Cluster-randomized, crossover trial of head positioning in acute stroke

The role of supine positioning after acute stroke in improving cerebral blood flow and the countervailing risk of aspiration pneumonia have led to variation in head positioning in clinical practice. We wanted to determine whether outcomes in patients with acute ischemic stroke could be improved by positioning the patient to be lying flat (i.e., fully supine with the back horizontal and the face upwards) during treatment to increase cerebral perfusion. METHODS In a pragmatic, cluster-randomized, crossover trial conducted in nine countries, we assigned 11,093 patients with acute stroke (85% of the strokes were ischemic) to receive care in either a lying-flat position or a sitting-up position with the head elevated to at least 30 degrees, according to the randomization assignment of the hospital to which they were admitted; the designated position was initiated soon after hospital admission and was maintained for 24 hours. The primary outcome was degree of disability at 90 days, as assessed with the use of the modified Rankin scale (scores range from 0 to 6, with higher scores indicating greater disability and a score of 6 indicating death). RESULTS The median interval between the onset of stroke symptoms and the initiation of the assigned position was 14 hours (interquartile range, 5 to 35). Patients in the lying-flat group were less likely than patients in the sitting-up group to maintain the position for 24 hours (87% vs. 95%, P\u3c0.001). In a proportional-odds model, there was no significant shift in the distribution of 90-day disability outcomes on the global modified Rankin scale between patients in the lying-flat group and patients in the sitting-up group (unadjusted odds ratio for a difference in the distribution of scores on the modified Rankin scale in the lying-flat group, 1.01; 95% confidence interval, 0.92 to 1.10; P = 0.84). Mortality within 90 days was 7.3% among the patients in the lying-flat group and 7.4% among the patients in the sitting-up group (P = 0.83). There were no significant betweengroup differences in the rates of serious adverse events, including pneumonia. CONCLUSIONS Disability outcomes after acute stroke did not differ significantly between patients assigned to a lying-flat position for 24 hours and patients assigned to a sitting-up position with the head elevated to at least 30 degrees for 24 hours

The effects of patent harmonization on inventors

Thesis (M.S.)--Massachusetts Institute of Technology, Dept. of Mechanical Engineering, 1994.by Lily Lim.M.S

Conflicts of Interest in Sell-side Research and The Moderating Role of Institutional Investors

Because sell-side analysts are dependent on institutional investors for performance ratings and trading commissions, we argue that analysts are less likely to succumb to investment banking or brokerage pressure in stocks highly visible to institutional investors. Examining a comprehensive sample of analyst recommendations over the 1994-2000 period, we find that analysts’ recommendations relative to consensus are positively associated with investment banking relationships and brokerage pressure, but negatively associated with the presence of institutional investor owners. The presence of institutional investors is also associated with more accurate earnings forecasts and more timely re-ratings following severe share price falls

The function and evolution of the restriction factor viperin in primates was not driven by lentiviruses

Abstract Background Viperin, also known as RSAD2, is an interferon-inducible protein that potently restricts a broad range of different viruses such as influenza, hepatitis C virus, human cytomegalovirus and West Nile virus. Viperin is thought to affect virus budding by modification of the lipid environment within the cell. Since HIV-1 and other retroviruses depend on lipid domains of the host cell for budding and infectivity, we investigated the possibility that Viperin also restricts human immunodeficiency virus and other retroviruses. Results Like other host restriction factors that have a broad antiviral range, we find that viperin has also been evolving under positive selection in primates. The pattern of positive selection is indicative of Viperin's escape from multiple viral antagonists over the course of primate evolution. Furthermore, we find that Viperin is interferon-induced in HIV primary target cells. We show that exogenous expression of Viperin restricts the LAI strain of HIV-1 at the stage of virus release from the cell. Nonetheless, the effect of Viperin restriction is highly strain-specific and does not affect most HIV-1 strains or other retroviruses tested. Moreover, knockdown of endogenous Viperin in a lymphocytic cell line did not significantly affect the spreading infection of HIV-1. Conclusion Despite positive selection having acted on Viperin throughout primate evolution, our findings indicate that Viperin is not a major restriction factor against HIV-1 and other retroviruses. Therefore, other viral lineages are likely responsible for the evolutionary signatures of positive selection in viperin among primates.</p

Regulation of DNA damage responses and cell cycle progression by hMOB2.

Mps one binder proteins (MOBs) are conserved regulators of essential signalling pathways. Biochemically, human MOB2 (hMOB2) can inhibit NDR kinases by competing with hMOB1 for binding to NDRs. However, biological roles of hMOB2 have remained enigmatic. Here, we describe novel functions of hMOB2 in the DNA damage response (DDR) and cell cycle regulation. hMOB2 promotes DDR signalling, cell survival and cell cycle arrest after exogenously induced DNA damage. Under normal growth conditions in the absence of exogenously induced DNA damage hMOB2 plays a role in preventing the accumulation of endogenous DNA damage and a subsequent p53/p21-dependent G1/S cell cycle arrest. Unexpectedly, these molecular and cellular phenotypes are not observed upon NDR manipulations, indicating that hMOB2 performs these functions independent of NDR signalling. Thus, to gain mechanistic insight, we screened for novel binding partners of hMOB2, revealing that hMOB2 interacts with RAD50, facilitating the recruitment of the MRE11-RAD50-NBS1 (MRN) DNA damage sensor complex and activated ATM to DNA damaged chromatin. Taken together, we conclude that hMOB2 supports the DDR and cell cycle progression

Relative Efficacy of AS03-Adjuvanted Pandemic Influenza A(H1N1) Vaccine in Children: Results of a Controlled, Randomized Efficacy Trial

Background. the vaccine efficacy (VE) of 1 or 2 doses of AS03-adjuvanted influenza A(H1N1) vaccine relative to that of 2 doses of nonadjuvanted influenza A(H1N1) vaccine in children 6 months to <10 years of age in a multinational study conducted during 2010-2011.Methods. A total of 6145 children were randomly assigned at a ratio of 1: 1: 1 to receive 2 injections 21 days apart of A/California/7/2009(H1N1)-AS03 vaccine at dose 1 and saline placebo at dose 2, 2 doses 21 days apart of A/California/7/2009(H1N1)-AS03 vaccine (the Ad2 group), or 2 doses 21 days apart of nonadjuvanted A/California/7/2009(H1N1) vaccine (the NAd2 group). Active surveillance for influenza-like illnesses continued from days 14 to 385. Nose and throat samples obtained during influenza-like illnesses were tested for A/California/7/2009 (H1N1), using reverse-transcriptase polymerase chain reaction. Immunogenicity, reactogenicity, and safety were assessed.Results. There were 23 cases of confirmed 2009 pandemic influenza A(H1N1) (A[H1N1]pdm09) infection for the primary relative VE analysis. the VE in the Ad2 group relative to that in the NAd2 group was 76.8% (95% confidence interval, 18.5%-93.4%). the benefit of the AS03 adjuvant was demonstrated in terms of the greater immunogenicity observed in the Ad2 group, compared with the NAd2 group.Conclusion. the 4-8-fold antigen-sparing adjuvanted pandemic influenza vaccine demonstrated superior and clinically important prevention of A(H1N1)pdm09 infection, compared with nonadjuvanted vaccine, with no observed increase in medically attended or serious adverse events. These data support the use of adjuvanted influenza vaccines during influenza pandemics.GlaxoSmithKline BiologicalsUniv Melbourne, Murdoch Childrens Res Inst, Carlton, Vic 3010, AustraliaUniv Melbourne, Melbourne Sch Populat & Global Hlth, Carlton, Vic 3010, AustraliaGlaxoSmithKline Vaccines, King of Prussia, PA USANovavax, Rockville, MD USAMary Chiles Gen Hosp, Dept Pediat, Manila, PhilippinesDe La Salle Hlth Sci Inst, Dept Pediat, Dasmarinas City, PhilippinesRes Inst Trop Med, Dept Hlth, Muntinlupa, PhilippinesUniversidade Federal de São Paulo, Dept Pediat, São Paulo, BrazilFac Ciencias Med Santa Casa São Paulo, Dept Pediat, São Paulo, BrazilAssoc Fundo Incent Pesquisa, São Paulo, BrazilInst Costarricense Invest Clin, San Jose, Costa RicaNatl Inst Publ Hlth Mexico, Cuernavaca, Morelos, MexicoUniv Autonoma Nuevo Leon, Serv Med, Monterrey, MexicoInst Nacl Pediat Mexico, Mexico City, DF, MexicoHosp Gen Durango, Durango, MexicoPhramongkutklao Hosp, Infect Dis Unit, Dept Pediat, Bangkok, ThailandKhon Kaen Univ, Dept Pediat, Fac Med, Khon Kaen, ThailandNatl Healthcare Grp Polyclin, Singapore, SingaporeCtr Estudios Infect Pediat, Cali, ColombiaGlaxoSmithKline Vaccines, Wavre, BelgiumGlaxoSmithKline Vaccines, Rixensart, BelgiumUniversidade Federal de São Paulo, Dept Pediat, São Paulo, BrazilWeb of Scienc

The immunological landscape of traumatic brain injury: insights from pathophysiology to experimental models

Traumatic brain injury (TBI) is a complex, heterogeneous neuropathological disease that continues to be among the prominent causes of mortality and disability around the world. Translational success in TBI has been significant, yet therapies are limited as the intersection of the initial mechanical traumas and secondary neuroinflammatory cascades, which predispose to long-term neurological deficits, is poorly understood. The pathogenesis of TBI is not limited to the primary mechanical injury. The secondary damage, including ischemia, excitotoxicity, oxidative stress, and immune dysfunction, leads to neuronal apoptosis, the breakdown of the blood–brain barrier (BBB), and chronic neuroinflammation. The preclinical controlled cortical impact (CCI) and fluid percussion injury (FPI) TBI models have generated valuable biomechanical data related to TBI-induced immune responses, including microglial priming, astrocyte dysregulation, and peripheral leukocyte recruitment. However, experimental models today are unable to completely replicate the intricate immune cascades in human TBI, particularly delayed and context-specific innate and adaptive immune response activation. Cytokine signaling (IL-1β, TNF-α, and IL-6), neuroinflammatory amplification through the IL-23/IL-17 pathway, and autoantibody-mediated neurodegeneration are emerging as significant secondary injury mechanisms. Additionally, TBI-induced immunosuppression, which presents as generalized T lymphocyte depletion and aberrant macrophage polarization, enhances the risk of infection and delayed neurological recovery. Emerging immunotherapeutics such as cytokine blockade, complement blockade, and targeted modulation of T lymphocytes have the potential to optimize the post-TBI immune microenvironment for reducing secondary damage. Inclusion of next-generation experimental models combined with secondary injuries, such as hypoxia, polytrauma, and systemic inflammation, is needed to shift towards innovative, biomarker-driven, patient-stratified trials. Thus, integration of immunological phenotyping with translationally relevant models of TBI represents an important cornerstone in the development of targeted therapeutic treatments designed to improve neuroprotection, repair, and long-term functional outcome

Neither thermosonication nor cold sonication is better than pasteurization for milk shelf life

High-power, low-frequency ultrasound has been suggested as a novel processing technique with the potential to extend milk shelf life via inactivation of bacteria and spores that survive standard pasteurization. The primary objective of this research was to determine whether short-duration (≤60 s) sonication treatment, in conjunction with pasteurization, can increase shelf life while producing no adverse aroma effect. Skim milk was inoculated with Paenibacillus amylolyticus, a spore-forming, thermotolerant and psychrophilic milk contamination bacterium. Milk was sonicated under 6 selected amplitude and time conditions, except for control. Both cold sonicated (C-S) and thermosonicated (T-S) milk and milk treatments were pasteurized; however, T-S milk was sonicated after pasteurization (72.5 ± 0.3°C; mean ± SD), whereas C-S milk was sonicated at 12.5 ± 5°C (mean ± SD) before pasteurization. Milk was refrigerated up to 50 d and total aerobic counts were enumerated on pasteurized control, C-S, and T-S milk weekly. Neither C-S nor T-S treatments reduced total aerobic counts to an equivalent level as pasteurization alone. Counts in pasteurized controls and C-S milk did not exceed 3.00 log cfu/mL for up to 50 d; counts in T-S milk exceeded 5.00 cfu/mL by d 36. Aroma qualities (cooked, lacks freshness, and rubbery) of 2 T-S treatment intensities [170 µm peak-to-peak (p-p) for 60s and 200 µmp-p for 10 s] and pasteurized controls were evaluated by a trained descriptive sensory panel. No significant differences were observed in cooked or lacks freshness aromas among samples. Only the milk treated with 170 µmp-p for 60 s had significantly higher rubbery aroma on d 1 compared with milk treated with 200 µmp-p for 10 s. Although the sensory effects of T-S on milk may not limit the commercial feasibility of cold sonication or thermosonication, conditions that differ from those used in the present study should be considered in the future. Neither C-S nor T-S were appropriate techniques for reducing bacterial count in fluid milk beyond standard pasteurization and, in fact, increased counts of spore-forming spoilage bacteria

Enrollment and attendance to Cardiac Rehabilitation after Percutaneous Coronary Intervention in Sarawak : A Prospective Study

Abstract: Background: Cardiac rehabilitation is vital for cardiac patients, especially after the percutaneous coronary intervention as it is proven to reduce recurrent cardiac event and death. The ongoing CR participations of the patients in Sarawak after percutaneous coronary intervention have not been explored. Purpose: To examine the enrollment and attendance to cardiac rehabilitation among patients who have underwent percutaneous coronary intervention in Sarawak. Methods: A prospective study was conducted. Data on baseline characteristics, diagnosis, smoking status, and referrals received for CR were collected for selected subjects prior to hospital discharge. Their attendances to CR programme were followed up at two months after hospital discharge. Independent sample Ttest was used to analyse the continuous data and Chi square test was conducted for categorical data to identify the differences in characteristics between patients who was enrolled for CR and those who was not. Results: Three hundred and eighty patients were recruited in this study. Among these patients, 141 patients (37.11%) were referred to CR. Only 58 patients (15.3%) completed all the eight sessions of the CR programme, 276 patients (72.6%) did not turn up and 46 patients (12.1%) dropped out before completing all the sessions. Patients who were enrolled in CR were more likely to be men (p=0.001), Malay (p=0.000), having travel time of less than 1 hour from home to hospital (p=0.000), and able to drive (p=0.009). Conclusions/ Implications for Practice: The enrollment and attendance rate of CR in Sarawak is low. Men, Malay, staying near to the hospital, and being a driver were more likely to be referred to CR. Further study on this is needed as CR is proven to benefit the patients