Physically-based Assessment of Hurricane Surge Threat under Climate Change

Storm surges are responsible for much of the damage and loss of life associated with landfalling hurricanes. Understanding how global warming will affect hurricane surges thus holds great interest. As general circulation models (GCMs) cannot simulate hurricane surges directly, we couple a GCM-driven hurricane model with hydrodynamic models to simulate large numbers of synthetic surge events under projected climates and assess surge threat, as an example, for New York City (NYC). Struck by many intense hurricanes in recorded history and prehistory, NYC is highly vulnerable to storm surges. We show that the change of storm climatology will probably increase the surge risk for NYC; results based on two GCMs show the distribution of surge levels shifting to higher values by a magnitude comparable to the projected sea-level rise (SLR). The combined effects of storm climatology change and a 1 m SLR may cause the present NYC 100-yr surge flooding to occur every 3–20 yr and the present 500-yr flooding to occur every 25–240 yr by the end of the century.United States. National Oceanic and Atmospheric Administration (Postdoctoral Fellowship Program)National Science Foundation (U.S.

The future of midlatitude cyclones

This is the final version. Available from the publisher via the DOI in this record.Purpose of Review This review brings together recent research on the structure, characteristics, dynamics, and impacts of extratropical cyclones in the future. It draws on research using idealized models and complex climate simulations, to evaluate what is known and unknown about these future changes. Recent Findings There are interacting processes that contribute to the uncertainties in future extratropical cyclone changes, e.g., changes in the horizontal and vertical structure of the atmosphere and increasing moisture content due to rising temperatures. Summary While precipitation intensity will most likely increase, along with associated increased latent heating, it is unclear to what extent and for which particular climate conditions this will feedback to increase the intensity of the cyclones. Future research could focus on bridging the gap between idealized models and complex climate models, as well as better understanding of the regional impacts of future changes in extratropical cyclones.Natural Environment Research Council (NERC

Effect of mass drug administration on malaria incidence in southeast Senegal during 2020–22: a two-arm, open-label, cluster-randomised controlled trial

BackgroundIn Africa, the scale-up of malaria-control interventions has reduced malaria burden, but progress towards elimination has stalled. Mass drug administration (MDA) is promising as a transmission-reducing strategy, but evidence from low-to-moderate transmission settings is needed. We aimed to assess the safety, coverage, and effect of three cycles of MDA with dihydroartemisinin-piperaquine plus single, low-dose primaquine on Plasmodium falciparum incidence and prevalence in southeast Senegal.MethodsWe conducted a two-arm, open-label, cluster-randomised controlled trial in villages in the Tambacounda health district of southeast Senegal. Eligible villages had a population size of 200-800, were within a health-post catchment area with an annual malaria incidence of 60-160 cases per 1000 people, and had an established or planned Prise en Charge à Domicile Plus model. We randomly assigned villages (1:1) using a stratified, constrained randomisation approach to receive either three cycles of MDA with oral dihydroartemisinin-piperaquine plus single, low-dose primaquine administered at 6-week intervals (intervention) or to standard of care, which included three cycles of seasonal malaria chemoprevention (SMC) with oral sulfadoxine-pyrimethamine plus amodiaquine administered at 4-week intervals (control). Participants, the field team, and all investigators, including those who assessed outcomes and analysed data, were unmasked to allocation assignment. Laboratory technicians were masked to intervention assignment. The primary outcome was village-level, P falciparum-confirmed malaria incidence in the post-intervention year (ie, July to December, 2022). Secondary outcomes included malaria incidence during the intervention year (ie, July to December, 2021), coverage and safety of MDA, and adverse events. We conducted analyses using an intention-to-treat approach. The trial is registered with ClinicalTrials.gov (NCT04864444) and is completed.FindingsBetween Sept 1 and Oct 25, 2020, 523 villages were geolocated and screened for eligibility; 111 met the inclusion criteria. Of these, 60 villages were randomly selected and assigned to the intervention arm or control arm. Distribution coverage of all three doses of dihydroartemisinin-piperaquine was 6057 (73·6%) of 8229 participants in the first cycle, 6836 (78·8%) of 8673 participants in the second cycle, and 7065 (81·3%) of 8690 participants in the third cycle. Distribution coverage of single, low-dose primaquine was 6286 (78·6%) of 7999 participants in the first cycle, 6949 (82·1%) of 8462 participants in the second cycle, and 7199 (84·0%) of 8575 participants in the third cycle. Distribution coverage of all three doses of SMC was 3187 (92·2%) of 3457 children aged 3-120 months in the first cycle, 3158 (91·8%) of 3442 children aged 3-120 months in the second cycle, and 3139 (91·4%) of 3434 children aged 3-120 months in the third cycle. In the intervention year (ie, July to December, 2021), the adjusted effect of MDA was 55% (95% CI 28 to 71). In the post-intervention year (ie, July to December 2022), the adjusted MDA effect was 26% (-17 to 53). Malaria incidence during the transmission season of the post-intervention year was 126 cases per 1000 population in the intervention arm and 146 cases per 1000 population in the control arm. No serious adverse events were reported.InterpretationIn southeast Senegal, a low-to-moderate transmission setting where malaria-control measures have been scaled up, three cycles of MDA with dihydroartemisinin-piperaquine plus single, low-dose primaquine was safe and reduced malaria burden during the intervention year. However, its sustained effect was weak and continuation of MDA or another transmission-reducing strategy could be required.FundingUS President's Malaria Initiative

Catch-Up Growth Following Fetal Growth Restriction Promotes Rapid Restoration of Fat Mass but Without Metabolic Consequences at One Year of Age

BACKGROUND: Fetal growth restriction (FGR) followed by rapid weight gain during early life has been suggested to be the initial sequence promoting central adiposity and insulin resistance. However, the link between fetal and early postnatal growth and the associated anthropometric and metabolic changes have been poorly studied. METHODOLOGY/PRINCIPAL FINDINGS: Over the first year of post-natal life, changes in body mass index, skinfold thickness and hormonal concentrations were prospectively monitored in 94 infants in whom the fetal growth velocity had previously been measured using a repeated standardized procedure of ultrasound fetal measurements. 45 infants, thinner at birth, had experienced previous FGR (FGR+) regardless of birth weight. Growth pattern in the first four months of life was characterized by greater change in BMI z-score in FGR+ (+1.26+/-1.2 vs +0.58 +/-1.17 SD in FGR-) resulting in the restoration of BMI and of fat mass to values similar to FGR-, independently of caloric intakes. Growth velocity after 4 months was similar and BMI z-score and fat mass remained similar at 12 months of age. At both time-points, fetal growth velocity was an independent predictor of fat mass in FGR+. At one year, fasting insulin levels were not different but leptin was significantly higher in the FGR+ (4.43+/-1.41 vs 2.63+/-1 ng/ml in FGR-). CONCLUSION: Early catch-up growth is related to the fetal growth pattern itself, irrespective of birth weight, and is associated with higher insulin sensitivity and lower leptin levels after birth. Catch-up growth promotes the restoration of body size and fat stores without detrimental consequences at one year of age on body composition or metabolic profile. The higher leptin concentration at one year may reflect a positive energy balance in children who previously faced fetal growth restriction

Brain injury-associated biomarkers of TGF-beta1, S100B, GFAP, NF-L, tTG, AbetaPP, and tau were concomitantly enhanced and the UPS was impaired during acute brain injury caused by Toxocara canis in mice

BACKGROUND: Because the outcomes and sequelae after different types of brain injury (BI) are variable and difficult to predict, investigations on whether enhanced expressions of BI-associated biomarkers (BIABs), including transforming growth factor beta1 (TGF-beta1), S100B, glial fibrillary acidic protein (GFAP), neurofilament light chain( NF-L), tissue transglutaminases (tTGs), beta-amyloid precursor proteins (AbetaPP), and tau are present as well as whether impairment of the ubiquitin-proteasome system (UPS) is present have been widely used to help delineate pathophysiological mechanisms in various BIs. Larvae of Toxocara canis can invade the brain and cause BI in humans and mice, leading to cerebral toxocariasis (CT). Because the parasitic burden is light in CT, it may be too cryptic to be detected in humans, making it difficult to clearly understand the pathogenesis of subtle BI in CT. Since the pathogenesis of murine toxocariasis is very similar to that in humans, it appears appropriate to use a murine model to investigate the pathogenesis of CT. METHODS: BIAB expressions and UPS function in the brains of mice inoculated with a single dose of 250 T. canis embryonated eggs was investigated from 3 days (dpi) to 8 weeks post- infection (wpi) by Western blotting and RT-PCR. RESULTS: Results revealed that at 4 and 8 wpi, T. canis larvae were found to have invaded areas around the choroid plexus but without eliciting leukocyte infiltration in brains of infected mice; nevertheless, astrogliosis, an indicator of BI, with 78.9~142.0-fold increases in GFAP expression was present. Meanwhile, markedly increased levels of other BIAB proteins including TGF-beta1, S100B, NF-L, tTG, AbetaPP, and tau, with increases ranging 2.0~12.0-fold were found, although their corresponding mRNA expressions were not found to be present at 8 wpi. Concomitantly, UPS impairment was evidenced by the overexpression of conjugated ubiquitin and ubiquitin in the brain. CONCLUSION: Further studies are needed to determine whether there is an increased risk of CT progression into neurodegenerative disease because neurodegeneration-associated AbetaPP and phosphorylated tau emerged in the brain. DOI: 10.1186/1471-2334-8-8

Alzheimer disease models and human neuropathology: similarities and differences

Animal models aim to replicate the symptoms, the lesions or the cause(s) of Alzheimer disease. Numerous mouse transgenic lines have now succeeded in partially reproducing its lesions: the extracellular deposits of Aβ peptide and the intracellular accumulation of tau protein. Mutated human APP transgenes result in the deposition of Aβ peptide, similar but not identical to the Aβ peptide of human senile plaque. Amyloid angiopathy is common. Besides the deposition of Aβ, axon dystrophy and alteration of dendrites have been observed. All of the mutations cause an increase in Aβ 42 levels, except for the Arctic mutation, which alters the Aβ sequence itself. Overexpressing wild-type APP alone (as in the murine models of human trisomy 21) causes no Aβ deposition in most mouse lines. Doubly (APP × mutated PS1) transgenic mice develop the lesions earlier. Transgenic mice in which BACE1 has been knocked out or overexpressed have been produced, as well as lines with altered expression of neprilysin, the main degrading enzyme of Aβ. The APP transgenic mice have raised new questions concerning the mechanisms of neuronal loss, the accumulation of Aβ in the cell body of the neurons, inflammation and gliosis, and the dendritic alterations. They have allowed some insight to be gained into the kinetics of the changes. The connection between the symptoms, the lesions and the increase in Aβ oligomers has been found to be difficult to unravel. Neurofibrillary tangles are only found in mouse lines that overexpress mutated tau or human tau on a murine tau −/− background. A triply transgenic model (mutated APP, PS1 and tau) recapitulates the alterations seen in AD but its physiological relevance may be discussed. A number of modulators of Aβ or of tau accumulation have been tested. A transgenic model may be analyzed at three levels at least (symptoms, lesions, cause of the disease), and a reading key is proposed to summarize this analysis

Laddered motivations of external whistleblowers: The truth about attributes, consequences, and values

The purpose of this study was to explore the motivational structures of external whistleblowers involved in the decision to blow the whistle by applying MEC theory and the laddering technique. Using both soft and hard laddering methods, data were collected from 37 Korean external whistleblowers. Results revealed that the means-end chain of external whistleblow-ers was the hierarchical linkage among two concrete attributes (the power of external whistleblowing to make changes and its warning about the seriousness of wrongdoing to the public), two functional consequences (correcting a wrongdoing and making those who violated laws admit their offenses), and one terminal value (the truth). The extant whistleblowing literature has either made assumptions about whistleblowers’ motivations when developing models or has drawn indirect inferences from measures of other variables. Our study is the first with an explicit and empirical focus on whistleblowers’ motivations. The findings provide evidence of the motivational structures of external whistleblowers that consist of a set of complex paths linked by multi-layered motivators. This research will be helpful in designing and reviewing whistleblowing programs for organizations, regulatory agencies, and journalists

Anthropogenic intensification of short-duration rainfall extremes

Short- duration (1-3 h) rainfall extremes can cause serious damage to societies through rapidly developing (flash) flooding and are determined by complex, multifaceted processes that are altering as Earth's climate warms. In this Review, we examine evidence from observational, theoretical and modelling studies for the intensification of these rainfall extremes, the drivers and the impact on flash flooding. Both short- duration and long- duration (\textgreater1 day) rainfall extremes are intensifying with warming at a rate consistent with the increase in atmospheric moisture (~7% K-1), while in some regions, increases in short- duration extreme rainfall intensities are stronger than expected from moisture increases alone. These stronger local increases are related to feedbacks in convective clouds, but their exact role is uncertain because of the very small scales involved. Future extreme rainfall intensification is also modulated by changes to temperature stratification and large- scale atmospheric circulation. The latter remains a major source of uncertainty. Intensification of short- duration extremes has likely increased the incidence of flash flooding at local scales and this can further compound with an increase in storm spatial footprint to considerably increase total event rainfall. These findings call for urgent climate change adaptation measures to manage increasing flood risks