Notes

(Not really) minding the gap: A qualitative meeting examine of how sociable class tendency may influence youth helping relationships.
elf (self-relevant learning). We found that human participants performed better during prosocial learning than during self-relevant learning, as they were more sensitive toward the information they collected when making choices for the other. Prosocial learning recruited similar brain areas as self-relevant learning, but additionally involved parts of the "social brain" that underpin perspective-taking and self-other distinction. #link# Our findings suggest that people show an inherent tendency toward "intuitive" prosociality.Although the decisions of our daily lives often occur in the context of temporal and reward structures, the impact of such regularities on decision-making strategy is poorly understood. Here, to explore how temporal and reward context modulate strategy, we trained 2 male rhesus monkeys to perform a novel perceptual decision-making task with asymmetric rewards and time-varying evidence reliability. link2 To model the choice and response time patterns, we developed a computational framework for fitting generalized drift-diffusion models, which flexibly accommodate diverse evidence accumulation strategies. We found that a dynamic urgency signal and leaky integration, in combination with two independent forms of reward biases, best capture behavior. We also tested how temporal structure influences urgency by systematically manipulating the temporal structure of sensory evidence, and found that the time course of urgency was affected by temporal context. Overall, our approach identified key components of cognitive mechanisms for incorporating temporal and reward structure into decisions.SIGNIFICANCE STATEMENT In everyday life, decisions are influenced by many factors, including reward structures and stimulus timing. While reward and timing have been characterized in isolation, ecologically valid decision-making involves a multiplicity of factors acting simultaneously. This raises questions about whether the same decision-making strategy is used when these two factors are concurrently manipulated. To address these questions, we trained rhesus monkeys to perform a novel decision-making task with both reward asymmetry and temporal uncertainty. In order to understand their strategy and hint at its neural mechanisms, we used the new generalized drift diffusion modeling framework to model both reward and timing mechanisms. We found two of each reward and timing mechanisms are necessary to explain our data.A hyperexcitable state and spontaneous activity of nociceptors have been suggested to play a critical role in the development of chronic neuropathic pain following spinal cord injury (SCI). In male rats, we employed the action potential-clamp technique to determine the underlying ionic mechanisms responsible for driving SCI-nociceptors to a hyperexcitable state and for triggering their spontaneous activity. We found that the increased activity of low voltage activated T-type calcium channels induced by the injury sustains the bulk (∼60-70%) of the inward current active at subthreshold voltages during the interspike interval in SCI-nociceptors, with a modest contribution (∼10-15%) from tetrodotoxin (TTX)-sensitive and TTX-resistant sodium channels and hyperpolarization-activated cyclic nucleotide-gated (HCN) channels. In current-clamp recordings, inhibition of T-type calcium channels with 1 μm TTA-P2 reduced both the spontaneous and the evoked firing in response to current injections in SCI-nociceptors to a leused to treat SCI-induced neuropathic pain, but their efficacy is very limited. link3 A hyperexcitable state and spontaneous activity of SCI-nociceptors have been proposed as a possible underlying cause for the development of chronic neuropathic pain following SCI. Here, QNZ show that the increased activity of T-type calcium channels induced by the injury plays a major role in driving SCI-nociceptors to a hyperexcitable state and for promoting their spontaneous activity, suggesting that T-type calcium channels may represent a pharmacological target to treat SCI-induced neuropathic pain.In order for the so-called strengthened impairment argument (SIA) to succeed, it must posit some reason R that causing fetal alcohol syndrome (FAS) is immoral, one that also holds in cases of abortion. In formulating SIA, Blackshaw and Hendricks borrow from Don Marquis to claim that the reason R that causing FAS is immoral lies in the fact that it deprives an organism of a future like ours (an FLO). I argue here that SIA fails to show that it is immoral to cause FAS and abort fetuses that will not be born because it deprives them of an FLO. This is because fetuses that will not be born have no chance of having an FLO in the first place, so causing FAS for and aborting them cannot deprive them of one. I then consider three responses to my argument. I conclude that each fails. SIA does not accomplish its task of showing why it is immoral to impair fetuses that will not be born. Perhaps it can accomplish the task of showing why it is immoral to impair fetuses that will be born, but not without sacrificing at least some of its alleged significance.Many healthcare goods, such as surgical instruments, textiles and gloves, are manufactured in unregulated factories and sweatshops where, amongst other labour rights violations, workers are subject to considerable occupational health risks. In this paper we undertake an ethical analysis of the supply of sweatshop-produced surgical goods to healthcare providers, with a specific focus on the National Health Service of the United Kingdom. We contend that while labour abuses and occupational health deficiencies are morally unacceptable in the production of any commodity, an additional wrong is incurred when the health of certain populations is secured in ways that endanger the health and well-being of people working and living elsewhere. While some measures have been taken to better regulate the supply chain to healthcare providers in the UK, further action is needed to ensure that surgical goods are sourced from suppliers who protect the labour and occupational health rights of their workers.As research involving gene editing continues to advance, we are headed in the direction of being able to modify the human germline. Should we reach a point where an argument can be made that the benefits of preventing unborn children and future generations from inheriting genetic conditions that cause tremendous suffering outweigh the risks associated with altering the human germline, the next step will be to design clinical trials using this technology in humans. These clinical trials will likely require careful follow-up and monitoring of future generations born with altered genes. This paper addresses some of the ethical issues raised by intergenerational monitoring and sets out to show that these issues can be avoided with careful consideration and clinical trial design.
High grade endometrial stromal sarcoma is a rare and highly malignant tumor that lacks a prognostic model. The aim of this study was to develop a prognostic nomogram predicting the overall survival of patients with high grade endometrial stromal sarcoma.

Clinical data for patients were derived from the Surveillance Epidemiology, and End Results database. Cox analysis and Akaike's information criterion were used to construct the nomogram. The concordance index, time dependent receiver operating characteristic curve, and calibration plot were used to evaluate the discriminative and calibrating capability. The net reclassification index, integrated discrimination improvement, and concordance index change were also compared between the nomogram and the International Federation of Gynecology and Obstetrics (FIGO) stage. Clinical benefit was evaluated using decision curve analysis. The patients were separated into groups with low and high nomogram risk scores. Kaplan-Meier curve analysis and Cox analysis were usease stage alone. Patients with a high risk score had distinctly poorer survival than those with low risk scores.

A prognostic nomogram in patients with high grade endometrial stromal sarcoma exhibited favorable prognostic discrimination and survival prediction ability compared with FIGO stage.
A prognostic nomogram in patients with high grade endometrial stromal sarcoma exhibited favorable prognostic discrimination and survival prediction ability compared with FIGO stage.
Limited information exists regarding risk reduction strategies for women with moderate and low penetrance ovarian cancer susceptibility mutations. We sought to assess current risk reduction practice patterns for carriers of these mutations through a survey of members of the Society of Gynecologic Oncology.

Society of Gynecologic Oncology members were emailed a survey consisting of two vignettes (1) a 35-year-old premenopausal woman; (2) a 55-year-old postmenopausal woman with comorbidities. Each vignette contained sub-scenarios in which the patient had either a
(relative risk (RR)=30-60),
(RR=5.0), or
(RR=1.5-2.0) mutation. Respondents were queried about their preferred management approach. Summary statistics were performed to describe results of the survey. We used χ
testing for statistical analyses, comparing results according to mutation type and demographic information.

A total of 193 (15%) of 1284 Society of Gynecologic Oncology members responded. For the premenopausal woman, 99%, 80%, a was a lack of consensus about management of the moderate and low penetrance mutations, suggesting that more data regarding age specific risks and appropriate risk reduction strategies for these alterations are needed.After ejaculation, mammalian spermatozoa must undergo a process known as capacitation in order to successfully fertilize the oocyte. Several post-translational modifications occur during capacitation, including sialylation, which despite being limited to a few proteins, seems to be essential for proper sperm-oocyte interaction. Regardless of its importance, to date, no single study has ever identified nor quantified which glycoproteins bearing terminal sialic acid (Sia) are altered during capacitation. Here we characterize sialylation during mouse sperm capacitation. Using tandem MS coupled with liquid chromatography (LC-MS/MS), we found 142 nonreductant peptides, with 9 of them showing potential modifications on their sialylated oligosaccharides during capacitation. As such, N-linked sialoglycopeptides from C4b-binding protein, endothelial lipase (EL), serine proteases 39 and 52, testis-expressed protein 101 and zonadhesin were reduced following capacitation. In contrast, mitochondrial aconitate hydratase (aconitase; ACO2), a TCA cycle enzyme, was the only protein to show an increase in Sia content during capacitation. Interestingly, although the loss of Sia within EL (N62) was accompanied by a reduction in its phospholipase A1 activity, a decrease in the activity of ACO2 (i.e. stereospecific isomerization of citrate to isocitrate) occurred when sialylation increased (N612). The latter was confirmed by N612D recombinant protein tagged with both His and GFP. The replacement of Sia for the negatively charged Aspartic acid in the N612D mutant caused complete loss of aconitase activity compared with the WT. Computer modeling show that N612 sits atop the catalytic site of ACO2. The introduction of Sia causes a large conformational change in the alpha helix, essentially, distorting the active site, leading to complete loss of function. These findings suggest that the switch from oxidative phosphorylation, over to glycolysis that occurs during capacitation may come about through sialylation of ACO2.
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