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Objective The aim of this study is to describe recommendations made by clinical pharmacists when co-managing hypertension with physicians. Setting Two family medicine clinics at a major teaching hospital in the mid-western United States. Method This report details the specific recommendations made by pharmacists during a prospective randomized controlled clinical trial. Patients with uncontrolled hypertension were enrolled in a 9-month intensive pharmacist–physician co-management study. Clinical pharmacists saw patients at baseline, 2, 4, 6, and 8 month visits. Optional visits were allowed between required visits. Main outcome measure For this analysis, pharmacist recommendations were grouped. Physician acceptance of the pharmacists’ recommendations was also evaluated. Results Data from 101 patients were included and analyzed in this study. Changes in drug therapy were recommended 267 times for these 101 patients. Most recommendations for a change in treatment involved adding a new antihypertensive medication (46.4%) or increasing a dose (33.3%). The majority of pharmacist recommendations to modify drug therapy were made at the baseline visit (41.6%), with 76.8% of recommendations made by the 2 month visit. Physicians accepted and implemented 95.9% of the 267 pharmacist recommendations to modify drug therapy. Pharmacists recommended no change in the treatment plan 361 times, most often because the patient’s blood pressure (BP) had achieved the goal. Average BP decreased from 153.1 ± 10.0/84.9 ± 12.0 mmHg (average ± SD) at baseline to 124.2 ± 9.7/74.7 ± 9.6 mmHg ( P  < 0.001) at the end of 9 months, with 89.1% ( P  < 0.001) of patients reaching their BP goal. Conclusion Pharmacist recommendations for alterations in drug therapy generally occurred early in the course of the study and were largely to intensify therapy through higher dosages or additional medications. Pharmacist–physician co-management of BP is effective at reducing BP and improving BP control rates.

Ambulatory blood pressure monitoring (ABPM) is an accurate method for evaluating hypertension, yet its use in clinical practice may be limited by availability, cost, and patient inconvenience. The objective of this study was to investigate the ability of a 6-hour ABPM window to predict blood pressure control, based on that of the full 24-hour ABPM session across several clinical indications in a cohort of 486 patients referred for ABPM. Sensitivities and specificities of the 6-hour systolic blood pressure mean to accurately classify patients as hypertensive were determined using a fixed reference point of 130 mmHg for the 24-hour mean. For four common indications in which ABPM was ordered, prediction tables were constructed varying the thresholds for the 6-hour mean to find the optimal value that best predicted the 24-hour hypertensive status as determined from the full 24-hour interval. Using a threshold of 137 mmHg for the indications of borderline hypertension, evaluation of current antihypertensive regimen and suspected white-coat hypertension, sensitivity and specificity ranged from 0.83–0.88 and 0.80–0.88, respectively, for the ability of 6-hour ABPM to correctly categorize hypertensive status. Using 133 mmHg as the threshold for treatment resistance resulted in a sensitivity and specificity of 0.93 and 0.83, respectively. We conclude that a shortened ABPM session of 6 hours can be used to accurately classify blood pressure as controlled or not, based on the results of a 24-hour session. The optimal 6-hour threshold for comparison depends upon indication for referral.

This article outlines two theoretical and methodological approaches that take a queer intellectual curiosity about figurations of \"homosexuality\" and \"the homosexual\" as their core. These offer ways to conduct international relations (IR) research on \"the homosexual\" and on international relations figurations more broadly, for example, from \"the woman\" to \"the human rights holder.\" The first approach provides a method for analyzing figurations of \"the homosexual\" and sexualized orders of IR that are inscribed in IR as either normal or perverse. The second approach offers instructions on how to read plural figures and plural logics that signify as normal and/or perverse (and which might be described as queer). Together, they propose techniques, devices, and research questions to investigate singular and plural IR figurations—including but not exclusively those of \"the homosexual\"—that map international phenomena as diverse as colonialism, human rights, and the formation of states and international communities in ways that exceed IR survey research techniques that, for example, incorporate \"the homosexual\" into IR research through a \"sexuality variable.\"

What is queer? Why are queer international theories relevant to international relations? What might queer investigation of international relations look like? While debates about the meaning of the term 'queer' and whether or not queer can or ought to be defined rage on (Butler 1994; Warner 2012; Wilcox, this forum), many self-identified queer scholars cite Eve Kosofsky Sedgwick's description of queer as their point of departure. Sedgwick suggested that queer designates 'the open mesh of possibilities, gaps, overlaps, dissonances and resonances, lapses and excesses of meaning when the constituent elements of anyone's gender, of anyone's sexuality aren't made (or can't be made) to signify monolithically' (1993:8). Adapted from the source document.

The pathophysiology of dopamine dysregulation in schizophrenia involves alterations at the ventral midbrain level. Given that inflammatory mediators such as cytokines influence the functional properties of midbrain dopamine neurons, midbrain inflammation may play a role in schizophrenia by contributing to presynaptic dopamine abnormalities. Thus, we quantified inflammatory markers in dopaminergic areas of the midbrain of people with schizophrenia and matched controls. We also measured these markers in midbrain of mice exposed to maternal immune activation (MIA) during pregnancy, an established risk factor for schizophrenia and other psychiatric disorders. We found diagnostic increases in SERPINA3, TNFα, IL1β, IL6, and IL6ST transcripts in schizophrenia compared with controls (p < 0.02–0.001). The diagnostic differences in these immune markers were accounted for by a subgroup of schizophrenia cases (~ 45%, 13/28) showing high immune status. Consistent with the human cohort, we identified increased expression of immune markers in the midbrain of adult MIA offspring (SERPINA3, TNFα, and IL1β mRNAs, all p ≤ 0.01), which was driven by a subset of MIA offspring (~ 40%, 13/32) with high immune status. There were no diagnostic (human cohort) or group-wise (mouse cohort) differences in cellular markers indexing the density and/or morphology of microglia or astrocytes, but an increase in the transcription of microglial and astrocytic markers in schizophrenia cases and MIA offspring with high inflammation. These data demonstrate that immune-related changes in schizophrenia extend to dopaminergic areas of the midbrain and exist in the absence of changes in microglial cell number, but with putative evidence of microglial and astrocytic activation in the high immune subgroup. MIA may be one of the contributing factors underlying persistent neuroimmune changes in the midbrain of people with schizophrenia.

Little is known about the genetic basis of ecologically important morphological variation such as the diverse color patterns of mammals. Here we identify genetic changes contributing to an adaptive difference in color pattern between two subspecies of oldfield mice (Peromyscus polionotus). One mainland subspecies has a cryptic dark brown dorsal coat, while a younger beach-dwelling subspecies has a lighter coat produced by natural selection for camouflage on pale coastal sand dunes. Using genome-wide linkage mapping, we identified three chromosomal regions (two of major and one of minor effect) associated with differences in pigmentation traits. Two candidate genes, the melanocortin-1 receptor (Mc1r) and its antagonist, the Agouti signaling protein (Agouti), map to independent regions that together are responsible for most of the difference in pigmentation between subspecies. A derived mutation in the coding region of Mc1r, rather than change in its expression level, contributes to light pigmentation. Conversely, beach mice have a derived increase in Agouti mRNA expression but no changes in protein sequence. These two genes also interact epistatically: the phenotypic effects of Mc1r are visible only in genetic backgrounds containing the derived Agouti allele. These results demonstrate that cryptic coloration can be based largely on a few interacting genes of major effect.

Interactions between tumor cells and cancer-associated fibroblasts (CAFs) in the tumor microenvironment significantly influence cancer growth and metastasis. Transforming growth factor-β (TGF-β) is known to be a critical mediator of the CAF phenotype, and osteopontin (OPN) expression in tumors is associated with more aggressive phenotypes and poor patient outcomes. The potential link between these two pathways has not been previously addressed. Utilizing in vitro studies using human mesenchymal stem cells (MSCs) and MDA-MB231 (OPN+) and MCF7 (OPN−) human breast cancer cell lines, we demonstrate that OPN induces integrin-dependent MSC expression of TGF-β1 to mediate adoption of the CAF phenotype. This OPN–TGF-β1 pathway requires the transcription factor, myeloid zinc finger 1 (MZF1). In vivo studies with xenotransplant models in NOD-scid mice showed that OPN expression increases cancer growth and metastasis by mediating MSC-to-CAF transformation in a process that is MZF1 and TGF-β1 dependent. We conclude that tumor-derived OPN engenders MSC-to-CAF transformation in the microenvironment to promote tumor growth and metastasis via the OPN–MZF1–TGF-β1 pathway.

 From Samuel Huntington's highly controversial Who Are We? to the urgent appeal of Naomi Wolf's The End of America, Americans are increasingly reflecting on questions of democracy, multiculturalism, and national identity. Yet such debates take place largely at the level of elites, leaving out ordinary American citizens, who have much to offer about the lived reality behind the phrase, \"I am an American.\"   Cynthia Weber set out on a journey across post-9/11 America in search of a deeper understanding of what it means to be an American today. The result is this brave and captivating memoir that gives a voice to ordinary citizens for whom the terrorist attacks of 2001—and their lingering aftermath—live on in collective memory. Heartrending first-person testimonials reveal how the ongoing fear of terrorists and immigrants has betrayed America's core values of fairness and equality, which have been further weakened by polarizing international and domestic responses. Considered together, these portraits also provide a sharp contrast to the idealized vision of Americanness frequently spun by media and politicians.   Far more than a mere remembrance book about September 11, 'I am an American' offers precisely the kind of ground-level empathy needed to reignite a meaningful national debate about who we are and who we might become as a people and a nation.

The process was coordinated by the World Health Organization. * Forty-five leading childhood pneumonia researchers suggested more than 500 research ideas, which were merged into 158 research questions that spanned the broad spectrum of epidemiological research, health policy and systems research, improvement of existing interventions, and development of new interventions. * Within the short time frame in which gains were expected globally, the research priorities were dominated by health systems and policy research topics (e.g., studying barriers to health care seeking and access, as well as barriers to increased coverage with available vaccines; and evaluating the potential to safely scale up antibiotic treatment through community health workers). * These were followed by epidemiological questions to identify the main gaps in knowledge (e.g., predictors of severe pneumonia that requires hospitalisation); priorities for improvement of the existing interventions (e.g., training of community health workers to recognise danger signs, refer, and treat sick children); and identifying cost reduction mechanisms for the available conjugate vaccines. * Among the new interventions, the greatest support was shown for the development of low-cost conjugate vaccines and cross-protective common protein vaccines against the pneumococcus. Furthermore, pneumonia is recognised as a common and serious consequence of pandemic influenza, and preparedness for pandemic influenza should include prevention and control of pneumonia [11].\\n Dowell (Centers for Disease Control and Prevention, Atlanta, Georgia, United States of America), Michael English (KEMRI/Wellcome Trust Research Programme, Nairobi, Kenya), Adegoke G. Falade (Department of Pediatrics, College of Medicine, University of Ibadan, Ibadan, Nigeria), Brian Greenwood (Department of Infectious & Tropical Diseases, London School of Hygiene and Tropical Medicine, London, United Kingdom), Rana Hajjeh (Centers for Disease Control and Prevention, Atlanta, Georgia, United States of America), Tabish Hazir (Children's Hospital, Pakistan Institute of Medical Sciences, Islamabad, Pakistan), Patricia Hibberd (Division of Global Health, Department of Pediatrics, Massachussetts General Hospital, Boston, Massachusetts, United States of America), Stephen Howie (MRC Laboratories, Fajara, Banjul, The Gambia), Prakash M. Jeena (Department of Paediatrics and Child Health, Nelson R. Mandela School of Medicine, University of Natal, Durban, South Africa), Karin Kallander (Department of Public Health Sciences, Karolinska Institutet, Stockholm, Sweden), Keith Klugman (Hubert Department of Global Health, The Rollins School of Public Health, Emory University, Atlanta, Georgia, United States of America), Shabir Madhi (Respiratory and Meningeal Pathogens Research Unit, Chris Hani - Baragwanath Hospital, Bertsham Gauteng, South Africa), Kim Mulholland (Department of Infectious & Tropical Diseases, London School of Hygiene and Tropical Medicine, London, United Kingdom), Stephen K. Obaro (Children's Hospital of Pittsburgh, Pittsburgh, Pennsylvania, United States of America), Stefan Peterson (Department of Public Health Sciences, Karolinska Institutet, Stockholm, Sweden), Zeba Rasmussen (Division of International Epidemiology and Population Studies, Fogarty International Center, National Institutes of Health, Bethesda, Maryland, United States of America), Anna Roca (University of Barcelona, Barcelona, Spain), H. P. S. Sachdev (Sitaram Bhartia Institute of Science and Research, New Delhi, India), Mathuram Santosham (Department of International Health, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, United States of America), Anne Schuchat (Centers for Disease Control and Prevention, Atlanta, Georgia, United States of America), Donald M. Thea (Center for International Health, Boston University School of Public Health, Boston, Massachusetts, United States of America), and Paul Torzillo (R.P.A. Medical Centre, University of Sydney, Sydney, Australia).

Stefan Pfister and the ICGC PedBrain Tumor Project report whole-genome sequencing of 96 pilocytic astrocytomas. They identify recurrent activating mutations in FGFR1 and PTPN11 and novel NTRK2 fusion genes. Pilocytic astrocytoma, the most common childhood brain tumor 1 , is typically associated with mitogen-activated protein kinase (MAPK) pathway alterations 2 . Surgically inaccessible midline tumors are therapeutically challenging, showing sustained tendency for progression 3 and often becoming a chronic disease with substantial morbidities 4 . Here we describe whole-genome sequencing of 96 pilocytic astrocytomas, with matched RNA sequencing ( n = 73), conducted by the International Cancer Genome Consortium (ICGC) PedBrain Tumor Project. We identified recurrent activating mutations in FGFR1 and PTPN11 and new NTRK2 fusion genes in non-cerebellar tumors. New BRAF -activating changes were also observed. MAPK pathway alterations affected all tumors analyzed, with no other significant mutations identified, indicating that pilocytic astrocytoma is predominantly a single-pathway disease. Notably, we identified the same FGFR1 mutations in a subset of H3F3A -mutated pediatric glioblastoma with additional alterations in the NF1 gene 5 . Our findings thus identify new potential therapeutic targets in distinct subsets of pilocytic astrocytoma and childhood glioblastoma.