Standardizing America: Why it Should Be a Method of the Past

This paper examines, critiques, and suggests improvements on the method of standardized testing in American schools. This paper discusses the history and development of standardized testing and its initial purpose and intentions. Additionally, the effects of standardized testing on students, teachers, and parents are evaluated, with special consideration on how high stakes testing adversely affects disadvantaged student groups such as children in minorities and low-income districts, bilingual students, and children with disabilities. The research suggests that standardized testing is not only damaging to students in these groups, but most likely not the most efficient way of testing student performance in any circumstance. The negative effects that teachers, students, and parents face during times of high stakes testing create an unnerving environment that can cause inaccurate results. Furthermore, the inaccurate results leading to poor performance then takes a toll on low-income districts even more. Districts with students who perform well receive more funding, programs, and resources as a ‘reward’, while districts with poor performance receive nothing, only exaggerating the gap in resource wealth. This research concludes with suggestions and alternatives to standardized testing that may better serve the American educational system as a whole. Programs such as sample testing, stealth assessments, and additional measures of assessment without a testing environment may not only provide a better and more accurate reading, but also create a more inclusive, healthier learning atmosphere. The research provided in this essay, in conjuncture with additional studies and information, could help push policy reform in the American education system for the better

Uneven distribution of cobamide biosynthesis and dependence in bacteria predicted by comparative genomics.

The vitamin B12 family of cofactors known as cobamides are essential for a variety of microbial metabolisms. We used comparative genomics of 11,000 bacterial species to analyze the extent and distribution of cobamide production and use across bacteria. We find that 86% of bacteria in this data set have at least one of 15 cobamide-dependent enzyme families, but only 37% are predicted to synthesize cobamides de novo. The distribution of cobamide biosynthesis and use vary at the phylum level. While 57% of Actinobacteria are predicted to biosynthesize cobamides, only 0.6% of Bacteroidetes have the complete pathway, yet 96% of species in this phylum have cobamide-dependent enzymes. The form of cobamide produced by the bacteria could be predicted for 58% of cobamide-producing species, based on the presence of signature lower ligand biosynthesis and attachment genes. Our predictions also revealed that 17% of bacteria have partial biosynthetic pathways, yet have the potential to salvage cobamide precursors. Bacteria with a partial cobamide biosynthesis pathway include those in a newly defined, experimentally verified category of bacteria lacking the first step in the biosynthesis pathway. These predictions highlight the importance of cobamide and cobamide precursor salvaging as examples of nutritional dependencies in bacteria

Beneficial pleiotropic antidepressive effects of cardiovascular disease risk factor interventions in the metabolic syndrome

© 2018 The Authors. Background--Although the increased prevalence and severity of clinical depression and elevated cardiovascular disease risk represent 2 vexing public health issues, the growing awareness of their combined presentation compounds the challenge. The obese Zucker rat, a model of the metabolic syndrome, spontaneously develops significant depressive symptoms in parallel with the progression of the metabolic syndrome and, thus, represents a compelling model for study. The primary objective was to assess the impact on both cardiovascular outcomes, specifically vascular structure and function, and depressive symptoms in obese Zucker rats after aggressive treatment for cardiovascular disease risk factors with long-term exercise or targeted pharmacological interventions. Methods and Results--We chronically treated obese Zucker rats with clinically relevant interventions against cardiovascular disease risk factors to determine impacts on vascular outcomes and depressive symptom severity. While most of the interventions (chronic exercise, anti-hypertensive, the interventions (long-term exercise, antihypertensive, antidyslipidemia, and antidiabetic) were differentially effective at improving vascular outcomes, only those that also resulted in a significant improvement to oxidant stress, inflammation, arachidonic acid metabolism (prostacyclin versus thromboxane A2), and their associated sequelae were effective at also blunting depressive symptom severity. Using multivariable analyses, discrimination between the effectiveness of treatment groups to maintain behavioral outcomes appeared to be dependent on breaking the cycle of inflammation and oxidant stress, with the associated outcomes of improving endothelial metabolism and both cerebral and peripheral vascular structure and function. Conclusions--This initial study provides a compelling framework from which to further interrogate the links between cardiovascular disease risk factors and depressive symptoms and suggests mechanistic links and potentially effective avenues for intervention

The incidence and make up of ability grouped sets in the UK primary school

The adoption of setting in the primary school (pupils ability grouped across classes for particular subjects) emerged during the 1990s as a means to raise standards. Recent research based on 8875 children in the Millennium Cohort Study showed that 25.8% of children in Year 2 were set for literacy and mathematics and a further 11.2% of children were set for mathematics or literacy alone. Logistic regression analysis showed that the best predictors of being in the top set for literacy or mathematics were whether the child was born in the Autumn or Winter and cognitive ability scores. Boys were significantly more likely than girls to be in the bottom literacy set. Family circumstances held less importance for setting placement compared with the child’s own characteristics, although they were more important in relation to bottom set placement. Children in bottom sets were significantly more likely to be part of a long-term single parent household, have experienced poverty, and not to have a mother with qualifications at NVQ3 or higher levels. The findings are discussed in relation to earlier research and the implications for schools are set out

Desmopressin for bleeding in non-severe hemophilia A:Suboptimal use in a real-world setting

Background Desmopressin is an important treatment option in nonsevere hemophilia A because it has several benefits compared with factor (F) concentrates, including no inhibitor risk and much lower costs. Despite these advantages, data are limited on the real-world use of desmopressin in the treatment of bleeds. Objective To describe the clinical use of desmopressin in relation to other therapeutic modalities in the treatment of bleeding episodes in patients with nonsevere hemophilia A. Methods Patients with nonsevere hemophilia A aged 12-55 years were included from the DYNAMO cohort study. Data on the desmopressin test response and treated bleeding events in the period January 2009 to July 2020 were retrospectively collected from medical files. An adequate desmopressin test response was defined based on a peak FVIII level of >= 30 IU/dl. Results A total of 248 patients with a median age of 38 years (interquartile range 25-49) were included. An adequate desmopressin test response was documented in 25% and 73% of patients with moderate and mild hemophilia, respectively. In adequate responders, 51% of bleeds were exclusively treated with FVIII concentrates, 24% exclusively with desmopressin, 21% with a combination of both and 4% with other treatments. In 54% of bleeds treated with a single dose of factor concentrates, the expected FVIII level after desmopressin exceeded the level targeted. Conclusion Most bleeds in patients with an adequate response to desmopressin are treated with factor concentrates. These findings may indicate a suboptimal use of desmopressin and that barriers to the use of desmopressin should be explored.Thrombosis and Hemostasi

A Student\u27s Guide to giant Viruses Infecting Small Eukaryotes: From Acanthamoeba to Zooxanthellae

The discovery of infectious particles that challenge conventional thoughts concerning “what is a virus” has led to the evolution a new field of study in the past decade. Here, we review knowledge and information concerning “giant viruses”, with a focus not only on some of the best studied systems, but also provide an effort to illuminate systems yet to be better resolved. We conclude by demonstrating that there is an abundance of new host–virus systems that fall into this “giant” category, demonstrating that this field of inquiry presents great opportunities for future research

Standards of conduct and reporting in evidence syntheses that could inform environmental policy and management decisions

Accurate, unbiased and concise synthesis of available evidence following clear methodology and transparent report‑ ing is necessary to support effective environmental policy and management decisions. Without this, less reliable and/ or less objective reviews of evidence could inform decision making, leading to ineffective, resource wasteful inter‑ ventions with potential for unintended consequences. We evaluated the reliability of over 1000 evidence syntheses (reviews and overviews) published between 2018 and 2020 that provide evidence on the impacts of human activities or effectiveness of interventions relevant to environmental management. The syntheses are drawn from the Col‑ laboration for Environmental Evidence Database of Evidence Reviews (CEEDER), an online, freely available evidence service for evidence users that assesses the reliability of evidence syntheses using a series of published criteria. We found that the majority of syntheses have problems with transparency, replicability and potential for bias. Overall, our results suggest that most recently published evidence syntheses are of low reliability to inform decision making. Reviews that followed guidance and reporting standards for evidence synthesis had improved assessment ratings, but there remains substantial variation in the standard of reviews amongst even these. Furthermore, the term ‘system‑ atic review’, which implies conformity with a methodological standard, was frequently misused. A major objective of the CEEDER project is to improve the reliability of the global body of environmental evidence reviews. To this end we outline freely available online resources to help improve review conduct and reporting. We call on authors, editors and peer reviewers to use these resources to ensure more reliable syntheses in the future

Modified Pilates as an adjunct to standardphysiotherapy care for urinaryincontinence: a mixed methods pilot for arandomised controlled trial

Background Urinary incontinence (UI) is a distressing condition affecting at least 5 million women in England and Wales. Traditionally, physiotherapy for UI comprises pelvic floor muscle training, but although evidence suggests this can be effective it is also recognised that benefits are often compromised by patient motivation and commitment. In addition, there is increasing recognition that physical symptoms alone are poor indicators of the impact of incontinence on individuals’ lives. Consequently, more holistic approaches to the treatment of UI, such as Modified Pilates (MP) have been recommended. This study aimed to provide preliminary findings about the effectiveness of a 6-week course of MP classes as an adjunct to standard physiotherapy care for UI, and to test the feasibility of a randomised controlled trial (RCT) design. Methods The study design was a single centre pilot RCT, plus qualitative interviews. 73 women referred to Women’s Health Physiotherapy Services for UI at Colchester Hospital University NHS Foundation Trust were randomly assigned to two groups: a 6-week course of MP classes in addition to standard physiotherapy care (intervention) or standard physiotherapy care only (control). Main outcome measures were self-reported UI, quality of life and self-esteem at baseline (T1), completion of treatment (T2), and 5 months after randomisation (T3). Qualitative interviews were conducted with a subgroup at T2 and T3. Due to the nature of the intervention blinding of participants, physiotherapists and researchers was not feasible. Results Post-intervention data revealed a range of benefits for women who attended MP classes and who had lower symptom severity at baseline: improved self-esteem (p = 0.032), decreased social embarrassment (p = 0.026) and lower impact on normal daily activities (p = 0.025). In contrast, women with higher symptom severity showed improvement in their personal relationships (p = 0.017). Qualitative analysis supported these findings and also indicated that MP classes could positively influence attitudes to exercise, diet and wellbeing. Conclusions A definitive RCT is feasible but will require a large sample size to inform clinical practice. Trial registration ISRCTN74075972 Registered 12/12/12 (Retrospectively registered)

Neutrophil mobilization via plerixafor-mediated CXCR4 inhibition arises from lung demargination and blockade of neutrophil homing to the bone marrow

Blood neutrophil homeostasis is essential for successful host defense against invading pathogens. Circulating neutrophil counts are positively regulated by CXCR2 signaling and negatively regulated by the CXCR4-CXCL12 axis. In particular, G-CSF, a known CXCR2 signaler, and plerixafor, a CXCR4 antagonist, have both been shown to correct neutropenia in human patients. G-CSF directly induces neutrophil mobilization from the bone marrow (BM) into the blood, but the mechanisms underlying plerixafor-induced neutrophilia remain poorly defined. Using a combination of intravital multiphoton microscopy, genetically modified mice and novel in vivo homing assays, we demonstrate that G-CSF and plerixafor work through distinct mechanisms. In contrast to G-CSF, CXCR4 inhibition via plerixafor does not result in neutrophil mobilization from the BM. Instead, plerixafor augments the frequency of circulating neutrophils through their release from the marginated pool present in the lung, while simultaneously preventing neutrophil return to the BM. Our study demonstrates for the first time that drastic changes in blood neutrophils can originate from alternative reservoirs other than the BM, while implicating a role for CXCR4-CXCL12 interactions in regulating lung neutrophil margination. Collectively, our data provides valuable insights into the fundamental regulation of neutrophil homeostasis, which may lead to the development of improved treatment regimens for neutropenic patients.This research was funded by SIgN, A*STAR, Singapore. C.N.Z. Mattar and J.K.Y. Chan received salary support from the National Medical Research Council of Singapore (NMRC/TA/003/2012 and NMRC/CSA/012/2009, respectively).S

Ca2+-Dependent Phosphorylation of RyR2 Can Uncouple Channel Gating from Direct Cytosolic Ca2+ Regulation

Phosphorylation of the cardiac ryanodine receptor (RyR2) is thought to be important not only for normal cardiac excitation-contraction coupling but also in exacerbating abnormalities in Ca2+ homeostasis in heart failure. Linking phosphorylation to specific changes in the single-channel function of RyR2 has proved very difficult, yielding much controversy within the field. We therefore investigated the mechanistic changes that take place at the single-channel level after phosphorylating RyR2 and, in particular, the idea that PKA-dependent phosphorylation increases RyR2 sensitivity to cytosolic Ca2+. We show that hyperphosphorylation by exogenous PKA increases open probability (Po) but, crucially, RyR2 becomes uncoupled from the influence of cytosolic Ca2+; lowering [Ca2+] to subactivating levels no longer closes the channels. Phosphatase (PP1) treatment reverses these gating changes, returning the channels to a Ca2+-sensitive mode of gating. We additionally found that cytosolic incubation with Mg2+/ATP in the absence of exogenously added kinase could phosphorylate RyR2 in approximately 50% of channels, thereby indicating that an endogenous kinase incorporates into the bilayer together with RyR2. Channels activated by the endogenous kinase exhibited identical changes in gating behavior to those activated by exogenous PKA, including uncoupling from the influence of cytosolic Ca2+. We show that the endogenous kinase is both Ca2+-dependent and sensitive to inhibitors of PKC. Moreover, the Ca2+-dependent, endogenous kinase–induced changes in RyR2 gating do not appear to be related to phosphorylation of serine-2809. Further work is required to investigate the identity and physiological role of this Ca2+-dependent endogenous kinase that can uncouple RyR2 gating from direct cytosolic Ca2+ regulation