Incidence and costs of injuries to children and adults in the United States

Background: Injuries are a leading cause of death and acquired disability, and result in significant medical spending. Prior estimates of injury-related cost have been limited by older data, for certain population, or specific mechanisms. Findings: This study estimated the incidence of hospital-treated nonfatal injuries in the United States (US) in 2013 and the related comprehensive costs. Injury-related emergency department (ED) visits and hospitalizations were identified using 2013 Healthcare Cost and Utilization Project (HCUP) data. Models estimated the costs of medical spending and lost future work due to injuries in 2013 U.S. dollars. A total of 31,038,072 nonfatal injury-related hospitalizations and ED visits were identified, representing 9.8 per 100 people. Hospital-treated nonfatal injuries cost an estimated $1.853 trillion, including$168 billion in medical spending, $223 billion in work losses, and$1.461 trillion in quality of life losses. Conclusions: Approximately one in 10 individuals in the US is treated in the hospital for injury each year, with high corresponding costs. These data support priority-setting to reduce the injury burden in the US

Interventions for chronic kidney disease in people with sickle cell disease.

Background: Sickle cell disease (SCD), one of the commonest severe monogenic disorders, is caused by the inheritance of two abnormal haemoglobin (beta‐globin) genes. SCD can cause severe pain, significant end‐organ damage, pulmonary complications, and premature death. Kidney disease is a frequent and potentially severe complication in people with SCD. Chronic kidney disease (CKD) is defined as abnormalities of kidney structure or function present for more than three months. Sickle cell nephropathy refers to the spectrum of kidney complications in SCD. Glomerular damage is a cause of microalbuminuria and can develop at an early age in children with SCD, with increased prevalence in adulthood. In people with sickle cell nephropathy, outcomes are poor as a result of the progression to proteinuria and chronic kidney insufficiency. Up to 12% of people who develop sickle cell nephropathy will develop end‐stage renal disease. This is an update of a review first published in 2017. Objectives: To assess the effectiveness of any intervention for preventing or reducing kidney complications or chronic kidney disease in people with sickle cell disease. Possible interventions include red blood cell transfusions, hydroxyurea, and angiotensin‐converting enzyme inhibitors (ACEIs), either alone or in combination. Search methods: We searched for relevant trials in the Cochrane Cystic Fibrosis and Genetic Disorders Group Trials Register, CENTRAL, MEDLINE, Embase, seven other databases, and two other trials registers. Selection criteria: Randomised controlled trials (RCTs) comparing interventions to prevent or reduce kidney complications or CKD in people with SCD. We applied no restrictions related to outcomes examined, language, or publication status. Data collection and analysis: Two review authors independently assessed trial eligibility, extracted data, assessed the risk of bias, and assessed the certainty of the evidence (GRADE). Main results: We included three RCTs with 385 participants. We rated the certainty of the evidence as low to very low across different outcomes according to GRADE methodology, downgrading for risk of bias concerns, indirectness, and imprecision. Hydroxyurea versus placebo One RCT published in 2011 compared hydroxyurea to placebo in 193 children aged nine to 18 months. We are unsure if hydroxyurea compared to placebo reduces or prevents progression of kidney disease assessed by change in glomerular filtration rate (mean difference (MD) 0.58 mL/min /1.73 m2, 95% confidence interval (CI) −14.60 to 15.76; 142 participants; very low certainty). Hydroxyurea compared to placebo may improve the ability to concentrate urine (MD 42.23 mOsm/kg, 95% CI 12.14 to 72.32; 178 participants; low certainty), and may make little or no difference to SCD‐related serious adverse events, including acute chest syndrome (risk ratio (RR) 0.39, 99% CI 0.13 to 1.16; 193 participants; low certainty), painful crisis (RR 0.68, 99% CI 0.45 to 1.02; 193 participants; low certainty); and hospitalisations (RR 0.83, 99% CI 0.68 to 1.01; 193 participants; low certainty). No deaths occurred in either trial arm and the RCT did not report quality of life. Angiotensin‐converting enzyme inhibitors versus placebo One RCT published in 1998 compared an ACEI (captopril) to placebo in 22 adults with normal blood pressure and microalbuminuria. We are unsure if captopril compared to placebo reduces proteinuria (MD −49.00 mg/day, 95% CI −124.10 to 26.10; 22 participants; very low certainty). We are unsure if captopril reduces or prevents kidney disease as measured by creatinine clearance; the trial authors stated that creatinine clearance remained constant over six months in both groups, but provided no comparative data (very low certainty). The RCT did not report serious adverse events, all‐cause mortality, or quality of life. Angiotensin‐converting enzyme inhibitors versus vitamin C One RCT published in 2020 compared an ACEI (lisinopril) with vitamin C in 170 children aged one to 18 years with normal blood pressure and microalbuminuria. It reported no data we could analyse. We are unsure if lisinopril compared to vitamin C reduces proteinuria in this population: the large drop in microalbuminuria in both arms of the trial after only one month on treatment may have been due to an overestimation of microalbuminuria at baseline rather than a true effect. The RCT did not report serious adverse events, all‐cause mortality, or quality of life. Authors' conclusions We are unsure if hydroxyurea improves glomerular filtration rate or reduces hyperfiltration in children aged nine to 18 months, but it may improve their ability to concentrate urine and may make little or no difference to the incidence of acute chest syndrome, painful crises, and hospitalisations. We are unsure if ACEI compared to placebo has any effect on preventing or reducing kidney complications in adults with normal blood pressure and microalbuminuria. We are unsure if ACEI compared to vitamin C has any effect on preventing or reducing kidney complications in children with normal blood pressure and microalbuminuria. No RCTs assessed red blood cell transfusions or any combined interventions to prevent or reduce kidney complications. Due to lack of evidence, we cannot comment on the management of children aged over 18 months or adults with any known genotype of SCD. We have identified a lack of adequately designed and powered studies, although we found four ongoing trials since the last version of this review. Only one ongoing trial addresses renal function as a primary outcome in the short term, but such interventions have long‐term effects. Trials of hydroxyurea, ACEIs or red blood cell transfusion in older children and adults are urgently needed to determine any effect on prevention or reduction of kidney complications in people with SCD

Pauvreté et accès à l'eau dans la vallée du Sénégal

Water poverty in the Senegal Valley Considering the flood-recession agriculture, the hydraulic history of the valley of the Senegal River is ancient, but knows a deep mutation since the introduction of the irrigation. Can one speak of water poverty, whereas two dams now control the water flow of the Senegal River and ensure a permanent abundance in water ? The answer to this questioning is proposed through the link between poverty, access to funding, access to land, and involvement in resource management.L'histoire hydraulique de la vallée du fleuve Sénégal est ancienne et remonte à la culture de décrue. Mais elle connaît une profonde mutation depuis l'introduction de l'irrigation. Peut-on parler de « pauvreté hydraulique », alors que deux barrages régulent à présent le régime du fleuve Sénégal et assurent une permanence de l'abondance en eau ? La réponse à cette question est proposée sous l'angle de l'articulation entre la pauvreté, l'accès au financement, l'accès au foncier, la participation à la gestion de la ressource

Pauvreté et accès à l'eau dans la vallée du Sénégal

L'histoire hydraulique de la vallée du fleuve Sénégal est ancienne et remonte à la culture de décrue. Mais elle connaît une profonde mutation depuis l'introduction de l'irrigation. Peut-on parler de « pauvreté hydraulique », alors que deux barrages régulent à présent le régime du fleuve Sénégal et assurent une permanence de l'abondance en eau ? La réponse à cette question est proposée sous l'angle de l'articulation entre la pauvreté, l'accès au financement, l'accès au foncier, la participation à la gestion de la ressource.HYDRAULIQUE ; HISTOIRE ; AMENAGEMENT HYDROAGRICOLE ; CULTURE DE DECRUE ; CULTURE IRRIGUEE ; SORGHO ; MIL ; RIZ IRRIGUE ; ACCES A LA TERRE ; RESSOURCES EN EAU ; GESTION DE L'ENVIRONNEMENT ; ACCES AU CREDIT ; TENURE FONCIERE ; ENDETTEMENT ; EXCLUSION SOCIALE ; PAUVRETE ; REVENUS AGRICOLES ; ORGANISATION PAYSANNE ; ACCES A L'EAU ; GESTION DE L'EAU ; SENEGAL ; FLEUVE SENEGAL VALLEE

Interaction-based quantum metrology showing scaling beyond the Heisenberg limit

Quantum metrology studies the use of entanglement and other quantum resources to improve precision measurement. An interferometer using N independent particles to measure a parameter X can achieve at best the "standard quantum limit" (SQL) of sensitivity {\delta}X \propto N^{-1/2}. The same interferometer using N entangled particles can achieve in principle the "Heisenberg limit" {\delta}X \propto N^{-1}, using exotic states. Recent theoretical work argues that interactions among particles may be a valuable resource for quantum metrology, allowing scaling beyond the Heisenberg limit. Specifically, a k-particle interaction will produce sensitivity {\delta}X \propto N^{-k} with appropriate entangled states and {\delta}X \propto N^{-(k-1/2)} even without entanglement. Here we demonstrate this "super-Heisenberg" scaling in a nonlinear, non-destructive measurement of the magnetisation of an atomic ensemble. We use fast optical nonlinearities to generate a pairwise photon-photon interaction (k = 2) while preserving quantum-noise-limited performance, to produce {\delta}X \propto N^{-3/2}. We observe super-Heisenberg scaling over two orders of magnitude in N, limited at large N by higher-order nonlinear effects, in good agreement with theory. For a measurement of limited duration, super-Heisenberg scaling allows the nonlinear measurement to overtake in sensitivity a comparable linear measurement with the same number of photons. In other scenarios, however, higher-order nonlinearities prevent this crossover from occurring, reflecting the subtle relationship of scaling to sensitivity in nonlinear systems. This work shows that inter-particle interactions can improve sensitivity in a quantum-limited measurement, and introduces a fundamentally new resource for quantum metrology

Topological semimetal in a fermionic optical lattice

Optical lattices play a versatile role in advancing our understanding of correlated quantum matter. The recent implementation of orbital degrees of freedom in chequerboard and hexagonal optical lattices opens up a new thrust towards discovering novel quantum states of matter, which have no prior analogs in solid state electronic materials. Here, we demonstrate that an exotic topological semimetal emerges as a parity-protected gapless state in the orbital bands of a two-dimensional fermionic optical lattice. The new quantum state is characterized by a parabolic band-degeneracy point with Berry flux $2\pi$, in sharp contrast to the $\pi$ flux of Dirac points as in graphene. We prove that the appearance of this topological liquid is universal for all lattices with D$_4$ point group symmetry as long as orbitals with opposite parities hybridize strongly with each other and the band degeneracy is protected by odd parity. Turning on inter-particle repulsive interactions, the system undergoes a phase transition to a topological insulator whose experimental signature includes chiral gapless domain-wall modes, reminiscent of quantum Hall edge states.Comment: 6 pages, 3 figures and Supplementary Informatio

Direct correction of haemoglobin E β-thalassaemia using base editors

Haemoglobin E (HbE) β-thalassaemia causes approximately 50% of all severe thalassaemia worldwide; equating to around 30,000 births per year. HbE β-thalassaemia is due to a point mutation in codon 26 of the human HBB gene on one allele (GAG; glutamatic acid → AAG; lysine, E26K), and any mutation causing severe β-thalassaemia on the other. When inherited together in compound heterozygosity these mutations can cause a severe thalassaemic phenotype. However, if only one allele is mutated individuals are carriers for the respective mutation and have an asymptomatic phenotype (β-thalassaemia trait). Here we describe a base editing strategy which corrects the HbE mutation either to wildtype (WT) or a normal variant haemoglobin (E26G) known as Hb Aubenas and thereby recreates the asymptomatic trait phenotype. We have achieved editing efficiencies in excess of 90% in primary human CD34 + cells. We demonstrate editing of long-term repopulating haematopoietic stem cells (LT-HSCs) using serial xenotransplantation in NSG mice. We have profiled the off-target effects using a combination of circularization for in vitro reporting of cleavage effects by sequencing (CIRCLE-seq) and deep targeted capture and have developed machine-learning based methods to predict functional effects of candidate off-target mutations

Gravitino Dark Matter in Tree Level Gauge Mediation with and without R-parity

We investigate the cosmological aspects of Tree Level Gauge Mediation, a recently proposed mechanism in which the breaking of supersymmetry is communicated to the soft scalar masses by extra gauge interactions at the tree level. Embedding the mechanism in a Grand Unified Theory and requiring the observability of sfermion masses at the Large Hadron Collider, it follows that the Lightest Supersymmetric Particle is a gravitino with a mass of the order of 10 GeV. The analysis in the presence of R-parity shows that a typical Tree Level Gauge Mediation spectrum leads to an overabundance of the Dark Matter relic density and a tension with the constraints from Big Bang Nucleosynthesis. This suggests to relax the exact conservation of the R-parity. The underlying SO(10) Grand Unified Theory together with the bounds from proton decay provide a rationale for considering only bilinear R-parity violating operators. We finally analyze the cosmological implications of this setup by identifying the phenomenologically viable regions of the parameter space.Comment: 28 pages, 5 figures. References added. To appear in JHE

Effect of cyclosporine on hepatic cytosolic estrogen and androgen receptor levels before and after partial hepatectomy

Estrogen and androgen receptors within the liver have been reported to modulate the hepatic regenerative response to partial hepatectomy. Moreover, cyclosporine has several untoward effects that might occur as a consequence of alterations in sex hormone activity. To evaluate these questions the following experiments were performed. Estrogen and androgen receptors in cytosol were quantitated in livers of rats treated with cyclosporine or olive oil vehicle before and after partial hepatectomy or a sham operation. Ornithine decarboxylase activity and thymidine kinase activity were assessed as indices of hepatic regeneration. Preoperative levels of estrogen receptor activity in the hepatic cytosol were significantly greater in rats treated with cyclosporine as compared to vehicle treated controls (P<0.01). In contrast, preoperative levels of androgen receptor activity in the cyclosporine-treated and vehicle-treated animals were similar. Following partial hepatectomy, a reduction in the activity of both sex hormone receptors in the hepatic cytosol was observed and was compatible with results described previously in normal animals. Unexpectedly the preoperative levels of ornithine decarboxylase (P<0.01) and thymidine kinase activity (P<0.01) were significantly greater in the rats treated with cyclosporine as compared to the vehicle treated controls. As expected, ornithine decarboxylase activity (at 6 hr) and thymidine kinase activity (at 24 hr) rose and peaked in response to a partial hepatectomy but were significantly greater (P<0.05) in the rats treated with cyclosporine as compared to the vehicle. These results show that cyclosporine treatment causes an increase in the hepatic content of estrogen receptor activity that is associated with an enhanced potential for a regenerative response. These effects of cyclosporine treatment on the sex hormone receptor levels in liver may explain the mechanisms responsible for some of the untoward effects of treatment with this agent. © 1990 Plenum Publishing Corporation