Relations and Equivalences Between Circuit Lower Bounds and Karp-Lipton Theorems

A frontier open problem in circuit complexity is to prove P^{NP} is not in SIZE[n^k] for all k; this is a necessary intermediate step towards NP is not in P_{/poly}. Previously, for several classes containing P^{NP}, including NP^{NP}, ZPP^{NP}, and S_2 P, such lower bounds have been proved via Karp-Lipton-style Theorems: to prove C is not in SIZE[n^k] for all k, we show that C subset P_{/poly} implies a "collapse" D = C for some larger class D, where we already know D is not in SIZE[n^k] for all k. It seems obvious that one could take a different approach to prove circuit lower bounds for P^{NP} that does not require proving any Karp-Lipton-style theorems along the way. We show this intuition is wrong: (weak) Karp-Lipton-style theorems for P^{NP} are equivalent to fixed-polynomial size circuit lower bounds for P^{NP}. That is, P^{NP} is not in SIZE[n^k] for all k if and only if (NP subset P_{/poly} implies PH subset i.o.- P^{NP}_{/n}). Next, we present new consequences of the assumption NP subset P_{/poly}, towards proving similar results for NP circuit lower bounds. We show that under the assumption, fixed-polynomial circuit lower bounds for NP, nondeterministic polynomial-time derandomizations, and various fixed-polynomial time simulations of NP are all equivalent. Applying this equivalence, we show that circuit lower bounds for NP imply better Karp-Lipton collapses. That is, if NP is not in SIZE[n^k] for all k, then for all C in {Parity-P, PP, PSPACE, EXP}, C subset P_{/poly} implies C subset i.o.-NP_{/n^epsilon} for all epsilon > 0. Note that unconditionally, the collapses are only to MA and not NP. We also explore consequences of circuit lower bounds for a sparse language in NP. Among other results, we show if a polynomially-sparse NP language does not have n^{1+epsilon}-size circuits, then MA subset i.o.-NP_{/O(log n)}, MA subset i.o.-P^{NP[O(log n)]}, and NEXP is not in SIZE[2^{o(m)}]. Finally, we observe connections between these results and the "hardness magnification" phenomena described in recent works

Effect of Exercise on Cardiometabolic Risk Factors in Adults With Chronic Spinal Cord Injury:A Systematic Review

Objective: To determine the effects of exercise on individual cardiometabolic syndrome (CMS) risk factors in adults with chronic spinal cord injury (SCI). Data Sources: English language searches of PubMed, Web of Science, EMBASE, and Scopus (January 1, 1970, to July 31, 2019). Study Selection: Articles were included if they met the following criteria: (1) original articles with statistical analysis, (2) participants were adults with a SCI sustained ≥1 year ago, (3) exercise intervention duration ≥2 weeks, and (4) included any CMS risk factor as an outcome. Data Extraction: The methodological quality of articles was assessed using the Downs and Black score. Data Synthesis: Sixty-five studies were included for the final analysis, including 9 studies classified as high quality (≥66.7%), 35 studies classified as fair quality (50%-66.6%), and 21 studies classified as low quality (&lt;50%). Improvements in waist circumference (4/6 studies) and markers of hepatic insulin sensitivity (4/5 studies) were reported following upper body aerobic exercise training, but no improvements in fasting glucose (8/8 studies), lipid profile (6/8 studies), systolic blood pressure (8/9 studies), or diastolic blood pressure (9/9 studies) were observed. Improvements in markers of peripheral insulin sensitivity (5/6 studies) were observed following functional electrical stimulation (FES) cycling. Improvements in lipid profile (4/5 studies) were observed following upper body resistance training (RT) (with or without aerobic exercise). No consistent improvements in CMS risk factors were observed following assisted ambulation, FES hybrid, FES rowing, and FES RT. Conclusions: Upper body aerobic exercise training (&gt;75% maximum heart rate) appears to improve waist circumference and hepatic insulin sensitivity but appears insufficient for improving fasting glucose, lipid profile, or resting blood pressure. The addition of RT to upper body aerobic exercise may elicit favorable changes in the lipid profile. More high-quality studies are needed to confirm if FES cycling is effective at improving peripheral insulin sensitivity.</p

Evidence that breast cancer risk at the 2q35 locus is mediated through IGFBP5 regulation.

GWAS have identified a breast cancer susceptibility locus on 2q35. Here we report the fine mapping of this locus using data from 101,943 subjects from 50 case-control studies. We genotype 276 SNPs using the 'iCOGS' genotyping array and impute genotypes for a further 1,284 using 1000 Genomes Project data. All but two, strongly correlated SNPs (rs4442975 G/T and rs6721996 G/A) are excluded as candidate causal variants at odds against >100:1. The best functional candidate, rs4442975, is associated with oestrogen receptor positive (ER+) disease with an odds ratio (OR) in Europeans of 0.85 (95% confidence interval=0.84-0.87; P=1.7 × 10(-43)) per t-allele. This SNP flanks a transcriptional enhancer that physically interacts with the promoter of IGFBP5 (encoding insulin-like growth factor-binding protein 5) and displays allele-specific gene expression, FOXA1 binding and chromatin looping. Evidence suggests that the g-allele confers increased breast cancer susceptibility through relative downregulation of IGFBP5, a gene with known roles in breast cell biology

Sustainability determinants of an intervention to identify clinical deterioration and improve childhood cancer survival in Latin American hospitals: The INSPIRE study protocol

BACKGROUND: More than 90% of children with cancer live in low-resourced settings, where survival is only 20%. Sustainable evidence-based (EB) interventions yielding ongoing beneficial patient outcomes are critical to improve childhood cancer survival. A better understanding of factors promoting intervention sustainability in these settings is urgently needed. The aim of this study is to provide an empirical understanding of how clinical capacity for sustainability, or the resources needed to sustain an intervention, impacts the sustainment of Pediatric Early Warning System (PEWS), an EB intervention that improves pediatric oncology outcomes in low-resource hospitals by detecting clinical deterioration and preventing the need for more intense treatment. METHODS: We will conduct a prospective, longitudinal study of approximately 100 resource-variable hospitals implementing and sustaining PEWS participating in Proyecto EVAT, a quality improvement collaborative of Latin American pediatric oncology centers. Aim 1: We will evaluate how clinical capacity for sustainability changes over time through 5 to 9 prospective measurements of capacity via survey of clinical staff using PEWS (approximately n = 13 per center) during the phases of PEWS adoption, implementation, and sustainability using the Clinical Sustainability Assessment Tool (CSAT). Aim 2: We will determine the relationship between capacity and a) PEWS sustainment and b) clinical deterioration mortality among pediatric oncology patients at centers sustaining PEWS for 2 to 10 years using chart review and an existing patient outcomes registry. Aim 3: We will develop novel strategies to promote sustainability by gaining a deeper understanding of perceived challenges to building capacity and PEWS sustainment. In combination with quantitative outcomes, we will conduct 24 focus groups with staff (doctors, nurses, and administrators) from hospitals with both high (n = 4) and low capacity (n = 4). We will then use implementation mapping to generate theoretically driven, empirically-supported sustainability strategies. DISCUSSION: This study will advance implementation science by providing a theoretically driven, foundational understanding of factors that predict sustainability among a large, diverse cohort of hospitals. We will then use this knowledge to develop sustainability evidence-informed strategies that optimize capacity and promote long-term sustainment of PEWS and improvements in patient outcomes, thus promoting equity in childhood cancer care globally

Sustainable management of groundwater extraction: An Australian perspective on current challenges

Study focus: Our incomplete knowledge of groundwater systems and processes imposes barriers in attempting to manage groundwater sustainably. Challenges also arise through complex institutional arrangements and decision-making processes, and the difficulty in involving stakeholders. In some areas, these difficulties have led to water table decline and impacts on groundwater users and groundwater-dependent ecosystems. However, there is potential to improve the sustainable use of groundwater resources through improvements in management practices. We discuss some of the challenges, and present survey results of research, government, and industry professionals across the groundwater sector in Australia. New hydrological insights for the region: The highest-ranked challenge identified in the survey was the difficulty in determining regional-scale volumetric water extraction limits. This is surprising given the criticism in the international literature of volumetric based approaches for groundwater management, and the decreased reliance on this approach in Australia and elsewhere in recent years. Other major challenges are the difficulty in determining and implementing maximum drawdown criteria for groundwater levels, determining water needs of ecosystems, and managing groundwater impacts on surface water. Notwithstanding these gaps in technical understanding and tools and a lack of resources for groundwater studies, improvements in stakeholder communication should enable more effective decision-making and improve compliance with regulations designed to protect groundwater and dependent ecosystems

Myths and Methodologies:Standardisation in human physiology research—should we control the controllables?

The premise of research in human physiology is to explore a multifaceted system whilst identifying one or a few outcomes of interest. Therefore, the control of potentially confounding variables requires careful thought regarding the extent of control and complexity of standardisation. One common factor to control prior to testing is diet, as food and fluid provision may deviate from participants’ habitual diets, yet a self‐report and replication method can be flawed by under‐reporting. Researchers may also need to consider standardisation of physical activity, whether it be through familiarisation trials, wash‐out periods, or guidance on levels of physical activity to be achieved before trials. In terms of pharmacological agents, the ethical implications of standardisation require researchers to carefully consider how medications, caffeine consumption and oral contraceptive prescriptions may affect the study. For research in females, it should be considered whether standardisation between‐ or within‐participants in regards to menstrual cycle phase is most relevant. The timing of measurements relative to various other daily events is relevant to all physiological research and so it can be important to standardise when measurements are made. This review summarises the areas of standardisation which we hope will be considered useful to anyone involved in human physiology research, including when and how one can apply standardisation to various contexts

Mental Health and Clinical Psychological Science in the Time of COVID-19: Challenges, Opportunities, and a Call to Action

COVID-19 presents significant social, economic, and medical challenges. Because COVID-19 has already begun to precipitate huge increases in mental health problems, clinical psychological science must assert a leadership role in guiding a national response to this secondary crisis. In this article, COVID-19 is conceptualized as a unique, compounding, multidimensional stressor that will create a vast need for intervention and necessitate new paradigms for mental health service delivery and training. Urgent challenge areas across developmental periods are discussed, followed by a review of psychological symptoms that likely will increase in prevalence and require innovative solutions in both science and practice. Implications for new research directions, clinical approaches, and policy issues are discussed to highlight the opportunities for clinical psychological science to emerge as an updated, contemporary field capable of addressing the burden of mental illness and distress in the wake of COVID-19 and beyond

Characteristics and Evolution of sill-driven off-axis hydrothermalism in Guaymas Basin – the Ringvent site

The Guaymas Basin spreading center, at 2000 m depth in the Gulf of California, is overlain by a thick sedimentary cover. Across the basin, localized temperature anomalies, with active methane venting and seep fauna exist in response to magma emplacement into sediments. These sites evolve over thousands of years as magma freezes into doleritic sills and the system cools. Although several cool sites resembling cold seeps have been characterized, the hydrothermally active stage of an off-axis site was lacking good examples. Here, we present a multidisciplinary characterization of Ringvent, an ~1 km wide circular mound where hydrothermal activity persists ~28 km northwest of the spreading center. Ringvent provides a new type of intermediate-stage hydrothermal system where off-axis hydrothermal activity has attenuated since its formation, but remains evident in thermal anomalies, hydrothermal biota coexisting with seep fauna, and porewater biogeochemical signatures indicative of hydrothermal circulation. Due to their broad potential distribution, small size and limited life span, such sites are hard to find and characterize, but they provide critical missing links to understand the complex evolution of hydrothermal systems