Glacial isostatic adjustment directed incision of the Channeled Scabland by Ice Age megafloods.

During the last deglaciation, dozens of glacial outburst floods-among the largest known floods on Earth-scoured the Channeled Scabland landscape of eastern Washington. Over this same period, deformation of the Earth's crust in response to the growth and decay of ice sheets changed the topography by hundreds of meters. Here, we investigated whether glacial isostatic adjustment affected routing of the Missoula floods and incision of the Channeled Scabland from an impounded, glacial Lake Columbia. We used modern topography corrected for glacial isostatic adjustment as an input to flood models that solved the depth-averaged, shallow water equations and compared the results to erosion constraints. Results showed that floods could have traversed and eroded parts of two major tracts of the Channeled Scabland-Telford-Crab Creek and Cheney-Palouse-near 18 ka, whereas glacial isostatic adjustment limited flow into the Cheney-Palouse tract at 15.5 ka. Partitioning of flow between tracts was governed by tilting of the landscape, which affected the filling and overspill of glacial Lake Columbia directly upstream of the tracts. These results highlight the impact of glacial isostatic adjustment on megaflood routing and landscape evolution.

Social determinants of health in uterine carcinosarcoma.

OBJECTIVE: UCS survival outcome disparities by race have been reported. We aimed to investigate social determinants of health (SDOH) and their relation to survival outcomes in women at two affiliated high-volume institutions serving a racially and economically diverse population. METHODS: Women diagnosed with stage I-IV UCS treated at St. Paul University Hospital, University of Texas Southwestern (UTSW) Zale Lipshy Pavilion-William P. Clements Jr. University Hospital, and Parkland Memorial Hospital between 1992 and 2022 were eligible. Patients were identified by the local tumor registries; a retrospective study was conducted. The Pearson chi-square test was utilized for categorical variables. OS and PFS were calculated using Kaplan-Meier estimates and compared with the log-rank test. Multivariate Cox models were used to identify independent prognostic factors. All statistical analyses were performed using SAS, version 9.4. RESULTS: Over half of the 218 patients with UCS were NHB. 35% of the patients had stage IV disease. Most HSP and NHB patients had a lower median household income* than Asian/Pacific Islander (API) or NHW (p < 0.001). Stage at diagnosis significantly affected OS (p < 0.001) but not PFS (p = 0.46) in univariate analyses. Accounting for age at diagnosis, insurance, income*, hospital, distance between hospital and home, months from diagnosis to first treatment, stage, and adjuvant therapy, race was significant for OS (p = 0.03) and PFS (p = 0.04). *Median household income by ZIP Code. CONCLUSIONS: Racial disparities were seen in median household income. Most SDOH independently analyzed in this study did not affect OS. The complex interaction between race and stage in UCS survival outcomes needs further investigation.

Examining the Intersection of Ethnoracial Disparities and HIV Status in Substance Use Risks among U.S. Adults.

Black/African American and Hispanic Americans experience significant HIV-related disparities. Substance use might be a contributing factor to these disparities, but there is limited research on this topic. This study investigated various substance use risks by HIV status and race/ethnicity (Black, Hispanic, White) among U.S. adults. We used data from the 2005-2019 National Survey on Drug Use and Health (N = 541,921). In each racial/ethnic group, the prevalence rates of past-year and past-month tobacco, alcohol, cannabis, and cocaine use, and past-year alcohol and illicit drug use disorders were estimated by HIV status. A series of logistic regressions with the interaction term of HIV x race/ethnicity were performed to examine race/ethnicity's moderating effect on the HIV-substance use associations, while controlling for sociodemographic factors and survey year. Moderation analysis showed that HIV status's association with the risks of past-year tobacco use (AOR = 1.67, 95% CI = 1.01-2.75), past-year cocaine use (AOR = 3.80, 95% CI = 1.91-7.57), past-month cocaine use (AOR = 5.34, 95% CI = 2.10-13.60), and past-year alcohol use disorder (AOR = 2.52, 95% CI = 1.29-4.92) differed significantly between Black and White adults. Between the Hispanic and White groups, HIV status's association with the risks of past-year alcohol use (AOR = 2.00, 95% CI = 1.09-3.69), past-year cocaine use (AOR = 2.40, 95% CI = 1.06-5.39), and past-month cocaine use (AOR = 3.69, 95% CI = 1.36-10.02) also differed significantly. It is well-established that individuals with HIV face an elevated risk of substance use. Our study added valuable insights by highlighting that this phenomenon is particularly more significant among Black and Hispanic adults for several substances when compared to White adults. Implications for practice are discussed.

Six-year cumulative treatment effect and treatment efficacy of a dual focus myopia control contact lens.

PURPOSE: Accumulated axial growth observed during a 6-year clinical trial of a dual focus myopia control contact lens was used to explore different approaches to assess treatment efficacy. METHODS: Axial length measurements from 170 eyes in a 6-year clinical trial of a dual focus myopia control lens (MiSight 1 day, CooperVision) were analysed. Treatment groups comprised one having undergone 6 years of treatment and the other (the initial control group) having 3 years of treatment after 3 years of wearing a single vision control lens. Efficacy was assessed by comparing accumulated ocular growth during treatment to that expected of untreated myopic and emmetropic eyes. The impact of treatment on delaying axial growth was quantified by comparing the increased time required to reach criterion growths for treated eyes and survivor analysis approaches. RESULTS: When compared to the predicted accumulated growth of untreated eyes, 6 years of treatment reduced growth by 0.52 mm, while 3 years of treatment initiated 3 years later reduced growth by 0.19 mm. Accumulated differences between the growth of treated and untreated myopic eyes ranged between 67% and 52% of the untreated myopic growth, and between 112% and 86% of the predicted difference in growth between untreated myopic and age-matched emmetropic eyes. Treated eyes took almost 4 years longer to reach their final accumulated growth than untreated eyes. Treatment increased the time to reach criterion growths by 2.3-2.7 times. CONCLUSION: Estimated growth of age-matched emmetropic and untreated myopic eyes provided evidence of an accumulated slowing in axial elongation of 0.52 mm over 6 years, and the treated growth remained close to that expected of emmetropic eyes. Six years of dual focus myopia control delayed the time to reach the final growth level by almost 4 years.

From Scan to Simulation-A Novel Workflow for Developing Bioinspired Heart Valves.

Current heart valve replacements lack durability and prolonged performance, especially in pediatric patients. In part, these problems may be attributed to the materials chosen for these constructs, but another important contributing factor is the design of the valve, as this dictates hemodynamic performance and impacts leaflet stresses which may accelerate structural valve deterioration. Most current era bioprosthetic valves adhere to a fundamental design where flat leaflets are supported by commissural posts, secured to a sewing ring. This overall design strategy is effective, but functionality and durability can be improved by incorporating features of the native valve geometry. This paper presents a novel workflow for developing and analyzing bio-inspired valve designs computationally. The leaflet curvature was defined using a mathematical equation whose parameters were derived from the three-dimensional model of a native sheep pulmonary valve obtained via microcomputed tomography. Finite element analysis was used to screen the various valve designs proposed in this study by assessing the effect of leaflet thickness, Young's modulus, and height/curvature on snap-through (where leaflets bend against their original curvature), geometric orifice area (GOA) and the stress in the leaflets. This workflow demonstrated benefits for valve designs with leaflet thicknesses between 0.1 and 0.3 mm, Young's moduli less than 50 MPa, and elongated leaflets with higher curvatures. The proposed workflow brings substantial efficiency gains at the design stage, minimizing manufacturing and animal testing during iterative improvements, and offers a bridge between in vitro and more complex in silico studies in the future.

Impact of baseline renal dysfunction on cardiac outcomes and end-stage renal disease in heart failure patients with mitral regurgitation: the COAPT trial.

AIMS: Baseline renal dysfunction (RD) adversely impacts outcomes among patients with heart failure (HF) and severe secondary mitral regurgitation (MR). Heart failure and MR, in turn, accelerate progression to end-stage renal disease (ESRD), worsening prognosis. We sought to determine the impact of RD in HF patients with severe MR and the impact of transcatheter mitral valve repair (TMVr) on new-onset ESRD and the need for renal replacement therapy (RRT). METHODS AND RESULTS: The COAPT trial randomized 614 patients with HF and severe MR to MitraClip plus guideline-directed medical therapy (GDMT) vs. GDMT alone. Patients were stratified into three RD subgroups based on baseline estimated glomerular filtration rate (eGFR, mL/min/1.73 m2): none (≥60), moderate (30-60), and severe (<30). End-stage renal disease was defined as eGFR <15 mL/min/1.73 m2 or RRT. The 2-year rates of all-cause death or HF hospitalization (HFH), new-onset ESRD, and RRT according to RD and treatment were assessed. Baseline RD was present in 77.0% of patients, including 23.8% severe RD, 6.0% ESRD, and 5.2% RRT. Worse RD was associated with greater 2-year risk of death or HFH (none 45.3%; moderate 53.9%; severe 69.2%; P < 0.0001). MitraClip vs. GDMT alone improved outcomes regardless of RD (Pinteraction = 0.62) and reduced new-onset ESRD [2.9 vs. 8.1%, hazard ratio (HR) 0.34, 95% confidence interval (CI) 0.15-0.76, P = 0.008] and the need for new RRT (2.5 vs. 7.4%, HR 0.33, 95% CI 0.14-0.78, P = 0.011). CONCLUSION: Baseline RD was common in the HF patients with severe MR enrolled in COAPT and strongly predicted 2-year death and HFH. MitraClip treatment reduced new-onset ESRD and the need for RRT, contributing to the improved prognosis after TMVr.

The Sulfur Rich Fluorothiophosphate Dianions [S5 P2 F2 ]2- and [S3 PF]2- : Cluster and Chelation Control of P-S Heterolysis.

The sulfur rich difluoropentathiodiphosphate dianion [S5 P2 F2 ]2- , from fluoride addition to P4 S10 , has a somewhat checkered history and proves to be the main product of the reaction in acetonitrile. Its optimized synthesis, and structural characterization, as either a tetraphenylphosphonium or a tetrapropylammonium salt, [Nn Pr4 ]2 [S5 P2 F2 ] allows for the first coordination chemistry for this dianion. Reactions of [S5 P2 F2 ]2- with d10 metal ions of zinc(II), and cadmium(II), and d9 copper(II) resulted in a surprising diverse array of binding modes and structural motifs. In addition to the simple bis-chelate coordination of [S5 P2 F2 ]2- with zinc, cleavage of the P-S bond resulted in complexes with the unusual [S3 PF]2- fluorotrithiophosphate dianion. This was observed in two cluster complexes: a trinuclear cadmium complex with mixed [S5 P2 F2 ]2- /[S3 PF]2- ligands, [Cd3 (S5 P2 F2 )3 (S3 PF)2 ]4- as well as an octanuclear copper cluster, [Cu8 (S3 PF)6 ]4- which form rapidly at room temperature. These new metal/sulfur/ligand clusters are of relevance to understanding multimetal binding to metallothionines, and to potential capping strategies for the condensed nanoparticulate cadmium chalcogenide semiconductors CdS and CdSe.

Transcatheter mitral valve repair in patient with atrial functional mitral regurgitation using novel DragonFly™ device.

We report the first case of transcatheter mitral valve repair with the novel DragonFly™ device, a transcatheter edge-to-edge mitral regurgitation (MR) repair device, in a patient with severe, symptomatic MR due to annular dilation from atrial functional disease (Carpentier type I). The patient had experienced multiple heart failure events and was unsuitable for surgery due to pulmonary dysfunction and obesity.

Transcatheter mitral valve repair in a high-surgical risk patient with severe degenerative mitral regurgitation using the novel DragonFly™ Transcatheter Repair device-First in man implantation in China.

Transcatheter repair of mitral regurgitation (MR) by edge-to-edge therapy has become increasingly accepted for patients with severe MR at high or prohibitive surgical risk in primary or degenerative mitral regurgitation (DMR). The technological approach has evolved from the initial transcatheter edge-to-edge device to improve on its acute reduction in MR and durability of results, particularly in complex primary pathology. In this study, we reported the first case of DragonFly™ Transcatheter Valve Repair device in a patient with severe DMR.

Fluorotrithiophosphate Abstraction from the Difluoropentathiodiphosphate Dianion: d8 and d6 Complexes of [η2-S3PF]2.

Coordinative heterolysis of the difluoropentathiodiphosphate dianion [S5P2F2]2- results in the formal elimination of [S2PF] by complexes of the group 10 divalent metals nickel, palladium, and platinum. The remaining fragment of this cleavage, [S3PF]2- coordinates as an η2-ligand. Several complexes with this novel fluorotrithiophosphate were characterized structurally and spectroscopically with X-ray diffraction (XRD), infrared (IR) spectroscopy, and 31P and 19F nuclear magnetic resonance (NMR). In addition to mononuclear η2 chelate complexes, bridging complexes with η2-µ2-S3PF configurations result in binuclear nickel and ruthenium adducts. Facile methylation with methyl triflate of the uncoordinated sulfur atom leads to a complex with the methylthiofluorodithiophosphate ligand in a cationic complex, which hydrolyses with loss of fluoride to give complexed [S2P(O)SMe]2-. Alternatively hydrolysis can also lead to a binuclear Ni2(dppe)2(S3PF)(S2POF) complex. Divalent ruthenium π-aryl's form fluorotrithiophosphate complexes rapidly at room temperature to give bridged dimers with complete chloride substitution.

Emerging directions of cognitive aging with HIV: practice and policy implications for social work.

Cognitive impairments have been endemic to the HIV epidemic since its beginning and persist to this day. These impairments are attributed to HIV-induced neuroinflammation, the long-term effects of combination antiretroviral therapy, lifestyle factors (e.g., sedentary behavior, substance use), neuro-comorbidities (e.g., depression), age-associated comorbidities (e.g., heart disease, hypertension), and others causes. Normal aging and lifestyle also contribute to the development of cognitive impairment. Regardless of the etiology, such cognitive impairments interfere with HIV care (e.g., medication adherence) and everyday functioning (e.g., driving safely, financial management). With more than half of people with HIV (PWH) 50 years and older, and ~45% of all PWH meeting the criteria for HIV-Associated Neurocognitive Disorder (HAND), those aging PWH are more vulnerable for developing cognitive impairment. This article provides an update to a social work model to identify and monitor PWH for cognitive impairment. Within this update, the state of the science on protecting brain health and cognitive reserve within the context of neuroHIV is also presented. From this, implications for practice and policy to promote successful cognitive functioning in older PWH are provided.

Separation of Isomers and Mechanisms of Inversion of Stereochemistry of Group 9 d6 Tris-Chelate Complexes of Hinokitiol.

Tris-chelate complexes of Co(III), Rh(III), and Ir(III) with 4-isopropyltropolone (hinokitiol or ß-thujaplicin) form by the substitution of carbonate and chloride ligands from group 9 trivalent metal salts. The new complexes are neutral, are readily soluble in most organic solvents, and are brightly colored with strong charge transfer bands. The fac isomers of Co(hino)3 and Rh(hino)3 were isolated from the mixture by fractional recrystallization from ethanol. The remaining mixtures were respectively enriched by 5:3 and 4.4:3 for the mer isomer. The 1H NMR data show that the complexes exhibit remarkable stereochemical lability, which is unusual for diamagnetic d6 group 9 metals, with rotational barriers of 14.2 and 18.2 kcal/mol found for the inversion of stereochemistry of Co(hino)3 and Rh(hino)3. The low activation barriers, as well as the analysis of some key structural parameters, suggest that the inversion of stereochemistry occurs via a trigonal-twist (Bailar) mechanism. Facile substitution of a single hinokitiol ligand in the cobalt complex with ethylenediamine to form [Co(en)(hino)2]Cl also indicates that the tris-chelates are substitutionally and configurationally labile.

Fluxionality in the Tropolone Hinokitiol Chelate.

Tropolonate complexes of Ru(II), Ru(III), and Os(II) with hinokitiol, also termed ß-thuljaplicin, or 4-isopropyltropolone, readily formed by chloride and triarylphosphine substitution in RuCl2(PPh3)3 and MHCl(CO)(PR3)3 (M = Ru, R = Ph; M = Os, R = Ph and p-tolyl). The resulting colorful complexes have variable and strong charge transfer bands and also have a surprising combination of stereochemical selectivity and lability. For the Os(II) d6 examples, the tropolone chelate has a fluxionality with a barrier of only 90 kJ/mol for the R = aryl examples, as determined by variable-temperature 31P NMR. Chlorination with N-chlorosuccinimide results in MCl(CO)(hino)(PPh3)2 (M = Ru and Os). Together these results quantify the fluxionality of this important chelate which in turn has consequences for its biochemistry.

Stage IVA cervical cancer: outcomes of disease related complications and treatment.

INTRODUCTION: Stage IVA cervical cancer is an uncommon diagnosis. The course of the disease and the complications of treatment are not well characterized. The goal of this study was to report treatment outcomes of patients with stage IVA cervical cancer. METHODS: A single institution retrospective review was carried out of all patients treated for stage IVA cervical cancer from January 2008 to July 2017. Patients were clinically staged using the International Federation of Gynecology and Obstetrics (FIGO) 2009 staging criteria for cervical cancer. Inclusion criteria were patients with stage IVA cervical cancer of any histologic subtype, including patients with evidence of para-aortic lymph node involvement, treated at the institution during this time period. Overall survival and progression free survival were calculated using the Kaplan-Meyer method. Comparisons between survival were done using the Cox proportional hazards regression model and the log rank test. RESULTS: We identified 25 patients with stage IVA cervical cancer. Mean age at diagnosis was 54 years (range 27-77). Squamous cell carcinoma was the histologic diagnosis in 24 of 25 patients (96%), with 1 case of small cell carcinoma (4%). 21 patients completed a full course of radiation. The median overall survival for patients who completed their treatment was 60 months (range 3-136), with a 2 year overall survival of 63%. The median progression free survival was 27 months (range 0-125), with a 2 year progression free survival of 40%. 11 of 25 patients (44%) developed fistulas during the course of their disease, and 55% of these were complex fistulas. 19 of 25 (76%) patients had a percutaneous nephrostomy for either hydronephrosis or diversion of vesicovaginal fistula. 111 unplanned admissions occurred among the 25 patients, and infections of the urinary tract was implicated in 46 (41%) of these. The cohort had a total of 92 emergency department visits, with pain control (36%) and medication refills (15%) being the most common presentations. DISCUSSION: Patients with stage IVA cervical cancer may have substantial long term survival, although the sequelae of disease and treatment is associated with significant morbidity. Symptoms of fistula, percutaneous nephrostomy complications, and chronic pain present unique issues that require extensive supportive care.

Pilot trial of a mouthpiece as treatment for signs and symptoms of Parkinson disease.

PURPOSE: Several case studies and anecdotal reports have shown assorted motor and quality of life benefits from use of a dental mouthpiece among people with Parkinson disease (PD). A larger exploratory study is necessary to assess potential efficacy and feasibility of this treatment strategy. If shown to be effective and feasible in a larger sample of people with PD, mechanistic studies may be warranted to examine a potential relationship between orofacial sensory input and motor function in people with PD. MATERIALS AND METHODS: This study was registered on clinicaltrials.gov (NCT: 04082663). Twenty people with PD, Hoehn and Yahr stages I-III, participated in this study. Each participant completed various baseline motor and quality of life assessments before being fitted with a custom mouthpiece. Motor assessments were completed a second time after 25 min of mouthpiece wear. Participants were asked to wear the mouthpiece for 1 month before completing follow-up quality of life assessments and providing feedback about the mouthpiece. Wilcoxon signed-rank tests were used to compare results across conditions. RESULTS: Gait velocity and cadence showed significant (p < .05) improvement while wearing the mouthpiece. However, these changes were not significant after correcting for multiple comparisons. Thirteen participants indicated they would be unlikely to continue wearing the mouthpiece. CONCLUSIONS: These results do not provide adequate evidence to pursue further this type of mouthpiece as a treatment strategy for motor signs and symptoms or quality of life in people with PD.

Prevalence, Characteristics, and Impact of Frailty in Patients with Functional Tricuspid Regurgitation.

Little is known as regards frailty in patients with functional tricuspid regurgitation (FTR). Thus, in this study, we aimed to investigate the prevalence, characteristics, and impact of frailty on patients with severe FTR.This prospective study included 110 consecutive patients with severe FTR who were assessed via transthoracic echocardiography at an outpatient clinic. Patients were dichotomized using short physical performance battery (SPPB). To better understand the whole picture of frailty in patients with FTR, other frailty scales were also assessed (frailty checklist, clinical frailty scale, gait speed, and Columbia frailty scale). The primary endpoint was the combination of all-cause mortality and heart failure hospitalization.According to each definition of frailty, 28%-46% were identified to be frail. Those with SPPB score of < 9 were older, had greater New York Heart Association (NYHA) functional classification, and had lower albumin level and estimated glomerular filtration rate compared with those with SPPB score of ≥ 9. They also have smaller tricuspid valve coaptation depth and worse right ventricular fractional area change (RV-FAC) than those with SPPB score of ≥ 9 despite having similar TR severity. The primary endpoint at 1 year was noted in 31% of patients. The SPPB score has excellent discriminatory performance for predicting the primary endpoint (area under the curve 0.82, 95% confidence interval [CI] 0.76-0.91) in receiver operating characteristic analysis and was independently associated with the primary endpoint after adjustment in multivariate analysis (adjusted hazard ratio 0.81, 95% CI, 0.73-0.90; P < 0.001).Frailty has been widely prevalent in the elderly patient population with FTR; in fact, it has been determined to be strong parameter for poor outcomes.

Progress in endometrial cancer: Contributions of the former Gynecologic Oncology Group.

For over forty years, the Gynecologic Oncology Group drove progress in treating endometrial cancer. The first decades of investigation began with a meticulous prospective, surgicopathologic staging study that was the platform for development of all subsequent trials. The resultant statistical model of low risk, intermediate risk, and high-risk groups of patients led to trials where therapeutic modalities were best targeted at disease spread. A clear role for chemotherapy was established. It was realized that greater advances might be achieved with the advent of newer anti-neoplastic agents and these agents were subjected to extensive phase II testing. These agents later were integrated into comparison trials for advanced endometrial cancer. Multimodality therapy continues to show promise. Hormonal therapy was thoroughly investigated and led to combination hormonal therapy trials. Newer agents, including biologics are under active study, as well as the potential contribution of modern imaging techniques. Finally, GOG0210 established a repository of clinical specimens with detailed clinical and epidemiologic data from patients with surgically staged endometrial carcinoma. This should provide for a much greater understanding of molecular characteristics associated with risk of endometrial cancer recurrence, clinical and histological characteristics, and epidemiologic factors.

Nursing students' engagement and experiences with virtual reality in an undergraduate bioscience course.

Objectives The challenges of bioscience courses such as anatomy and physiology in nursing education are well documented. Virtual reality has recently become accessible and may support student engagement. The purpose of this project was to describe students' engagement and experiences with virtual reality in a first-year nursing course on anatomy, physiology, and health assessment. Methods We used a cross-sectional design and collected both quantitative and qualitative data. The Exploratory Learning Model guided our work. Results Students perceived their engagement to be higher in virtual reality compared to other teaching methods. Their experiences were positive with students reporting that they found it easy to use, it helped their learning, and they recommended more of it. Conclusions Virtual reality is an accessible tool for supporting student engagement. The Exploratory Learning Model is a useful conceptualization for integrating virtual reality into a course. Future research on the relationship between virtual reality and learning achievements is warranted.

Niraparib monotherapy for late-line treatment of ovarian cancer (QUADRA): a multicentre, open-label, single-arm, phase 2 trial.

BACKGROUND: Late-line treatment options for patients with ovarian cancer are few, with the proportion of patients achieving an overall response typically less than 10%, and median overall survival after third-line therapy of 5-9 months. In this study (QUADRA), we investigated the activity of niraparib monotherapy as the fourth or later line of therapy. METHODS: QUADRA was a multicentre, open-label, single-arm, phase 2 study that evaluated the safety and activity of niraparib in adult patients (≥18 years) with relapsed, high-grade serous (grade 2 or 3) epithelial ovarian, fallopian tube, or primary peritoneal cancer who had been treated with three or more previous chemotherapy regimens. The study was done in the USA and Canada, and 56 sites screened patients (50 sites treated at least one patient). Patients received oral niraparib 300 mg once daily continuously, beginning on day 1 and every cycle (28 days) thereafter until disease progression. The primary objective was the proportion of patients achieving an investigator-assessed confirmed overall response in patients with homologous recombination deficiency (HRD)-positive tumours (including patients with BRCA and without BRCA mutations) sensitive to their last platinum-based therapy who had received three or four previous anticancer therapy regimens (primary efficacy population). Efficacy analyses were additionally done in all dosed patients with measurable disease at baseline. FINDINGS: Between April 1, 2015 and Nov 1, 2017, we screened 729 patients for eligibility and enrolled 463 patients, who were initiated on niraparib therapy. At the time of database lock (April 11, 2018), enrolment had closed and the study was ongoing, with 21 patients still on treatment. Patients had received a median of four (IQR 3-5) previous lines of therapy, and the median follow-up for overall survival was 12·2 months (IQR 3·7-22·1). 151 (33%) of 463 patients were resistant and 161 (35%) of 463 patients were refractory to the last administered platinum therapy. 13 (28%) of 47 patients in the primary efficacy population achieved an overall response according to RECIST (95% CI 15·6-42·6; one-sided p=0·00053). The most common drug-related grade 3 or worse treatment-emergent adverse events were anaemia (113 [24%] of 463 patients) and thrombocytopenia (95 [21%] of 463 patients). The most common treatment-emergent serious adverse events were small intestinal obstruction (34 [7%] of 463 patients), thrombocytopenia (34 [7%] of 463 patients), and vomiting (27 [6%] of 463 patients). One death due to gastric haemorrhage was considered treatment related. INTERPRETATION: We observed clinically relevant activity of niraparib among women with heavily pretreated ovarian cancer, especially in patients with HRD-positive platinum-sensitive disease, which includes not only patients with a BRCA mutation but also a population with BRCA wild-type disease. We identified no new safety signals. Our data support expansion of the treatment indication for poly(ADP-ribose) polymerase inhibitors to include patients with HRD-positive ovarian cancer beyond those with BRCA mutations. FUNDING: Tesaro.

Congenital hydrocephalus in a Belgian draft horse associated with a nonsense mutation in B3GALNT2.

Congenital hydrocephalus has been reported for a number of horse breeds, and for Friesian horses this condition has been associated with a nonsense mutation of B3GALNT2. We report the first case of congenital hydrocephalus associated with the said mutation in a Belgian draft horse. Genetic testing and consideration of the testing results in breeding programs are warranted.

Hydrocéphalie congénitale chez un cheval de trait Belge associée à une mutation non-sens de B3GALNT2. L'hydrocéphalie congénitale a été signalée pour plusieurs races de chevaux et, pour les chevaux Frisons, cette affection a été associée à une mutation non-sens de B3GALNT2. Nous signalons le premier cas d'hydrocéphalie congénitale associée à cette mutation chez un cheval de trait Belge. Les tests génétiques et la considération des résultats des tests sont justifiés dans le cadre des programmes d'élevage.(Traduit par Isabelle Vallières).