Receiver position and acceptance of noise, speech understanding, and sound quality ratings

The effect of receiver position in a hearing aid on acceptance of background noise, speech intelligibility, sound quality judgments, and listener preference was measured in adults with normal to mild sloping to moderate to severe sensorineural hearing loss. Participants were fit with open-fit behind-the-ear (BTE) and receiver-in-the-ear (RITE) hearing aids. After a 3-week trial with each device, acceptance of noise levels, speech understanding in quiet and in noise, and sound quality ratings were conducted. At the conclusion of the study, listener preference between the devices was evaluated. Results revealed that receiver position did not significantly affect acceptance of background noise, speech understanding in quiet or in noise, sound quality ratings, or listener preference, indicating that no difference in objective or subjective benefit was observed based on the position of the receiver in a BTE hearing aid

Influence of T Cell Coinhibitory Molecules on CD8+ Recall Responses

T cell co-signaling molecules play an important role in fine-tuning the strength of T cell activation during many types of immune responses, including infection, cancer, transplant rejection, and autoimmunity. Over the last few decades, intense research into these cosignaling molecules has provided rich evidence to suggest that cosignaling molecules may be harnessed for the treatment of immune-related diseases. In particular, coinhibitory molecules such as programmed-death 1, 2B4, BTLA, TIGIT, LAG-3, TIM-3, and CTLA-4 inhibit T cell responses by counteracting TCR and costimulatory signals, leading to the inhibition of proliferation and effector function and the downregulation of activation and adhesion molecules at the cell surface. While many reviews have focused on the role of coinhibitory molecules in modifying primary CD8+ T cell responses, in this review, we will consider the complex role of coinhibitory molecules in altering CD8+ T cell recall potential. As memory CD8+ T cell responses are critical for protective memory responses in infection and cancer and contribute to potentially pathogenic memory responses in transplant rejection and autoimmunity, understanding the role of coinhibitory receptor control of memory T cells may illuminate important aspects of therapeutically targeting these pathways

Low agreement among reviewers evaluating the same NIH grant applications

Obtaining grant funding from the National Institutes of Health (NIH) is increasingly competitive, as funding success rates have declined over the past decade. To allocate relatively scarce funds, scientific peer reviewers must differentiate the very best applications from comparatively weaker ones. Despite the importance of this determination, little research has explored how reviewers assign ratings to the applications they review and whether there is consistency in the reviewers’ evaluation of the same application. Replicating all aspects of the NIH peer-review process, we examined 43 individual reviewers’ ratings and written critiques of the same group of 25 NIH grant applications. Results showed no agreement among reviewers regarding the quality of the applications in either their qualitative or quantitative evaluations. Although all reviewers received the same instructions on how to rate applications and format their written critiques, we also found no agreement in how reviewers “translated” a given number of strengths and weaknesses into a numeric rating. It appeared that the outcome of the grant review depended more on the reviewer to whom the grant was assigned than the research proposed in the grant. This research replicates the NIH peer-review process to examine in detail the qualitative and quantitative judgments of different reviewers examining the same application, and our results have broad relevance for scientific grant peer review

An Approach to the Cosmological Constant Problem(s)

We propose an approach to explaining why naive large quantum fluctuations are not the right estimate for the cosmological constant. We argue that the universe is in a superposition of many vacua, in such a way that the resulting fluctuations are suppressed by level repulsion to a very small value. The approach combines several aspects of string theory and the early history of the universe, and is only valid if several assumptions hold true. The approach may also explain why the effective cosmological constant reamins small as the universe evolves though several phase transitions. It provides a non-anthropic mechansim leading to a small, non-zero cosmological constant.Comment: Talk given at Rencontres de Moriond, 2004 by G.L. Kan

The Luminosity and Energy Dependence of Pulse Phase Lags in the Accretion-Powered Millisecond Pulsar Sax J1808.4-3658

Soft phase lags, in which X-ray pulses in lower energy bands arrive later than pulses in higher energy bands, have been observed in nearly all accretion-powered millisecond pulsars, but their origin remains an open question. In a study of the 2.5 ms accretion-powered pulsar SAX J1808.4–3658, we report that the magnitude of these lags is strongly dependent on the accretion rate. During the brightest stage of the outbursts from this source, the lags increase in magnitude as the accretion rate drops; when the outbursts enter their dimmer flaring-tail stage, the relationship reverses. We evaluate this complex dependence in the context of two theoretical models for the lags, one relying on the scattering of photons by the accretion disk and the other invoking a two-component model for the photon emission. In both cases, the turnover suggests that we are observing the source transitioning into the "propeller" accretion regime.United States. National Aeronautics and Space Administration. RXTE Guest Observer Progra

Different thyroid assays may greatly affect diagnosis and management of hypothyroidism

This is an accepted manuscript of an article published by BMJ Publishing Group in BMJ on 09/06/2021, available online: https://doi.org/10.1136/bmj.n1458 The accepted version of the publication may differ from the final published version.Letter to the editor, replying to Investigating hypothyroidism, Published: 27 April 2021; BMJ 373 doi:10.1136/bmj.n993Published versio

Tortoise or hare? Supporting the chronotype preference of employees with fluctuating chronic illness symptoms

Objective: Our aim is to understand how to facilitate the job retention of employees with chronic illness. We focus on multiple sclerosis (MS) as a criterion chronic illness. Design: An opportunity sample of 20 individuals of working age (13 female; 7 male) were recruited who had been in paid employment for over 28 months with a concurrent diagnosis of MS. Participants took part in one of three focus groups with a topic guide comprising eight keywords: work, coping, performance, support, future, expectations, and sharing symptoms. Data were analysed using dialogical analysis. Main outcome measures: As a qualitative study, no outcome measure was used. However, the specific focus of interest was to search for differential patterns of ‘timespace’ – chronotope - that people with chronic illness utilize to manage their condition in the workplace. Results: Participants oriented to two distinct chronotope types: unsustainable epic (characterized by condensed time) and temporary idyll (characterized by condensed space). Perceived managerial discretion was identified as possibly influencing participants’ chronotope preference. Conclusion: Identifying chronotope preference has practical implications for health psychologists and related professionals who provide and advise on support to facilitate people with chronic illness to thrive in the workplace

Genome Sequence of the Mesophilic Thermotogales Bacterium Mesotoga prima MesG1.Ag.4.2 Reveals the Largest Thermotogales Genome To Date

Here we describe the genome of Mesotoga prima MesG1.Ag4.2, the first genome of a mesophilic Thermotogales bacterium. Mesotoga prima was isolated from a polychlorinated biphenyl (PCB)-dechlorinating enrichment culture from Baltimore Harbor sediments. Its 2.97 Mb genome is considerably larger than any previously sequenced Thermotogales genomes, which range between 1.86 and 2.30 Mb. This larger size is due to both higher numbers of protein-coding genes and larger intergenic regions. In particular, the M. prima genome contains more genes for proteins involved in regulatory functions, for instance those involved in regulation of transcription. Together with its closest relative, Kosmotoga olearia, it also encodes different types of proteins involved in environmental and cell–cell interactions as compared with other Thermotogales bacteria. Amino acid composition analysis of M. prima proteins implies that this lineage has inhabited low-temperature environments for a long time. A large fraction of the M. prima genome has been acquired by lateral gene transfer (LGT): a DarkHorse analysis suggests that 766 (32%) of predicted protein-coding genes have been involved in LGT after Mesotogadiverged from the other Thermotogales lineages. A notable example of a lineage-specific LGT event is a reductive dehalogenase gene—a key enzyme in dehalorespiration, indicating M. prima may have a more active role in PCB dechlorination than was previously assumed

Improving Information on Maternal Medication Use by Linking Prescription Data to Congenital Anomaly Registers: A EUROmediCAT Study

Research on associations between medication use during pregnancy and congenital anomalies is significative for assessing the safe use of a medicine in pregnancy. Congenital anomaly (CA) registries do not have optimal information on medicine exposure, in contrast to prescription databases. Linkage of prescription databases to the CA registries is a potentially effective method of obtaining accurate information on medicine use in pregnancies and the risk of congenital anomalies. We linked data from primary care and prescription databases to five European Surveillance of Congenital Anomalies (EUROCAT) CA registries. The linkage was evaluated by looking at linkage rate, characteristics of linked and non-linked cases, first trimester exposure rates for six groups of medicines according to the prescription data and information on medication use registered in the CA databases, and agreement of exposure. Of the 52,619 cases registered in the CA databases, 26,552 could be linked. The linkage rate varied between registries over time and by type of birth. The first trimester exposure rates and the agreements between the databases varied for the different medicine groups. Information on anti-epileptic drugs and insulins and analogue medicine use recorded by CA registries was of good quality. For selective serotonin reuptake inhibitors, anti-asthmatics, antibacterials for systemic use, and gonadotropins and other ovulation stimulants, the recorded information was less complete. Linkage of primary care or prescription databases to CA registries improved the quality of information on maternal use of medicines in pregnancy, especially for medicine groups that are less fully registered in CA registries

Dysfunctional BMPR2 signaling drives an abnormal endothelial requirement for glutamine in pulmonary arterial hypertension

Pulmonary arterial hypertension (PAH) is increasingly recognized as a systemic disease driven by alteration in the normal functioning of multiple metabolic pathways affecting all of the major carbon substrates, including amino acids. We found that human pulmonary hypertension patients (WHO Group I, PAH) exhibit systemic and pulmonary-specific alterations in glutamine metabolism, with the diseased pulmonary vasculature taking up significantly more glutamine than that of controls. Using cell culture models and transgenic mice expressing PAH-causing BMPR2 mutations, we found that the pulmonary endothelium in PAH shunts significantly more glutamine carbon into the tricarboxylic acid (TCA) cycle than wild-type endothelium. Increased glutamine metabolism through the TCA cycle is required by the endothelium in PAH to survive, to sustain normal energetics, and to manifest the hyperproliferative phenotype characteristic of disease. The strict requirement for glutamine is driven by loss of sirtuin-3 (SIRT3) activity through covalent modification by reactive products of lipid peroxidation. Using 2-hydroxybenzylamine, a scavenger of reactive lipid peroxidation products, we were able to preserve SIRT3 function, to normalize glutamine metabolism, and to prevent the development of PAH in BMPR2 mutant mice. In PAH, targeting glutamine metabolism and the mechanisms that underlie glutamine-driven metabolic reprogramming represent a viable novel avenue for the development of potentially disease-modifying therapeutics that could be rapidly translated to human studies