Virtual signatures of dark sectors in Higgs couplings

Where collider searches for resonant invisible particles loose steam, dark sectors might leave their trace as virtual effects in precision observables. Here we explore this option in the framework of Higgs portal models, where a sector of dark fermions interacts with the standard model through a strong renormalizable coupling to the Higgs boson. We show that precise measurements of Higgs-gauge and triple Higgs interactions can probe dark fermions up to the TeV scale through virtual corrections. Observation prospects at the LHC and future lepton colliders are discussed for the so-called singlet-doublet model of Majorana fermions, a generalization of the bino-higgsino scenario in supersymmetry. We advocate a two-fold search strategy for dark sectors through direct and indirect observables.Comment: 20 pages, 7 figures, 1 tabl

Localized practices and globalized futures: challenges for Alaska coastal community youth

An article from Maritime Studies (2015) 14:

Reasons for accepting or declining to participate in randomized clinical trials for cancer therapy

This paper reports on the reasons why patients agreed to or declined entry into randomized trials of cancer following discussions conducted by clinicians in both District General and University Hospitals. Two hundred and four patients completed a 16-item questionnaire following the consultation, of these 112 (55%) were women with breast cancer. Overall results showed that 147 (72.1%) patients accepted entry to a randomized clinical trial (RCT). The main reasons nominated for participating in a trial were that ‘others will benefit’ (23.1%) and ‘trust in the doctor’ (21.1%). One of the main reasons for declining trial entry was that patients were ‘worried about randomization’ (19.6%). There was a significantly higher acceptance rate for trials providing active treatment in every arm 98 (80.6%) compared with those trials with a no treatment arm 46 (60.5%), χ2test P = 0.003. The study outlines a number of factors that appear to influence a patient’s decision to accept or decline entry into an RCT of cancer therapy. An important factor is whether or not the trial offers active treatment in all arms of the study. Communication that promotes trust and confidence in the doctor is also a powerful motivating influence. © 2000 Cancer Research Campaig

cAMP-Signalling Regulates Gametocyte-Infected Erythrocyte Deformability Required for Malaria Parasite Transmission.

Blocking Plasmodium falciparum transmission to mosquitoes has been designated a strategic objective in the global agenda of malaria elimination. Transmission is ensured by gametocyte-infected erythrocytes (GIE) that sequester in the bone marrow and at maturation are released into peripheral blood from where they are taken up during a mosquito blood meal. Release into the blood circulation is accompanied by an increase in GIE deformability that allows them to pass through the spleen. Here, we used a microsphere matrix to mimic splenic filtration and investigated the role of cAMP-signalling in regulating GIE deformability. We demonstrated that mature GIE deformability is dependent on reduced cAMP-signalling and on increased phosphodiesterase expression in stage V gametocytes, and that parasite cAMP-dependent kinase activity contributes to the stiffness of immature gametocytes. Importantly, pharmacological agents that raise cAMP levels in transmissible stage V gametocytes render them less deformable and hence less likely to circulate through the spleen. Therefore, phosphodiesterase inhibitors that raise cAMP levels in P. falciparum infected erythrocytes, such as sildenafil, represent new candidate drugs to block transmission of malaria parasites

Contribution of Cystine-Glutamate Antiporters to the Psychotomimetic Effects of Phencyclidine

Altered glutamate signaling contributes to a myriad of neural disorders, including schizophrenia. While synaptic levels are intensely studied, nonvesicular release mechanisms, including cystine–glutamate exchange, maintain high steady-state glutamate levels in the extrasynaptic space. The existence of extrasynaptic receptors, including metabotropic group II glutamate receptors (mGluR), pose nonvesicular release mechanisms as unrecognized targets capable of contributing to pathological glutamate signaling. We tested the hypothesis that activation of cystine–glutamate antiporters using the cysteine prodrug N-acetylcysteine would blunt psychotomimetic effects in the rodent phencyclidine (PCP) model of schizophrenia. First, we demonstrate that PCP elevates extracellular glutamate in the prefrontal cortex, an effect that is blocked by N-acetylcysteine pretreatment. To determine the relevance of the above finding, we assessed social interaction and found that N-acetylcysteine reverses social withdrawal produced by repeated PCP. In a separate paradigm, acute PCP resulted in working memory deficits assessed using a discrete trial t-maze task, and this effect was also reversed by N-acetylcysteine pretreatment. The capacity of N-acetylcysteine to restore working memory was blocked by infusion of the cystine–glutamate antiporter inhibitor (S)-4-carboxyphenylglycine into the prefrontal cortex or systemic administration of the group II mGluR antagonist LY341495 indicating that the effects of N-acetylcysteine requires cystine–glutamate exchange and group II mGluR activation. Finally, protein levels from postmortem tissue obtained from schizophrenic patients revealed significant changes in the level of xCT, the active subunit for cystine–glutamate exchange, in the dorsolateral prefrontal cortex. These data advance cystine–glutamate antiporters as novel targets capable of reversing the psychotomimetic effects of PCP

Development of a Standardized Screening Rule for Tuberculosis in People Living with HIV in Resource-Constrained Settings: Individual Participant Data Meta-analysis of Observational Studies

Haileyesus Getahun and colleagues report the development of a simple, standardized tuberculosis (TB) screening rule for resource-constrained settings, to identify people living with HIV who need further investigation for TB disease

Pulmonary tuberculosis among people living with HIV/AIDS attending care and treatment in rural northern Tanzania

Tuberculosis is the commonest opportunistic infection and the number one cause of death in HIV/AIDS patients in developing countries. To address the extent of the tuberculosis HIV coinfection in rural Tanzania we conducted a cross sectional study including HIV/AIDS patients attending care and treatment clinic from September 2006 to March 2007. Sputum samples were collected for microscopy, culture and drug susceptibility testing. Chest X-ray was done for those patients who consented. Blood samples were collected for CD4+ T cells count. The prevalence of tuberculosis was 20/233 (8.5%). Twenty (8.5%) sputum samples were culture positive. Eight of the culture positive samples (40%) were smear positive. Fifteen (75%) of these patients neither had clinical symptoms nor chest X-ray findings suggestive of tuberculosis. Nineteen isolates (95%) were susceptible to rifampicin, isoniazid, streptomycin and ethambutol (the first line tuberculosis drugs). One isolate (5%) from HIV/tuberculosis coinfected patients was resistant to isoniazid. No cases of multi- drug resistant tuberculosis were identified. We found high prevalence of tuberculosis disease in this setting. Chest radiograph suggestive of tuberculosis and clinical symptoms of fever and cough were uncommon findings in HIV/tuberculosis coinfected patients. Tuberculosis can occur at any stage of CD4+T cells depletion

Ready or not? Expectations of faculty and medical students for clinical skills preparation for clerkships

Background: Preclerkship clinical-skills training has received increasing attention as a foundational preparation for clerkships. Expectations among medical students and faculty regarding the clinical skills and level of skill mastery needed for starting clerkships are unknown. Medical students, faculty teaching in the preclinical setting, and clinical clerkship faculty may have differing expectations of students entering clerkships. If students' expectations differ from faculty expectations, students may experience anxiety. Alternately, congruent expectations among students and faculty may facilitate integrated and seamless student transitions to clerkships. Aims: To assess the congruence of expectations among preclerkship faculty, clerkship faculty, and medical students for the clinical skills and appropriate level of clinical-skills preparation needed to begin clerkships. Methods: Investigators surveyed preclinical faculty, clerkship faculty, and medical students early in their basic clerkships at a North American medical school that focuses on preclerkship clinical-skills development. Survey questions assessed expectations for the appropriate level of preparation in basic and advanced clinical skills for students entering clerkships. Results: Preclinical faculty and students had higher expectations than clerkship faculty for degree of preparation in most basic skills. Students had higher expectations than both faculty groups for advanced skills preparation. Conclusions: Preclinical faculty, clerkship faculty, and medical students appear to have different expectations of clinical-skills training needed for clerkships. As American medical schools increasingly introduce clinical-skills training prior to clerkships, more attention to alignment, communication, and integration between preclinical and clerkship faculty will be important to establish common curricular agendas and increase integration of student learning. Clarification of skills expectations may also alleviate student anxiety about clerkships and enhance their learning