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Chronic intermittent hypoxia (CIH), an animal model of sleep apnea, has been shown to alter the activity of second-order chemoreceptor neurons in the caudal nucleus of the solitary tract (cNTS). Although numerous studies have focused on excitatory plasticity, few studies have explored CIH-induced plasticity impacting inhibitory inputs to NTS neurons, and the roles of GABAergic and glycinergic inputs on heightened cNTS excitability following CIH are unknown. In addition, changes in astrocyte function may play a role in cNTS plasticity responses to CIH. This study tested the effects of a 7-day CIH protocol on miniature inhibitory postsynaptic currents (mIPSCs) in cNTS neurons receiving chemoreceptor afferents. Normoxia-treated rats primarily displayed GABA mIPSCs, whereas CIH-treated rats exhibited a shift toward combined GABA/glycine-mediated mIPSCs. CIH increased glycinergic mIPSC amplitude and area. This shift was not observed in dorsal motor nucleus of the vagus neurons or cNTS cells from females. Immunohistochemistry showed that strengthened glycinergic mIPSCs were associated with increased glycine receptor protein and were dependent on receptor trafficking in CIH-treated rats. In addition, CIH altered astrocyte morphology in the cNTS, and inactivation of astrocytes following CIH reduced glycine receptor-mediated mIPSC frequency and overall mIPSC amplitude. In cNTS, CIH produced changes in glycine signaling that appear to reflect increased trafficking of glycine receptors to the cell membrane. Increased glycine signaling in cNTS associated with CIH also appears to be dependent on astrocytes. Additional studies will be needed to determine how CIH influences glycine receptor expression and astrocyte function in cNTS.

Dilutional hyponatremia associated with liver cirrhosis is due to inappropriate release of arginine vasopressin (AVP). Elevated plasma AVP causes water retention resulting in a decrease in plasma osmolality. Cirrhosis, in this study caused by ligation of the common bile duct (BDL), leads to a decrease in central vascular blood volume and hypotension, stimuli for nonosmotic AVP release. The A1/A2 neurons stimulate the release of AVP from the supraoptic nucleus (SON) in response to nonosmotic stimuli. We hypothesize that the A1/A2 noradrenergic neurons support chronic release of AVP in cirrhosis leading to dilutional hyponatremia. Adult, male rats were anesthetized with 2–3% isoflurane (mixed with 95% O2/5% CO2) and injected in the SON with anti-dopamine β-hydroxylase (DBH) saporin (DSAP) or vehicle followed by either BDL or sham surgery. Plasma copeptin, osmolality, and hematocrit were measured. Brains were processed for ΔFosB, dopamine β-hydroxylase (DBH), and AVP immunohistochemistry. DSAP injection: 1) significantly reduced the number of DBH immunoreactive A1/A2 neurons (A1, P < 0.0001; A2, P = 0.0014), 2) significantly reduced the number of A1/A2 neurons immunoreactive to both DBH and ΔFosB positive neurons (A1, P = 0.0015; A2, P < 0.0001), 3) reduced the number of SON neurons immunoreactive to both AVP and ΔFosB ( P < 0.0001), 4) prevented the increase in plasma copeptin observed in vehicle-injected BDL rats ( P = 0.0011), and 5) normalized plasma osmolality and hematocrit (plasma osmolality, P = 0.0475; hematocrit, P = 0.0051) as compared with vehicle injection. Our data suggest that A1/A2 neurons contribute to increased plasma copeptin and hypoosmolality in male BDL rats.

Background: Rodent Parkinson’s disease (PD) models are valuable to interrogate neurobiological mechanisms of exercise that mitigate motor impairment. Translating these mechanisms to human PD must account for physical capabilities of the patient. Objective: To establish cardiovascular parameters as a common metric for cross-species translation of aerobic exercise impact. Method: We evaluated aerobic exercise impact on heart rate (HR) in 21 early-stage PD subjects (Hoehn Yahr ≤1.5) exercising in non-contact boxing training for ≥3 months, ≥3x/week. In 4-month-old Pink1 knockout (KO) rats exercising in a progressively-increased treadmill speed regimen, we determined a specific treadmill speed that increased HR to an extent similar in human subjects. Results: After completing aerobic exercise for ∼30 min, PD subjects had increased HR∼35% above baseline (∼63% maximum HR). Motor and cognitive test results indicated the exercising subjects completed the timed up and go (TUG) and trail-making test (TMT-A) in significantly less time versus exercise-naïve PD subjects. In KO and age-matched wild-type (WT) rats, treadmill speeds of 8–10 m/min increased HR up to 25% above baseline (∼67% maximum HR), with no further increases up to 16 m/min. Exercised KO, but not WT, rats showed increased locomotor activity compared to an age-matched exercise-naïve cohort at 5 months old. Conclusion: These proof-of-concept results indicate HR is a cross-species translation parameter to evaluate aerobic exercise impact on specific motor or cognitive functions in human subjects and rat PD models. Moreover, a moderate intensity exercise regimen is within the physical abilities of early-stage PD patients and is therefore applicable for interrogating neurobiological mechanisms in rat PD models.

Bacterial infections and impaired mitochondrial DNA dynamics are associated with adverse pregnancy outcomes. Unmethylated cytosine-guanine dinucleotide (CpG) motifs are common in bacterial and mitochondrial DNA and act as potent immunostimulators. Here, we tested the hypothesis that exposure to CpG oligonucleotides (ODN) during pregnancy would disrupt blood pressure circadian rhythms and the placental molecular clock machinery, mediating aberrant fetoplacental growth dynamics. Rats were repeatedly treated with CpG ODN in the 3rdtrimester (gestational day, GD, 14, 16, 18) and euthanized on GD20 (near term) or with a single dose of CpG ODN and euthanized 4 hours after treatment on GD14. Hemodynamic circadian rhythms were analyzed via Lomb-Scargle periodogram analysis on 24-h raw data collected continuously via radiotelemetry. Ap-value ≥ 0.05 indicates the absence of a circadian rhythm. Following the first treatment with CpG ODN, maternal systolic and diastolic blood pressure circadian rhythms were lost (p≥ 0.05). Blood pressure circadian rhythm was restored by GD16 and remained unaffected after the second treatment with CpG ODN (p< 0.0001). Diastolic blood pressure circadian rhythm was again lost after the last treatment on GD18 (p≥ 0.05). CpG ODN increased placental expression ofPer2andPer3andTnfα(p≤ 0.05) and affected fetoplacental growth dynamics, such as reduced fetal and placental weights were disproportionately associated with increases in the number of resorptions in ODN-treated dams compared to controls. In conclusion, gestational exposure to unmethylated CpG DNA dysregulates placental molecular clock network and fetoplacental growth dynamics and disrupts blood pressure circadian rhythms.

Despite the general narrative that we are in a period of global democratic decline, there have been surprisingly few empirical studies to assess whether this is systematically true. Most existing studies of backsliding rely heavily, if not entirely, on subjective indicators which rely on expert coder judgement. We survey other more objective indicators of democracy (such as incumbent performance in elections), and find little evidence of global democratic decline over the last decade. To explain the discrepancy between trends in subjective and objective indicators, we develop formal models that consider the role of coder bias and leaders strategically using more subtle undemocratic action. The simplest explanation is that recent declines in average democracy scores are driven by changes in coder bias. While we cannot rule out the possibility that the world is experiencing major democratic backsliding almost exclusively in ways which require subjective judgement to detect, this claim not justified by existing evidence.

Does motivated reasoning harm democratic accountability? Substantial evidence from political behavior research indicates that voters have “directional motives” beyond accuracy, which is often taken as evidence that they are ill equipped to hold politicians accountable. We develop a model of electoral accountability with voters as motivated reasoners. Directional motives have two effects: (1) divergence—voters with different preferences hold different beliefs, and (2) desensitization—the relationship between incumbent performance and voter beliefs is weakened. While motivated reasoning does harm accountability, this is generally driven by desensitized voters rather than polarized partisans with politically motivated divergent beliefs. We also analyze the relationship between government performance and vote shares, showing that while motivated reasoning always weakens this relationship, we cannot infer that accountability is also harmed. Finally, we show that our model can be mapped to standard models in which voters are fully Bayesian but have different preferences or information.

Beliefs can be incorrect or biased in many ways. I propose a unifying microfoundation for many well-documented biases using ideas from information theory. The common theme is that subjective beliefs are the solution to an optimization problem where one goal is accuracy, formalized by minimizing Kullback-Leibler divergence from the objective belief. Correct beliefs are a special case where accuracy is the only goal. Other goals or constraints produce biases such as motivated beliefs, partition dependence, anchoring, overconfidence, confirmation bias, base-rate neglect, and conservatism.

We investigated the sensitivity of a screening test for pelvic ring disruption, the AP pelvis radiograph, for clinically serious U-type sacral fractures which merit consultation with an orthopedic trauma specialist and may require transfer to a higher level of care. Retrospective clinical cohort of 63 consecutive patients presenting with U-type sacral fractures at one level 1 trauma referral center from January 2006 through December 2019. The sensitivity of the first AP pelvis radiograph obtained on admission, interpreted without reference to antecedent or concomitant pelvis computed tomography (CT) by a radiologist and a panel of three blinded orthopedic traumatologists, was determined against a reference diagnosis made from review of all pelvis radiographs, CT images, operative reports, and clinical documentation. Sensitivity of AP pelvis radiograph for U-type sacral fractures was 2% as interpreted by a radiologist and mean 12% (range 5–27%) as interpreted by orthopedic traumatologists with poor inter-rater agreement (Fleiss’ κ = 0.11). 94% of sacra were at obscured by radiographic artifact. The sensitivity of an AP pelvis radiograph is poor for U-type sacral fractures, whether interpreted by radiologists or orthopedic traumatologists. Pelvis CT should be considered as a screening test to rule out sacral fracture when the patient reports posterior pelvic pain, even if plain radiography demonstrates no injury or a minimally displaced pelvic ring disruption. Diagnostic level III

To conduct a home-visit program for nursing students, to improve student confidence and comfort completing home visits in the underserved region of Southside, Virginia. The project was conducted in a rural community, where 24 nursing students and 1 family nurse practitioner made home visits once a week from September to December 2020. Students were evaluated on both their understanding of community health nursing and home-visit comfort levels via an anonymous pre- and post-home-visit assessment. Thirteen of the twenty-four students (54%) completed both the pre- and post-surveys. Results of the paired sample t-tests showed a significant increase in students’ comfort level from before the visit (3.0769) to after the visit (3.3077, p = .005). Students’ confidence levels also increased from before the visit (2.6923) to after the visit (3.3846, p = .006). Nursing educators are challenged to provide nursing students with the knowledge and skills needed to provide competent and compassionate evidence-based care in the field. Nursing student reported confidence in their nursing skills in the field after completing the home visit. Future research is needed on the benefit of completing home visits in nursing education programs.

Objective To discuss optimal treatment strategy for spindle cell oncocytoma (SCO) of the pituitary gland. Methods Institutional cases were retrospectively reviewed. A systematic literature search and subsequent quantitative synthesis were performed for further analysis. The detailed features were summarized and the tumor control rate (TCR) was calculated. Results Eighty-five patients (6 institutional and 79 literature) were included. The annual incidence was approximately 0.01–0.03/100,000. The mean age was 56 years. Vision loss was present in 60%. Seventy-three percent showed hormonal abnormalities. On magnetic resonance imaging, tumor was avidly enhancing, and the normal gland was commonly displaced anterosuperiorly. Evidence of hypervascularity was seen in 77%. Gross total resection (GTR) was achieved in only 24% because of its hypervascular, fibrous, and adhesive nature. The mean postoperative follow-up was 3.3 years for institutional cases and 2.3 years for the integrated cohort. The TCR was significantly better after GTR (5-year TCR, 75%; P = 0.012) and marginally better after non-GTR + upfront radiotherapy (5-year TCR, 76%; P = 0.103) than after non-GTR alone (5-year TCR, 24%). The TCRs for those with low Ki-67 index (≤5%) were marginally better than those with higher Ki-67 index (5-year rate, 57% vs. 23%; P = 0.110). Conclusions Frequent endocrine-related symptoms, hypervascular signs, and anterosuperior displacement of the gland support preoperative diagnosis of SCO. GTR seems to have better long-term tumor control, whereas the fibrous, hypervascular, and adhesive nature of SCO makes it difficult to achieve GTR. In patients with non-GTR, radiotherapy may help decrease tumor progression.

Introduction There is increased interest in the use of artificial intelligence-based (AI) software packages in the evaluation of neuroimaging studies for acute ischemic stroke. We studied whether, compared to standard image interpretation without AI, Brainomix e-ASPECTS software improved interobserver agreement and accuracy in detecting ASPECTS regions affected in anterior circulation LVO. Methods We included 60 consecutive patients with anterior circulation LVO who had TICI 3 revascularization within 60 minutes of their baseline CT. A total of 16 readers, including senior neuroradiologists, junior neuroradiologists and vascular neurologists participated. Readers interpreted CT scans on independent workstations and assessed final ASPECTS and evaluated whether each individual ASPECTS region was affected. Two months later, readers again evaluated the CT scans, but with assistance of e-ASPECTS software. We assessed interclass correlation coefficient for total ASPECTS and interobserver agreement with Fleiss’ Kappa for each ASPECTS region with and without assistance of the e-ASPECTS. We also assessed accuracy for the readers with and without e-ASPECTS assistance. In our assessment of accuracy, ground truth was the 24 hour CT in this cohort of patients who had prompt and complete revascularization. Results Interclass correlation coefficient for total ASPECTS without e-ASPECTS assistance was 0.395, indicating fair agreement compared, to 0.574 with e-ASPECTS assistance, indicating good agreement (P Conclusions Use of Brainomix e-ASPECTS software resulted in significant improvements in inter-rater agreement and accuracy of ASPECTS score evaluation in a large group of neuroradiologists and neurologists. e-ASPECTS software was more predictive of final infarct/ASPECTS than the overall group interpreting the CT scans with and without e-ASPECTS assistance.

A foundational premise in democratic theory is that political competition encourages parties to be responsive to voters. Parties have incentives to respond to the median voter's preferences in order to win elections, and should learn from the results of elections where their platforms diverge from what the electorate wants. However, parties may be subject to motivated reasoning, wanting to believe that the electorate favors their own policy preferences. We develop a repeated model of elections with motivated beliefs to explore how this bias affects how parties compete with one another for popular support. Motivated beliefs lead to excessive platform divergence, and allow parties to infer from poor electoral outcomes that elections are unfair rather than that their platforms are unpopular. Disagreement about the fairness of the electoral system increases over time, even if platform divergence decreases. Our analysis reveals how motivated beliefs inhibit parties' ability to learn what voters want while encouraging partisans to distrust the electoral process itself.

We analyze a formal model of policing where officers decide how to interact with members of two social groups, both while working and while socializing. The officers do not fully distinguish between their experiences of crime across these two contexts (“coarse thinking”), so they end up with excessively positive views of groups they socialize with and excessively negative views of those they police. This creates dual feedback loops as officers choose to socialize more with groups they view favorably and over-police those they view as “more criminal.” Policy interventions that increase positive contact with an overpoliced group can mitigate the officer’s discriminatory policing. However, this beneficial effect only persists if the policy intervention creates sustained positive contact. Our results provide a novel theoretical microfoundation for the contact hypothesis, and help explain why the effects of many policy interventions aimed at increasing positive contact are short-lived.

A large economic literature studies whether racial disparities in policing are explained by animus or by beliefs about group crime rates. But what if these beliefs are incorrect? We analyse a model where officers form beliefs using crime statistics, but don't properly account for the fact that they will detect more crime in more heavily policed communities. This creates a feedback loop where officers over-police groups that they (incorrectly) believe exhibit high crime rates. This inferential mistake can exacerbate discrimination even among officers with no animus and who sincerely believe disparities are driven by real differences in crime rates.

Chlorhexidine skin antisepsis is frequently recommended for most surgical procedures; however, it is unclear if these recommendations should apply to surgery involving traumatic contaminated wounds where povidone-iodine has previously been preferred. We aimed to compare the effect of aqueous 10% povidone-iodine versus aqueous 4% chlorhexidine gluconate on the risk of surgical site infection in patients who required surgery for an open fracture.We conducted a multiple-period, cluster-randomised, crossover trial (Aqueous-PREP) at 14 hospitals in Canada, Spain, and the USA. Eligible patients were adults aged 18 years or older with an open extremity fracture treated with a surgical fixation implant. For inclusion, the open fracture required formal surgical debridement within 72 h of the injury. Participating sites were randomly assigned (1:1) to use either aqueous 10% povidone-iodine or aqueous 4% chlorhexidine gluconate immediately before surgical incision; sites then alternated between the study interventions every 2 months. Participants, health-care providers, and study personnel were aware of the treatment assignment due to the colour of the solutions. The outcome adjudicators and data analysts were masked to treatment allocation. The primary outcome was surgical site infection, guided by the 2017 US Centers for Disease Control and Prevention National Healthcare Safety Network reporting criteria, which included superficial incisional infection within 30 days or deep incisional or organ space infection within 90 days of surgery. The primary analyses followed the intention-to-treat principle and included all participants in the groups to which they were randomly assigned. This study is registered with ClinicalTrials.gov, NCT03385304.Between April 8, 2018, and June 8, 2021, 3619 patients were assessed for eligibility and 1683 were enrolled and randomly assigned to povidone-iodine (n=847) or chlorhexidine gluconate (n=836). The trial's adjudication committee determined that 45 participants were ineligible, leaving 1638 participants in the primary analysis, with 828 in the povidone-iodine group and 810 in the chlorhexidine gluconate group (mean age 44·9 years [SD 18·0]; 629 [38%] were female and 1009 [62%] were male). Among 1571 participants in whom the primary outcome was known, a surgical site infection occurred in 59 (7%) of 787 participants in the povidone-iodine group and 58 (7%) of 784 in the chlorhexidine gluconate group (odds ratio 1·11, 95% CI 0·74 to 1·65; p=0·61; risk difference 0·6%, 95% CI -1·4 to 3·4).For patients who require surgical fixation of an open fracture, either aqueous 10% povidone-iodine or aqueous 4% chlorhexidine gluconate can be selected for skin antisepsis on the basis of solution availability, patient contraindications, or product cost. These findings might also have implications for antisepsis of other traumatic wounds.US Department of Defense, Canadian Institutes of Health Research, McMaster University Surgical Associates, PSI Foundation.

Individuals, like researchers, often have to form beliefs about the political world from non-representative samples; e.g., their friends, what they see on TV, or content on social media. Substantial evidence indicates that many struggle to account for this selection problem, and generally form beliefs as if what they observe is representative. In this review, we provide a formal typology of how this phenomenon of selection neglect affects political beliefs. Homophily leads individuals to believe others’ traits and beliefs are closer to their own. The squeaky wheel effect biases beliefs towards more visible or vocal groups. And the man bites dog effect leads to excessive belief in extreme or unusual events. Selection neglect is a unifying way to understand disparate literatures on perceptions of the economy and demographics, beliefs about others beliefs, partisan media, and social media. Much empirical work is consistent with biased beliefs driven by selection neglect, but rarely directly tests this mechanism outside of lab settings. We discuss how future research can provide more direct evidence.

The complete genome sequence of Paraclostridium bifermentans was obtained by assembly of Illumina and Oxford Nanopore (ONT) reads. The sequence will enable study into the organism’s ability to biohydrogenate unsaturated acyl chains in the transformation of C20 polyunsaturated fatty acids (PUFAs) into the corresponding bioactive non-methylene-interrupted fatty acids (NMIFAs).

MRI is a powerful diagnostic tool with excellent soft tissue contrast that uses nonionizing radiation. These advantages make MRI an appealing modality for imaging the pregnant patient; however, specific risks inherent to the magnetic resonance environment must be considered. MRI may be performed without and/or with intravenous contrast, which adds further fetal considerations. The risks of MRI with and without intravenous contrast are reviewed as they pertain to the pregnant or lactating patient and to the fetus and nursing infant. Relevant issues for gadolinium-based contrast agents and ultrasmall paramagnetic iron oxide particles are reviewed.

We investigated the hypothesis that increasing fMRI temporal resolution using a multiband (MB) gradient echo-echo planar imaging (GRE-EPI) pulse sequence provides fMRI language maps of higher statistical quality than those acquired with a traditional GRE-EPI sequence. This prospective study enrolled 29 consecutive patients receiving language fMRI prior to a potential brain resection for tumor, AVM, or epilepsy. A 4-min rhyming task was performed at 3.0 Tesla with a traditional GRE-EPI pulse sequence (TR = 2000, TE = 30, matrix = 64/100%, slice = 4/0, FOV = 24, slices = 30, time points = 120) and an additional MB GRE-EPI pulse sequence with an acceleration factor of 6 (TR = 333, TE = 30, matrix 64/100%, slice = 4/0, FOV = 24, time points = 720). Spatially filtered t statistical maps were generated. Volumes of interest (VOIs) were drawn around activations at Broca’s, dorsolateral prefrontal cortex, Wernicke’s, and the visual word form areas. The t value maxima were measured for the overall brain and each of the VOIs. A paired t test was performed for the corresponding traditional and MB GRE-EPI measurements. The mean age of subjects was 42.6 years old (18–75). Sixty-two percent were male. The average overall brain t statistic maxima for the MB pulse sequence (t = 15.4) was higher than for the traditional pulse sequence (t = 9.3, p = < .0001). This also held true for Broca’s area (p < 0.0001), Wernicke’s area (p < .0001), dorsolateral prefrontal cortex (p < .0001), and the visual word form area (p < .0001). A MB GRE-EPI fMRI pulse sequence employing high temporal resolution provides clinical fMRI language maps of greater statistical significance than those obtained with a traditional GRE-EPI sequence.

Political decision makers make choices in a complex and uncertain world, where even the most qualified experts may not know what policies will succeed. Worse, if these experts care about their reputation for competence, they may be averse to admitting what they don’t know. We model the strategic communication of uncertainty, allowing for the salient reality that sometimes the effects of proposed policies are impossible to know. Our model highlights the challenge of getting experts to admit uncertainty, even when it is possible to check predictive success. Moreover, we identify a novel solution: checking features of the question that only good experts will infer—in particular, whether the effect of policies is knowable—can induce uninformed experts do say “I Don’t Know.”

Introduction: Hyponatremia due to elevated arginine vasopressin (AVP) secretion increases mortality in liver failure patients. No previous studies have addressed sex differences in hyponatremia in liver failure animal models. Objective: This study addressed this gap in our understanding of the potential sex differences in hyponatremia associated with increased AVP secretion. Methods: This study tested the role of sex in the development of hyponatremia using adult male, female, and ovariectomized (OVX) female bile duct-ligated (BDL) rats. Results: All BDL rats had significantly increased liver to body weight ratios compared to sham controls. Male BDL rats had hyponatremia with significant increases in plasma copeptin and FosB expression in supraoptic AVP neurons compared to male shams (all p < 0.05; 5–7). Female BDL rats did not become hyponatremic or demonstrate increased supraoptic AVP neuron activation and copeptin secretion compared to female shams. Plasma oxytocin was significantly higher in female BDL rats compared to female sham (p < 0.05; 6–10). This increase was not observed in male BDL rats. Ovariectomy significantly decreased plasma estradiol in sham rats compared to intact female sham (p < 0.05; 6–10). However, circulating estradiol was significantly elevated in OVX BDL rats compared to the OVX and female shams (p < 0.05; 6–10). Adrenal estradiol, testosterone, and dehydroepiandrosterone (DHEA) were measured to identify a possible source of circulating estradiol in OVX BDL rats. The OVX BDL rats had significantly increased adrenal estradiol along with significantly decreased adrenal testosterone and DHEA compared to OVX shams (all p < 0.05; 6–7). Plasma osmolality, hematocrit, copeptin, and AVP neuron activation were not significantly different between OVX BDL and OVX shams. Plasma oxytocin was significantly higher in OVX BDL rats compared to OVX sham. Conclusions: Our results show that unlike male BDL rats, female and OVX BDL rats did not develop hyponatremia, supraoptic AVP neuron activation, or increased copeptin secretion compared to female shams. Adrenal estradiol might have compensated for the lack of ovarian estrogens in OVX BDL rats.

The central puzzle of persuasion is why a receiver would listen to a sender who they know is trying to change their beliefs or behavior. This paper summarizes five approaches to solving this puzzle: (1) some messages are easier to send for those with favorable information (costly signaling), (2) the sender and receiver have common interest, (3) the sender messages are verifiable information, (4) the sender cares about their reputation for competence/honesty, and (5) the sender can commit to a messaging strategy (often called ``Bayesian Persuasion''). To explore the relative value of these approaches, I discuss which provide insight into prominent empirical findings on campaigns, partisan media, and lobbying. While models focusing on commitment have rapidly become prominent (if not dominant) in the recent theoretical literature on persuasion in political science and economics, the insights they provide are primarily technical, and are not particularly well-suited to explaining these phenomena.

Prominent theories propose that phenomena such as war and democratization occur when rulers cannot commit to future promises toward challengers. Different variants of these theories give divergent answers to a key question: how does the strength of a challenger affect prospects for bargaining breakdown and/or institutional reform? We provide a new answer by analyzing a model with a general distribution of the probability that the challenger would win a conflict in a given period (“threat”). The effect of the challenger’s underlying coercive strength depends on the relationship between their average and maximum threat. When the maximum threat is fixed and high, inherently weak challengers are prone to rebel in rare periods when they pose a high threat. However, if only inherently strong challengers pose a high maximum threat, then they are harder to buy off. These theoretical insights uncover key parameters on which empirical research must focus, which we apply to existing debates about democratization.

A wide variety of political behavior can be explained with costly signaling arguments. In most scenarios there are many potential ways that the sender could signal their type. I present some general results about the question of which costly signals are sent in a setting with multiple available technologies, and apply them to several domains. The first main result extends a commonly known fact from unidmensional continuous choice signaling problems: there is generally a unique PBE which meets the intuitive criterion, where the strong type uses the least costly signal which the weak type is unwilling to send. Under a natural parameterization, this involves signaling only on the dimension which the strong type has the largest comparative advantage in producing cheaply. However, this equilibrium may not be ideal from a welfare perspective. Finally, I present an extension where one way of signaling is inherently informative, using an example of a dictator signaling strength by holding an election. Equilibria with signaling on inherently informative dimensions tend to survive refinements and produce higher welfare.

To examine an association between idiopathic transclival cerebrospinal fluid (CSF) leak and notochordal lesions.This study consisted of the illustrations of institutional patients who underwent surgery for transclival CSF leak between January 1, 2009 and April 25, 2020 and comprehensive review of the existing literature conducted on April 25, 2020. The cases were classified based on the presumed etiologies that were originally proposed in the articles ("idiopathic" vs. "secondary"). The baseline characteristics were compared between the groups, and the surgical outcomes were summarized.In 3 institutional cases, ecchordosis physaliphora (EP) was confirmed at the fistula either pathologically (1) or radiologically (2). Among 42 literature cases, 28 were recognized as idiopathic, while 14 were secondary cases with histologically (n = 12) or radiologically (n = 2) confirmed notochordal lesion at the fistula. Thus, any notochordal lesions were histologically confirmed in 13 among a total of 45 cases (28.9%). Fourteen of the idiopathic cases had undescribed radiographic signs suggestive of small ecchordosis physaliphora at the fistula. Both idiopathic and secondary cases demonstrated resemblance in their ages (mean, 51.4 and 56.6 years; p = 0.102), female predominance (male, 36% vs. 25%; P = 0.521), no association with obesity (7% vs. 18%; P = 0.350) or increased intracranial pressure (7% vs. 6%; P = 1.000). All the fistulas were in the midline or paramidline clivus within several millimeters below the dorsum sellae. All the patients were treated surgically with a multilayer closure, resulting in a success rate of 93% with one surgery.Our analyses suggest the association of transclival CSF leak and notochord lesions. A prospective study is needed for definitive conclusion.

Background To strengthen the impact of cash transfers, these interventions have begun to be packaged as cash-plus programmes, combining cash with additional transfers, interventions, or services. The intervention’s complementary (“plus”) components aim to improve cash transfer effectiveness by targeting mediating outcomes or the availability of supplies or services. This study examined whether cash-plus interventions for infants and children, In a systematic review and meta analysis, Madison Little and colleagues examine whether cash-plus programmes combined with additional interventions are more effective than cash transfers alone in improving health and wellbeing outcomes for children under 5 in low and middle income countries., Author summary Why was this study done? Cash transfers (providing individuals or families direct cash payments) are an easy-to-implement intervention that has widespread impacts, but evidence suggests that these programmes do not universally improve child health and well-being. Cash-plus programmes (combining cash transfers with complementary interventions) have been proposed as a solution to maximise the effectiveness of cash transfers to improve the lives of children. Our study aimed to assess whether cash-plus programmes are more effective than cash alone in improving child health and wellbeing. What did the researchers do and find? We conducted a systematic review of 42 information sources and databases and found 17 studies that met the review criteria, of which 11 were meta-analysed. We identified 5 cash-plus programme categorisations: Cash + Nutrition Behaviour Change Communication, Cash + Food Transfers, Cash + Primary Healthcare, Cash + Psychosocial Stimulation, and Cash + Child Protection. Meta-analysis results suggest that only Cash + Food Transfers has added impact above cash alone, having significantly reduced odds of children experiencing stunted growth (OR = 0.82 (0.74, 0.92)). Narrative synthesis results suggest that Cash + Food Transfers in crisis contexts and Cash + Primary Healthcare may also have greater benefit than cash alone. What do these findings mean? There are few studies to date that evaluate the effectiveness of cash-plus programmes against cash alone, which leaves significant evidence gaps in our understanding of these interventions. Our findings suggest that not all cash-plus programme combinations are more effective than cash transfers alone but that combining cash with food transfers or primary healthcare may have added impact in improving child health and well-being. There was significant variation in impacts across studies and because of the limited number of studies identified for analysis, more research is needed in identifying effective plus-components and effective models of how these cash-plus programmes are designed and implemented.

Hyponatremia due to elevated arginine vasopressin (AVP) secretion increases mortality in liver failure patients. The mechanisms causing dysregulation of AVP secretion are unknown. Our hypothesis is that inappropriate AVP release associated with liver failure is due to increased brain-derived neurotrophic factor (BDNF) in the supraoptic nucleus (SON). BDNF diminishes GABAA inhibition in SON AVP neurons by increasing intracellular chloride through tyrosine receptor kinase B (TrkB) activation and downregulation of K+/Cl– cotransporter 2 (KCC2). This loss of inhibition could increase AVP secretion. This hypothesis was tested using shRNA against BDNF (shBDNF) in the SON in bile duct ligated (BDL) male rats. All BDL rats had significantly increased liver weight (p < 0.05; 6–9) compared to shams. BDL rats with control ­shRNA injections (BDL scrambled [SCR]) developed hyponatremia with increased plasma AVP and copeptin (CPP; all p < 0.05; 6–9) compared to sham groups. This is the first study to show that phosphorylation of TrkB is significantly increased along with significant decrease in phosphorylation of KCC2 in BDL SCR rats compared to the sham rats (p < 0.05;6–8). Knockdown of BDNF in the SON of BDL rats (BDL shBDNF) significantly increased plasma osmolality and hematocrit compared to BDL SCR rats (p < 0.05; 6–9). The BDL shBDNF rats had significant (p < 0.05; 6–9) decreases in plasma AVP and CPP concentration compared to BDL SCR rats. The BDNF knockdown also significantly blocked the increase in TrkB phosphorylation and decrease in KCC2 phosphorylation (p < 0.05; 6–8). The results indicate that BDNF produced in the SON contributes to increased AVP secretion and hyponatremia during liver failure.