Dispersion γZ\gamma Z-box correction to the weak charge of the proton

We consider elastic scattering of electrons off a proton target. The parity violating (PV) asymmetry arises at leading order in $\alpha$ due to interference of $\gamma$ and $Z$ exchange. The radiative corrections to this leading mechanism were calculated in the literature and included in experimental analyses, except for $\gamma Z$ box and cross-box contributions. We present here a dispersion calculation of these corrections in forward kinematics. We demonstrate that at the GeV energies of current PV experiments, such corrections are not suppressed by the small vector weak charge of the electron, as occurs in the atomic PV. Our results suggest that the current theoretical uncertainty in the analysis of the QWEAK experiment might be substantially underestimated, and more accurate account of the dispersion corrections are needed in order to interprete the PV data.Comment: 4 pages, 3 figures, revtex

Novelty Induces Behavioural And Glucocorticoid Responses In A Songbird Artificially Selected For Divergent Personalities

Stress physiology is thought to contribute to individual differences in behaviour. In part this reflects the fact that canonical personality measures consist of responses to challenges, including novel objects and environments. Exposure to novelty is typically assumed to induce a moderate increase in glucocorticoids (CORT), although this has rarely been tested. We tested this assumption using great tits, Parus major, selected for divergent personalities (bold-fast and shy-slow explorers), predicting that the shy birds would exhibit higher CORT following exposure to a novel object. We also scored behavioural responses to the novel object, predicting that bold birds would more frequently approach the novel object and exhibit more abnormal repetitive behaviours. We found that the presence of a novel object did induce a moderate CORT response, but selection lines did not differ in the magnitude of this response. Furthermore, although both selection lines showed a robust CORT elevation to a subsequent restraint stressor, the CORT response was stronger in bold birds and this effect was specific to novel object exposure. Shy birds showed a strong positive phenotypic correlation between CORT concentrations following the novel object exposure and the subsequent restraint stress. Behaviourally, the selection lines differed in their response during novel object exposure: as predicted, bold birds more frequently approached the novel object and shy birds more strongly decreased overall locomotion during the novel object trial, but birds from both selection lines showed significant and similar frequencies of abnormal repetitive behaviours during novel object exposure. Our findings support the hypothesis that personality emerges as a result of correlated selection on behaviour and underlying endocrine mechanisms and suggest that the relationship between endocrine stress physiology and personality is context dependent

Worth a thousand words?:Visual concept mapping of the quality of life of people with severe mental health problems

Objectives: Conventional approaches to quality of life (QoL) measurement rely heavily on verbal, language-based communication. They require respondents to have significant cognitive and verbal ability, making them potentially unsuitable for people with severe mental health problems. To facilitate an alternative approach to QoL assessment, the current study aims to develop an alternative, visual representation of QoL for people with severe mental health problems. Methods: An alternative, visual adaptation of the concept mapping method was used to construct this visual representation of QoL. Eighty-two participants (i.e., patients, care professionals, and family members) contributed to this study. Results were processed statistically to construct the concept map. Results: The concept map contains 160 unique visual statements, grouped into 8 clusters labelled (1) Support and Attention, (2) Social Contacts, (3) Happiness and Love, (4) Relaxation and Harmony, (5) Leisure, (6) Lifestyle, (7) Finances, and (8) Health and Living. Examples of visual statements are pictures of family silhouettes, romantic couples, natural scenes, houses, sports activities, wallets and coins, smiley faces, and heart shapes. The clusters were interpreted and labelled by participants. Conclusions: Almost all of the statements correspond to clusters found in previous (non-visual) QoL research. Hence, QoL domains can also be presented visually

Psychometric properties of the QoL-ME:A visual and personalized quality of life assessment app for people with severe mental health problems

Background: Quality of Life (QoL) assessment in people with severe mental health problems may benefit from improved personalization and accessibility. Therefore, an innovative, digital, visual, and personalized QoL assessment app for people with severe mental health problems was recently developed: the QoL-ME. The aim of this study was to evaluate the psychometric quality of the QoL-ME by assessing its reliability, validity, and responsiveness. Methods: To examine the reliability of the QoL-ME, the internal consistency of its subscales was assessed using Cronbach's Alpha. Correlations between the QoL-ME and the MANSA were computed to appraise the construct validity of the QoL-ME. Internal responsiveness was evaluated using the standardized response mean and external responsiveness was investigated using hierarchical regression. Results: Cronbach's Alpha's of the subscales of the QoL-ME ranged between 0.5 and 0.84. In accordance with expectations, the language-based core version of the QoL-ME correlated strongly (r = between 0.55 and 0.76) with the MANSA, whilst the picture-based additional modules of the QoL-ME correlated moderately (r = 0.3) with the MANSA. The standardized response mean was 0.23 and the regression model revealed a coefficient β of −0.01. Conclusions: The QoL-ME has adequate psychometric properties. In comparison with similar pictorial instruments, both the QoL-ME's reliability and validity can be considered as sufficient. The results indicate that the responsiveness of the QoL-ME is insufficient. Additional research is needed to evaluate and potentially modify the instrument to improve its responsiveness

Pharmacokinetics of amphotericin B after accidental overdose in an adult critically ill patient treated with plasmapheresis: a case report and review of literature

Amphotericin B is a broad-spectrum antifungal agent that is used in the treatment of systemic fungal infections. We describe the case of a 62-year-old female patient with recent aneurysmal subarachnoid hemorrhage who was treated for suspected ventriculitis and a fungal coinfection. Instead of liposomal amphotericin B (L-AmB), 465 mg (5 mg/kg) amphotericin B deoxycholate (DOC) was inadvertently administered, leading to refractory shock with multiple organ failure and requiring mechanical ventilation. Since an overdose of amphotericin B can lead to fatal consequences and has a half-life of 15 days, plasmapheresis was started. The serum concentration decreased from 1.32 µg/mL to 0.62 µg/mL before plasmapheresis, demonstrating a mean half-life of 49 hours. After two plasmapheresis sessions, the serum concentration further dropped to 0.26 µg/mL, demonstrating a mean half-life of 17 hours. In contrast, the third plasmapheresis session had no effect on serum concentration. The patient made a full recovery, potentially facilitated by enhanced amphotericin B elimination through plasmapheresis. Positive outcomes were previously reported in two adult patients treated with plasmapheresis. However, other reports without plasmapheresis described fatal outcomes in adult patients, albeit with a twofold overdose compared to the two patients successfully treated with plasmapheresis. Moreover, plasmapheresis itself carries risks such as hypocalcemia, metabolic alkalosis, and coagulation deficits. Consequently, the role of plasmapheresis in amphotericin B overdose is still debated

Visual and personalized quality of life assessment app for people with severe mental health problems:Qualitative evaluation

Background:  QoL-ME is a digital visual personalized quality of life assessment app for people with severe mental health problems. Research reveals that e-mental health apps frequently suffer from low engagement and fall short of expectations regarding their impact on patients' daily lives. Studies often indicate that e-mental health apps ought to respect the needs and preferences of end users to achieve optimal user engagement. Objective:  The aim of this study was to explore the experiences of users regarding the usability and functionality of QoL-ME and whether the app is actionable and beneficial for patients. Methods:  End users (n=8) of QoL-ME contributed to semistructured interviews. An interview guide was used to direct the interviews. All interviews were audiorecorded and transcribed verbatim. Transcriptions were analyzed and coded thematically. Results:  Analysis revealed 3 main themes: (1) benefit, (2) actionability, and (3) characteristics of the QoL-ME. The first theme reveals that the QoL-ME app was beneficial for the majority of respondents, primarily by prompting them to reflect on their quality of life. The current version is not yet actionable; the actionability of the QoL-ME app may be improved by enabling users to view their scores over time and by supplying practical advice for quality of life improvements. Overall, participants had positive experiences with the usability, design, and content of the app. Conclusions:  The QoL-ME app can be beneficial to users as it provides them with insight into their quality of life and elicits reflection. Incorporating more functionalities that facilitate self-management, such as advice and strategies for improving areas that are lacking, will likely make the app actionable. Patients positively regarded the usability, design, and contents of the QoL-ME app

The ATPase activity of MLH1 is required to orchestrate DNA double-strand breaks and end processing during class switch recombination.

PublishedJournal ArticleResearch Support, N.I.H., ExtramuralResearch Support, Non-U.S. Gov'tAntibody diversification through somatic hypermutation (SHM) and class switch recombination (CSR) are similarly initiated in B cells with the generation of U:G mismatches by activation-induced cytidine deaminase but differ in their subsequent mutagenic consequences. Although SHM relies on the generation of nondeleterious point mutations, CSR depends on the production of DNA double-strand breaks (DSBs) and their adequate recombination through nonhomologous end joining (NHEJ). MLH1, an ATPase member of the mismatch repair (MMR) machinery, is emerging as a likely regulator of whether a U:G mismatch progresses toward mutation or DSB formation. We conducted experiments on cancer modeled ATPase-deficient MLH1G67R knockin mice to determine the function that the ATPase domain of MLH1 mediates in SHM and CSR. Mlh1(GR/GR) mice displayed a significant decrease in CSR, mainly attributed to a reduction in the generation of DSBs and diminished accumulation of 53BP1 at the immunoglobulin switch regions. However, SHM was normal in these mice, which distinguishes MLH1 from upstream members of the MMR pathway and suggests a very specific role of its ATPase-dependent functions during CSR. In addition, we show that the residual switching events still taking place in Mlh1(GR/GR) mice display unique features, suggesting a role for the ATPase activity of MLH1 beyond the activation of the endonuclease functions of its MMR partner PMS2. A preference for switch junctions with longer microhomologies in Mlh1(GR/GR) mice suggests that through its ATPase activity, MLH1 also has an impact in DNA end processing, favoring canonical NHEJ downstream of the DSB. Collectively, our study shows that the ATPase domain of MLH1 is important to transmit the CSR signaling cascade both upstream and downstream of the generation of DSBs.Spanish Ministry of Education and ScienceNIHNational Women’s Division of the Albert Einstein College of Medicin