment, mechanism operation for release, deployment and locking, and static strength of the deployed decelerator. Of particular interest are the carbon cloth interfaces, underlying hot structure, (Advanced Carbon- Carbon ribs) and other structural components (nose cap, struts, and main body) designed to withstand the pressure and extremely high heating experienced during planetary entry

2D and 3D Stem Cell Models of Primate Cortical Development Identify Species-Specific Differences in Progenitor Behavior Contributing to Brain Size.

Variation in cerebral cortex size and complexity is thought to contribute to differences in cognitive ability between humans and other animals. Here we compare cortical progenitor cell output in humans and three nonhuman primates using directed differentiation of pluripotent stem cells (PSCs) in adherent two-dimensional (2D) and organoid three-dimensional (3D) culture systems. Clonal lineage analysis showed that primate cortical progenitors proliferate for a protracted period of time, during which they generate early-born neurons, in contrast to rodents, where this expansion phase largely ceases before neurogenesis begins. The extent of this additional cortical progenitor expansion differs among primates, leading to differences in the number of neurons generated by each progenitor cell. We found that this mechanism for controlling cortical size is regulated cell autonomously in culture, suggesting that primate cerebral cortex size is regulated at least in part at the level of individual cortical progenitor cell clonal output.T.O. was supported by the Wellcome Trust PhD Programme in Developmental Biology at the University of Cambridge. F.J.L. and B.D.S. are Wellcome Trust Investigators. This research was supported by core funding to the Gurdon Institute by the Wellcome Trust and Cancer Research UK. F.H.G. was supported by the Helmsley, Mathers, and JPB Foundations.This is the final version of the article. It first appeared from Elsevier via https://doi.org/10.1016/j.stem.2016.03.00

Physician associates in England's hospitals: a survey of medical directors exploring current usage and factors affecting recruitment.

In the UK secondary care setting, the case for physician associates is based on the cover and stability they might offer to medical teams. We assessed the extent of their adoption and deployment - that is, their current usage and the factors supporting or inhibiting their inclusion in medical teams - using an electronic, self-report survey of medical directors of acute and mental health NHS trusts in England. Physician associates - employed in small numbers, in a range of specialties, in 20 of the responding trusts - were reported to have been employed to fill gaps in medical staffing and support medical specialty trainees. Inhibiting factors were commonly a shortage of physician associates to recruit and lack of authority to prescribe, as well as a lack of evidence and colleague resistance. Our data suggest there is an appetite for employment of physician associates while practical and attitudinal barriers are yet to be fully overcome

Area-preserving dynamics of a long slender finger by curvature: a test case for the globally conserved phase ordering

A long and slender finger can serve as a simple ``test bed'' for different phase ordering models. In this work, the globally-conserved, interface-controlled dynamics of a long finger is investigated, analytically and numerically, in two dimensions. An important limit is considered when the finger dynamics are reducible to the area-preserving motion by curvature. A free boundary problem for the finger shape is formulated. An asymptotic perturbation theory is developed that uses the finger aspect ratio as a small parameter. The leading-order approximation is a modification of ``the Mullins finger" (a well-known analytic solution) which width is allowed to slowly vary with time. This time dependence is described, in the leading order, by an exponential law with the characteristic time proportional to the (constant) finger area. The subleading terms of the asymptotic theory are also calculated. Finally, the finger dynamics is investigated numerically, employing the Ginzburg-Landau equation with a global conservation law. The theory is in a very good agreement with the numerical solution.Comment: 8 pages, 4 figures, Latex; corrected typo