Planning for the New Normal : Using Build One Portsmouth to Address Flood Resilience

Sea level rise, recurrent flooding, and increasingly severe storms are ever-present threats to coastal Virginia. As climate change becomes the “new normal”, creative solutions are needed to adapt to these stark realities. In response to these climate-related challenges, Governor Ralph Northam issued Executive Order 24, “Increasing Virginia’s Resilience to Sea Level Rise and Natural Hazards,” on November 2, 2018. The Executive Order designated the Secretary of Natural Resources as the Chief Resilience Officer of the Commonwealth, and set forth various actions intended to increase statewide resilience to natural hazards and extreme weather. Later that same month, Portsmouth released its 2018 comprehensive plan, Build One Portsmouth, which also takes resiliency issues into account and attempts to increase the City’s preparedness moving forward. Considering these recent developments, it is important for Portsmouth to establish the boundaries of its authority as the City plans for the future. This memorandum attempts to answer some of the City’s most pressing questions in its efforts to become more resilient. This abstract has been taken from the authors\u27 introduction

Empirical constraints on extrusion mechanisms from the upper margin of an exhumed high-grade orogenic core, Sutlej valley, NW India

The Early–Middle Miocene exhumation of the crystalline core of the Himalaya is a relatively well-understood process compared to the preceding phase of burial and prograde metamorphism in the Eocene–Oligocene. Highly deformed rocks of the Greater Himalayan Sequence (GHS) dominate the crystalline core, and feature a strong metamorphic and structural overprint related to the younger exhumation. The Tethyan Sedimentary Series was tectonically separated from the underlying GHS during the Miocene by the South Tibetan Detachment, and records a protracted and complex history of Cenozoic deformation. Unfortunately these typically low-grade or unmetamorphosed rocks generally yield little quantitative pressure–temperature�time information to accompany this deformation history. In parts of the western Himalaya, however, the basal unit of the Tethyan Sedimentary Series (the Haimanta Group) includes pelites metamorphosed to amphibolite facies. This presents a unique opportunity to explore the tectono-thermal evolution of crystalline rocks which record the early history of the orogen. Pressure–temperature�time–deformation (P–T�t–d) paths modelled for two Haimanta Group pelitic rocks reveal three distinct stages of metamorphism: (1) prograde Barrovian metamorphism to 610–620 °C at c. 7–8 kbars, with garnet growing over an early tectonic fabric (S1); (2) initial decompression during heating to 640–660 °C at c. 6–7 kbars, with development of a pervasive crenulation cleavage (S2) and staurolite and kyanite porphyroblast growth; (3) further exhumation during cooling, with minor retrograde metamorphism and modification of the pervasive S2 fabric. Monazite growth ages constrain the timing of initial garnet growth (> 34 Ma), the start of D2 and maximum burial (c. 30 Ma), and the termination of garnet growth (c. 28 Ma). Muscovite Ar/Ar ages indicate cooling through c. 300 °C at c. 13 Ma, from which we derive an initial exhumation rate of c. 1.3 mm year? 1 for the Haimanta Group. The underlying GHS was exhumed at a rate of 2.2 to 3 mm year? 1 during this time. The difference in exhumation rate between these two units is considered to reflect Early Miocene displacement on the intervening South Tibetan Detachment. Slower exhumation (c. 0.6 mm year? 1) of both units after c. 13 Ma followed the cessation of major displacement on this structure, after which time the Haimanta Group and the GHS were exhumed as one relatively coherent tectonic block

An aberrant NOTCH2-BCR signaling axis in B cells from patients with chronic GVHD

B-cell receptor (BCR)-activated B cells contribute to pathogenesis in chronic graft-versus-host disease (cGVHD), a condition manifested by both B-cell autoreactivity and immune deficiency. We hypothesized that constitutive BCR activation precluded functional B-cell maturation in cGVHD. To address this, we examined BCR-NOTCH2 synergy because NOTCH has been shown to increase BCR responsiveness in normal mouse B cells. We conducted ex vivo activation and signaling assays of 30 primary samples from hematopoietic stem cell transplantation patients with and without cGVHD. Consistent with a molecular link between pathways, we found that BCR-NOTCH activation significantly increased the proximal BCR adapter protein BLNK. BCR-NOTCH activation also enabled persistent NOTCH2 surface expression, suggesting a positive feedback loop. Specific NOTCH2 blockade eliminated NOTCH-BCR activation and significantly altered NOTCH downstream targets and B-cell maturation/effector molecules. Examination of the molecular underpinnings of this “NOTCH2-BCR axis” in cGVHD revealed imbalanced expression of the transcription factors IRF4 and IRF8, each critical to B-cell differentiation and fate. All-trans retinoic acid (ATRA) increased IRF4 expression, restored the IRF4-to-IRF8 ratio, abrogated BCR-NOTCH hyperactivation, and reduced NOTCH2 expression in cGVHD B cells without compromising viability. ATRA-treated cGVHD B cells had elevated TLR9 and PAX5, but not BLIMP1 (a gene-expression pattern associated with mature follicular B cells) and also attained increased cytosine guanine dinucleotide responsiveness. Together, we reveal a mechanistic link between NOTCH2 activation and robust BCR responses to otherwise suboptimal amounts of surrogate antigen. Our findings suggest that peripheral B cells in cGVHD patients can be pharmacologically directed from hyperactivation toward maturity

Impacto da pré-eclâmpsia grave na saúde materna e fetal

Introduction: Pre-eclampsia, a serious gestational complication, involves hypertension and organ dysfunction after the 20th week, with complex etiology. Classified as mild and severe, the latter presents intense symptoms such as severe hypertension, proteinuria and organic dysfunction. As for diagnosis, clinical criteria and exams such as blood pressure measurement, urine analysis and ultrasound are used. Severe pre-eclampsia increases risks such as placental abruption, fetal growth restriction and premature birth, requiring hospital treatment and, in critical cases, immediate delivery. Investments in research are crucial to optimize the prevention and management of this complex condition. Objective: Therefore, the present study aims to analyze the impacts of severe preeclampsia on maternal and fetal health. Methodology: The study employs a methodological approach to literature review to comprehensively and updatedly analyze preeclampsia, maternal health, fetal health, and complications. The search was conducted across various platforms using specific descriptors, resulting in 295 items. After eliminating duplicates, inclusion criteria were applied, yielding 32 relevant articles from 2019 to 2024, in English, Portuguese, and Spanish. This rigorous selection ensured the relevance of the information to achieve the research objectives.Results and Discussion: Severe pre-eclampsia has significant impacts on mothers and fetuses, both in the short and long term. In the short term, maternal health is compromised, with risks of eclampsia, kidney failure, HELLP syndrome and placental abruption, often leading to premature birth. In the long term, women face a greater risk of cardiovascular disease, type 2 diabetes and kidney damage, with possible emotional repercussions. For fetuses, there are immediate risks such as growth restriction and neonatal complications, while studies point to an increased risk of cardiovascular diseases, metabolic disorders and neurological problems in adult life. The uniqueness of each case demands regular medical monitoring and preventive measures.Introdução: A pré-eclâmpsia, complicação gestacional grave, envolve hipertensão e disfunção de órgãos após a 20ª semana, com etiologia complexa. Classificada em leve e grave, esta última apresenta sintomas intensos como hipertensão severa, proteinúria e disfunção orgânica. Quanto ao diagnóstico, utilizam-se critérios clínicos e exames como medição da pressão, análise de urina e ultrassonografia. A pré-eclâmpsia grave aumenta riscos como descolamento prematuro da placenta, restrição do crescimento fetal e parto prematuro, exigindo tratamento hospitalar e, em casos críticos, parto imediato. Investimentos em pesquisa são cruciais para otimizar a prevenção e manejo dessa condição complexa. Objetivo: Sendo, assim, o presente estudo tem como objetivo analisar os impactos da pré-eclâmpsia grave para saúde materna e fetal.  Metodologia: O estudo emprega uma abordagem metodológica de revisão de literatura para analisar de forma abrangente e atualizada a pré-eclâmpsia, saúde materna, saúde fetal e complicações. A busca foi realizada em diversas plataformas, utilizando descritores específicos, resultando em 295 itens. Após a eliminação de duplicatas, critérios de inclusão foram aplicados, resultando em 32 artigos relevantes de 2019 a 2024, em inglês, português e espanhol. Essa seleção rigorosa assegurou a pertinência das informações para alcançar os objetivos da pesquisa. Resultados e Discussão: A pré-eclâmpsia grave tem impactos significativos para mães e fetos, tanto a curto quanto a longo prazo. No curto prazo, a saúde materna é comprometida, com riscos de eclâmpsia, insuficiência renal, síndrome HELLP e descolamento prematuro da placenta, frequentemente levando a parto prematuro. A longo prazo, mulheres enfrentam maior risco de doenças cardiovasculares, diabetes tipo 2 e danos renais, com possíveis repercussões emocionais. Para os fetos, há riscos imediatos como restrição de crescimento e complicações neonatais, enquanto estudos apontam para aumento do risco de doenças cardiovasculares, distúrbios metabólicos e problemas neurológicos na vida adulta. A singularidade de cada caso demanda acompanhamento médico regular e medidas preventivas

Impact of opioid-free analgesia on pain severity and patient satisfaction after discharge from surgery: multispecialty, prospective cohort study in 25 countries

Background: Balancing opioid stewardship and the need for adequate analgesia following discharge after surgery is challenging. This study aimed to compare the outcomes for patients discharged with opioid versus opioid-free analgesia after common surgical procedures.Methods: This international, multicentre, prospective cohort study collected data from patients undergoing common acute and elective general surgical, urological, gynaecological, and orthopaedic procedures. The primary outcomes were patient-reported time in severe pain measured on a numerical analogue scale from 0 to 100% and patient-reported satisfaction with pain relief during the first week following discharge. Data were collected by in-hospital chart review and patient telephone interview 1 week after discharge.Results: The study recruited 4273 patients from 144 centres in 25 countries; 1311 patients (30.7%) were prescribed opioid analgesia at discharge. Patients reported being in severe pain for 10 (i.q.r. 1-30)% of the first week after discharge and rated satisfaction with analgesia as 90 (i.q.r. 80-100) of 100. After adjustment for confounders, opioid analgesia on discharge was independently associated with increased pain severity (risk ratio 1.52, 95% c.i. 1.31 to 1.76; P < 0.001) and re-presentation to healthcare providers owing to side-effects of medication (OR 2.38, 95% c.i. 1.36 to 4.17; P = 0.004), but not with satisfaction with analgesia (beta coefficient 0.92, 95% c.i. -1.52 to 3.36; P = 0.468) compared with opioid-free analgesia. Although opioid prescribing varied greatly between high-income and low- and middle-income countries, patient-reported outcomes did not.Conclusion: Opioid analgesia prescription on surgical discharge is associated with a higher risk of re-presentation owing to side-effects of medication and increased patient-reported pain, but not with changes in patient-reported satisfaction. Opioid-free discharge analgesia should be adopted routinely

Global burden of 369 diseases and injuries in 204 countries and territories, 1990–2019: a systematic analysis for the Global Burden of Disease Study 2019

Background: In an era of shifting global agendas and expanded emphasis on non-communicable diseases and injuries along with communicable diseases, sound evidence on trends by cause at the national level is essential. The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) provides a systematic scientific assessment of published, publicly available, and contributed data on incidence, prevalence, and mortality for a mutually exclusive and collectively exhaustive list of diseases and injuries. Methods: GBD estimates incidence, prevalence, mortality, years of life lost (YLLs), years lived with disability (YLDs), and disability-adjusted life-years (DALYs) due to 369 diseases and injuries, for two sexes, and for 204 countries and territories. Input data were extracted from censuses, household surveys, civil registration and vital statistics, disease registries, health service use, air pollution monitors, satellite imaging, disease notifications, and other sources. Cause-specific death rates and cause fractions were calculated using the Cause of Death Ensemble model and spatiotemporal Gaussian process regression. Cause-specific deaths were adjusted to match the total all-cause deaths calculated as part of the GBD population, fertility, and mortality estimates. Deaths were multiplied by standard life expectancy at each age to calculate YLLs. A Bayesian meta-regression modelling tool, DisMod-MR 2.1, was used to ensure consistency between incidence, prevalence, remission, excess mortality, and cause-specific mortality for most causes. Prevalence estimates were multiplied by disability weights for mutually exclusive sequelae of diseases and injuries to calculate YLDs. We considered results in the context of the Socio-demographic Index (SDI), a composite indicator of income per capita, years of schooling, and fertility rate in females younger than 25 years. Uncertainty intervals (UIs) were generated for every metric using the 25th and 975th ordered 1000 draw values of the posterior distribution. Findings: Global health has steadily improved over the past 30 years as measured by age-standardised DALY rates. After taking into account population growth and ageing, the absolute number of DALYs has remained stable. Since 2010, the pace of decline in global age-standardised DALY rates has accelerated in age groups younger than 50 years compared with the 1990–2010 time period, with the greatest annualised rate of decline occurring in the 0–9-year age group. Six infectious diseases were among the top ten causes of DALYs in children younger than 10 years in 2019: lower respiratory infections (ranked second), diarrhoeal diseases (third), malaria (fifth), meningitis (sixth), whooping cough (ninth), and sexually transmitted infections (which, in this age group, is fully accounted for by congenital syphilis; ranked tenth). In adolescents aged 10–24 years, three injury causes were among the top causes of DALYs: road injuries (ranked first), self-harm (third), and interpersonal violence (fifth). Five of the causes that were in the top ten for ages 10–24 years were also in the top ten in the 25–49-year age group: road injuries (ranked first), HIV/AIDS (second), low back pain (fourth), headache disorders (fifth), and depressive disorders (sixth). In 2019, ischaemic heart disease and stroke were the top-ranked causes of DALYs in both the 50–74-year and 75-years-and-older age groups. Since 1990, there has been a marked shift towards a greater proportion of burden due to YLDs from non-communicable diseases and injuries. In 2019, there were 11 countries where non-communicable disease and injury YLDs constituted more than half of all disease burden. Decreases in age-standardised DALY rates have accelerated over the past decade in countries at the lower end of the SDI range, while improvements have started to stagnate or even reverse in countries with higher SDI. Interpretation: As disability becomes an increasingly large component of disease burden and a larger component of health expenditure, greater research and developm nt investment is needed to identify new, more effective intervention strategies. With a rapidly ageing global population, the demands on health services to deal with disabling outcomes, which increase with age, will require policy makers to anticipate these changes. The mix of universal and more geographically specific influences on health reinforces the need for regular reporting on population health in detail and by underlying cause to help decision makers to identify success stories of disease control to emulate, as well as opportunities to improve. Funding: Bill & Melinda Gates Foundation. © 2020 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 licens

Azimuthal anisotropy of charged jet production in root s(NN)=2.76 TeV Pb-Pb collisions

We present measurements of the azimuthal dependence of charged jet production in central and semi-central root s(NN) = 2.76 TeV Pb-Pb collisions with respect to the second harmonic event plane, quantified as nu(ch)(2) (jet). Jet finding is performed employing the anti-k(T) algorithm with a resolution parameter R = 0.2 using charged tracks from the ALICE tracking system. The contribution of the azimuthal anisotropy of the underlying event is taken into account event-by-event. The remaining (statistical) region-to-region fluctuations are removed on an ensemble basis by unfolding the jet spectra for different event plane orientations independently. Significant non-zero nu(ch)(2) (jet) is observed in semi-central collisions (30-50% centrality) for 20 <p(T)(ch) (jet) <90 GeV/c. The azimuthal dependence of the charged jet production is similar to the dependence observed for jets comprising both charged and neutral fragments, and compatible with measurements of the nu(2) of single charged particles at high p(T). Good agreement between the data and predictions from JEWEL, an event generator simulating parton shower evolution in the presence of a dense QCD medium, is found in semi-central collisions. (C) 2015 CERN for the benefit of the ALICE Collaboration. Published by Elsevier B.V. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).Peer reviewe

Production of He-4 and (4) in Pb-Pb collisions at root(NN)-N-S=2.76 TeV at the LHC

Results on the production of He-4 and (4) nuclei in Pb-Pb collisions at root(NN)-N-S = 2.76 TeV in the rapidity range vertical bar y vertical bar <1, using the ALICE detector, are presented in this paper. The rapidity densities corresponding to 0-10% central events are found to be dN/dy4(He) = (0.8 +/- 0.4 (stat) +/- 0.3 (syst)) x 10(-6) and dN/dy4 = (1.1 +/- 0.4 (stat) +/- 0.2 (syst)) x 10(-6), respectively. This is in agreement with the statistical thermal model expectation assuming the same chemical freeze-out temperature (T-chem = 156 MeV) as for light hadrons. The measured ratio of (4)/He-4 is 1.4 +/- 0.8 (stat) +/- 0.5 (syst). (C) 2018 Published by Elsevier B.V.Peer reviewe