218 research outputs found

    Emotional Support Animals, Service Animals, and Pets on Campus

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    For decades, universities have been accommodating physically disabled students who require guide dogs and other types of service animals. Within the past several years, however, mentally disabled students have increasingly petitioned colleges with no-pet policies to permit them to bring their animals on campus because they need a companion or emotional support animal to make college life easier and to reduce their stress, loneliness, depression, and/or anxiety. Institutions that unlawfully reject such requests are finding themselves in court and charged with disability discrimination. Schools are understandably confused about their obligation, if any, to waive their no-pet rules under these circumstances. This article discusses pets on campus and provides administrators guidance with respect to this increasingly contentious issue and to keep their organizations ā€œout of the legal dog house.

    Womenā€™s Empowerment Campaigns: Helpful or Harmful to the Workplace?

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    Womenā€™s empowerment campaigns create greater equality for women in numerous areas including social, political, economic, and occupational fields. However, the current #MeToo and Timeā€™s Up movements have become increasingly hostile toward men. This hostility has developed an anti-male environment that may be perceived by men as unfair restrictions on their behavior and boundaries on their autonomy. This leads to adoption of behavior and attitudes opposite of the intended effects and that may do more harm than good. This response is explained as psychological reactance. The authors discuss its harmful impact in the workplace offer suggestions for mitigating these situations

    How managers use the Stockdale Paradox to balance ā€œthe now and the nextā€

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    Recent discussions of leadership paradoxes have suggested that managers who can hold seemingly opposed, yet interrelated perspectives, are more adaptive and effective. One such paradox that has received relatively little attention is the ā€œStockdale Paradox,ā€ named after Admiral James Stockdale, an American naval officer who was held captive for seven and one-half years during the Vietnam War and survived imprisonment in large part because he held beliefs of optimism about the future, while simultaneously acknowledging the current reality of the desperate situation in which he found himself. This contradictory tension enabled him and his followers to emerge from their situation not just unbroken, but stronger. Such paradoxical thinking has been empirically supported by mental contrasting research demonstrating the effectiveness of visualizing a positive future yet recognizing the reality of the current situation. This apparent dichotomy provides an important lesson for leaders who must remain optimistic, yet face the reality of their present condition, and is symbolic of an overarching, general tension leaders face in addressing ā€œthe now and the next.

    Never Underestimate the Power of a Backhoe: Integrating Single Points of Failure into Strategic Planning

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    SWOT (strengths, weaknesses, opportunities, threats) analysis is probably used more often than any other management technique in strategic decision making. There appears to be a greater emphasis, however, on identifying strengths and opportunities while weaknesses and threats are examined less closely. Such bias may be problematic because firms may overlook single points of failure (SPOFs), which are elements that, upon malfunction, render an entire system unavailable or unreliable. These threats and weaknesses are most often presented in information technology and engineering discussions of equipment, machine, and device breakdowns, but may have applicability in a number of other areas important to organizations including people; materials and supplies; methods and processes; and shock eventsā€”natural and human-made disasters. To be resilient in todayā€™s 24-7, 365 days a year global business world, it is critical that organizations effectively anticipate, evaluate, prepare for, and mitigate SPOF risks that can have a seriously negative impact on a firmā€™s performance. The paper concludes with a three-step approach to help managers reduce and effectively respond to SPOFs. Companies that integrate the concept of SPOFs into their strategic planning could develop high-impact management skill, leading to improved corporate profitability

    Central role of dendritic cells in pulmonary arterial hypertension in human and mice

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    The pathogenesis of idiopathic pulmonary arterial hypertension (IPAH) is not fully understood, but evidence is accumulating that immune dysfunction plays a significant role. We previously reported that 31-week-old Tnfaip3(DNGR1-KO) mice develop pulmonary hypertension (PH) symptoms. These mice harbor a targeted deletion of the TNF alpha-induced protein-3 (Tnfaip3) gene, encoding the NF-kappa B regulatory protein A20, specifically in type I conventional dendritic cells (cDC1s). Here, we studied the involvement of dendritic cells (DCs) in PH in more detail. We found various immune cells, including DCs, in the hearts of Tnfaip3(DNGR1-KO) mice, particularly in the right ventricle (RV). Secondly, in young Tnfaip3(DNGR1-KO) mice, innate immune activation through airway exposure to toll-like receptor ligands essentially did not result in elevated RV pressures, although we did observe significant RV hypertrophy. Thirdly, PH symptoms in Tnfaip3(DNGR1-KO) mice were not enhanced by concomitant mutation of bone morphogenetic protein receptor type 2 (Bmpr2), which is the most affected gene in PAH patients. Finally, in human IPAH lung tissue we found co-localization of DCs and CD8+ T cells, representing the main cell type activated by cDC1s. Taken together, these findings support a unique role of cDC1s in PAH pathogenesis, independent of general immune activation or a mutation in the Bmpr2 gene

    Mapping interactions with the chaperone network reveals factors that protect against tau aggregation.

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    A network of molecular chaperones is known to bind proteins ('clients') and balance their folding, function and turnover. However, it is often unclear which chaperones are critical for selective recognition of individual clients. It is also not clear why these key chaperones might fail in protein-aggregation diseases. Here, we utilized human microtubule-associated protein tau (MAPT or tau) as a model client to survey interactions between ~30 purified chaperones and ~20 disease-associated tau variants (~600 combinations). From this large-scale analysis, we identified human DnaJA2 as an unexpected, but potent, inhibitor of tau aggregation. DnaJA2 levels were correlated with tau pathology in human brains, supporting the idea that it is an important regulator of tau homeostasis. Of note, we found that some disease-associated tau variants were relatively immune to interactions with chaperones, suggesting a model in which avoiding physical recognition by chaperone networks may contribute to disease

    The impact of patient-reported frailty on cardiovascular outcomes in elderly patients after non-ST-acute coronary syndrome

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    Background: As life expectancy increases, the population of older individuals with coronary artery disease and frailty is growing. We aimed to assess the impact of patient-reported frailty on the treatment and prognosis of elderly early survivors of non-ST-elevation acute coronary syndrome (NSTE-ACS). Methods: Frailty data were obtained from two prospective trials, POPular Age and the POPular Age Registry, which both assessed elderly NSTE-ACS patients. Frailty was assessed one month after admission with the Groningen Frailty Indicator (GFI) and was defined as a GFI-score of 4 or higher. In these early survivors of NSTE-ACS, we assessed differences in treatment and 1-year outcomes between frail and non-frail patients, considering major adverse cardiovascular events (MACE, including cardiovascular mortality, myocardial infarction, and stroke) and major bleeding. Results: The total study population consisted of 2192 NSTE-ACS patients, aged ā‰„70 years. The GFI-score was available in 1320 patients (79 Ā± 5 years, 37% women), of whom 712 (54%) were considered frail. Frail patients were at higher risk for MACE than non-frail patients (9.7% vs. 5.1%, adjusted hazard ratio [HR] 1.57, 95% confidence interval [CI] 1.01ā€“2.43, p = 0.04), but not for major bleeding (3.7% vs. 2.8%, adjusted HR 1.23, 95% CI 0.65ā€“2.32, p = 0.53). Cubic spline analysis showed a gradual increase of the risk for clinical outcomes with higher GFI-scores. Conclusions: In elderly NSTE-ACS patients who survived 1-month follow-up, patient-reported frailty was independently associated with a higher risk for 1-year MACE, but not with major bleeding. These findings emphasize the importance of frailty screening for risk stratification in elderly NSTE-ACS patients.</p

    Modeling Intrinsically Disordered Proteins with Bayesian Statistics

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    The characterization of intrinsically disordered proteins is challenging because accurate models of these systems require a description of both their thermally accessible conformers and the associated relative stabilities or weights. These structures and weights are typically chosen such that calculated ensemble averages agree with some set of prespecified experimental measurements; however, the large number of degrees of freedom in these systems typically leads to multiple conformational ensembles that are degenerate with respect to any given set of experimental observables. In this work we demonstrate that estimates of the relative stabilities of conformers within an ensemble are often incorrect when one does not account for the underlying uncertainty in the estimates themselves. Therefore, we present a method for modeling the conformational properties of disordered proteins that estimates the uncertainty in the weights of each conformer. The Bayesian weighting (BW) formalism incorporates information from both experimental data and theoretical predictions to calculate a probability density over all possible ways of weighting the conformers in the ensemble. This probability density is then used to estimate the values of the weights. A unique and powerful feature of the approach is that it provides a built-in error measure that allows one to assess the accuracy of the ensemble. We validate the approach using reference ensembles constructed from the five-residue peptide met-enkephalin and then apply the BW method to construct an ensemble of the K18 isoform of the tau protein. Using this ensemble, we indentify a specific pattern of long-range contacts in K18 that correlates with the known aggregation properties of the sequence.National Institutes of Health (U.S.) (NIH Grant 5R21NS063185-02

    Deep-Inelastic Inclusive ep Scattering at Low x and a Determination of alpha_s

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    A precise measurement of the inclusive deep-inelastic e^+p scattering cross section is reported in the kinematic range 1.5<= Q^2 <=150 GeV^2 and 3*10^(-5)<= x <=0.2. The data were recorded with the H1 detector at HERA in 1996 and 1997, and correspond to an integrated luminosity of 20 pb^(-1). The double differential cross section, from which the proton structure function F_2(x,Q^2) and the longitudinal structure function F_L(x,Q^2) are extracted, is measured with typically 1% statistical and 3% systematic uncertainties. The measured partial derivative (dF_2(x,Q^2)/dln Q^2)_x is observed to rise continuously towards small x for fixed Q^2. The cross section data are combined with published H1 measurements at high Q^2 for a next-to-leading order DGLAP QCD analysis.The H1 data determine the gluon momentum distribution in the range 3*10^(-4)<= x <=0.1 to within an experimental accuracy of about 3% for Q^2 =20 GeV^2. A fit of the H1 measurements and the mu p data of the BCDMS collaboration allows the strong coupling constant alpha_s and the gluon distribution to be simultaneously determined. A value of alpha _s(M_Z^2)=0.1150+-0.0017 (exp) +0.0009-0.0005 (model) is obtained in NLO, with an additional theoretical uncertainty of about +-0.005, mainly due to the uncertainty of the renormalisation scale.Comment: 68 pages, 24 figures and 18 table
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