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Ice streams flowing into Ross Ice Shelf are presently responsible for around 10% of the mass flux from West Antarctica, with the noteworthy exception of Kamb Ice Stream, which stagnated in the late 1800s. The subsequent reduction in ice supply led to grounding-line retreat at the coastal margin where Kamb transitions into the floating Ross Ice Shelf. Grounding-line migration is linked to broader changes in ice-sheet mass balance and sea level, but our understanding of related ice, ocean and seafloor interactions is limited by the difficulty in accessing these remote regions. Here we report in situ observations from an underwater vehicle deployed at Kamb that show how fine-scale variability in ice and ocean structure combine to influence a diversity of ice–ocean interactions. We found a stratified water column within a tenth of a degree of freezing at the ice base and mapped basal crevasses with supercooled water and active marine ice formation. At the seafloor, we interpret parallel ridges as crevasse impressions left as the ice lifted off during grounding-line retreat. These observations from a recently ungrounded sub-shelf environment illuminate both the geomorphological signatures of past grounding-line retreat and the fine-scale sensitivity of ongoing ice–ocean interactions to ice topography.

Expansion duraplasty to reopen effaced subarachnoid space and improve spinal cord perfusion, autoregulation, and spinal pressure reactivity index (sPRX) has been advocated in patients with traumatic cervical spinal cord injury (tCSCI). We designed this study to identify candidates for expansion duraplasty, based on the absence of cerebrospinal fluid (CSF) interface around the spinal cord on magnetic resonance imaging (MRI), in the setting of otherwise adequate bony decompression. Over a 61-month period, 104 consecutive American Spinal Injury Association Impairment Scale (AIS) grades A-C patients with tCSCI had post-operative MRI to assess the adequacy of surgical decompression. Their mean age was 53.4 years, and 89% were male. Sixty-one patients had falls, 31 motor vehicle collisions, 11 sport injuries, and one an assault. The AIS grade was A in 56, B in 18, and C in 30 patients. Fifty-four patients had fracture dislocations; there was no evidence of skeletal injury in 50 patients. Mean intramedullary lesion length (IMLL) was 46.9 (standard deviation = 19.4) mm. Median time from injury to decompression was 17 h (interquartile range 15.2 h). After surgery, 94 patients had adequate decompression as judged by the presence of CSF anterior and posterior to the spinal cord, whereas 10 patients had effacement of the subarachnoid space at the injury epicenter. In two patients whose decompression was not definitive and post-operative MRI indicated inadequate decompression, expansion duraplasty was performed. Candidates for expansion duraplasty (i.e., those with inadequate decompression) were significantly younger (

BACKGROUND: Women with urgency/frequency predominant lower urinary tract symptoms (UF-LUTS) may have elevated pelvic floor muscle (PFM) position at rest and limited mobility with PFM contraction and bearing down, but this has not been quantified. OBJECTIVES: To compare PFM position and mobility using transperineal ultrasound (TPUS) at rest, maximal PFM contraction (perineal elevation), and bearing down (perineal descent) in women with and without UF-LUTS. We hypothesized that women with UF-LUTS would demonstrate elevated resting position and decreased excursion of pelvic landmarks during contraction and bearing down as compared to women without UF-LUTS. STUDY DESIGN: Case-control study METHODS: Women with UF-LUTS were matched 1:1 on age, body mass index and vaginal parity to women without UF-LUTS. TPUS videos were obtained during 3 conditions: rest, PFM contraction, and bearing down. Levator plate angle (LPA) and puborectalis length (PR length), were measured for each condition. Paired t-tests or Wilcoxon signed rank tests compared LPA and PR length between cases and controls. RESULTS: 21 case-control pairs (42 women): Women with UF-LUTS demonstrated greater LPA at rest (66.8 ± 13.2 degrees vs 54.9 ± 9.8 degrees; P=0.006), and less PR lengthening from rest to bearing down (0.2 ± 3.1 mm vs 2.1 ± 2.9 mm; P=.03). CONCLUSION: Women with UF-LUTS demonstrated more elevated (cranioventral) position of the PFM at rest and less PR muscle lengthening with bearing down. These findings highlight the importance of a comprehensive PFM examination and possible treatment for women with UF-LUTS to include PFM position and mobility.

Thwaites Glacier represents 15% of the ice discharge from the West Antarctic Ice Sheet and influences a wider catchment1–3. Because it is grounded below sea level4,5, Thwaites Glacier is thought to be susceptible to runaway retreat triggered at the grounding line (GL) at which the glacier reaches the ocean6,7. Recent ice-flow acceleration2,8 and retreat of the ice front8–10 and GL11,12 indicate that ice loss will continue. The relative impacts of mechanisms underlying recent retreat are however uncertain. Here we show sustained GL retreat from at least 2011 to 2020 and resolve mechanisms of ice-shelf melt at the submetre scale. Our conclusions are based on observations of the Thwaites Eastern Ice Shelf (TEIS) from an underwater vehicle, extending from the GL to 3 km oceanward and from the ice–ocean interface to the sea floor. These observations show a rough ice base above a sea floor sloping upward towards the GL and an ocean cavity in which the warmest water exceeds 2 °C above freezing. Data closest to the ice base show that enhanced melting occurs along sloped surfaces that initiate near the GL and evolve into steep-sided terraces. This pronounced melting along steep ice faces, including in crevasses, produces stratification that suppresses melt along flat interfaces. These data imply that slope-dependent melting sculpts the ice base and acts as an important response to ocean warming.

Objective The objective of this study was to determine factors associated with performance of concomitant apical support procedures (ASPs) with benign hysterectomy at a regional medical system. Methods Benign hysterectomies performed within 1 regional medical system from January 2011 to November 2017 were identified using International Classification of Diseases, Ninth and 10th Revision, and Current Procedural Terminology codes. Primary outcome was performance of concomitant ASP. χ2 Tests compared categorical variables. Multivariable logistic regression analysis was performed to determine factors associated with performance of concomitant ASP. Results A total of 12,345 benign hysterectomies were performed during the study period. Uterovaginal prolapse was the primary diagnosis in 924 (7.48%) hysterectomies and an associated diagnosis in 1180 (9.56%) hysterectomies. A total of 686 patients (5.56%) had concurrent ASPs: 119 (17.3%) in patients without a diagnosis of prolapse and 567 (82.7%) with prolapse. Using multivariable logistic regression, controlling for age, race, insurance type, hospital type, procedure year, hysterectomy route, and surgeon training in patients with a diagnosis of prolapse, older age, supracervical hysterectomy, and surgeon training were associated with performance of ASPs. Conclusions Even in patients with a preoperative diagnosis of uterovaginal prolapse, ASPs are not routinely performed at time of hysterectomy. Fellowship-trained surgeons were more likely to perform ASPs. Ongoing educational efforts during training and postgraduate at the national and regional level on the importance of reestablishing apical vaginal support at time of hysterectomy is needed to prevent incident and recurrent post-hysterectomy vaginal vault prolapse.

OBJECTIVES: Vaginal estrogen therapy has been shown to decrease the risk of recurrent urinary tract infections in postmenopausal women, but the mechanism of action has not been fully described. Our objectives were to assess whether the postmenopausal urine inflammatory profile changes in response to vaginal estrogen therapy. METHODS: We prospectively enrolled postmenopausal patients into three groups: 1) currently using vaginal estrogen therapy without a history of recurrent urinary tract infections; 2) history of urinary tract infections, currently using vaginal estrogen therapy; and 3) history of recurrent urinary tract infections, not using vaginal estrogen therapy but willing to start. We followed patients over 6–19 months and collected urine samples at three time points. We performed comprehensive cytopathologic analysis, quantitative urine inflammatory scoring, and enzyme-linked immunosorbent assay for IL-6. RESULTS: Seventy patients were recruited (Group 1, n=30; Group 2, n=20; Group 3, n=20). Urine from patients in Groups 2 and 3 demonstrated increased inflammatory cells, debris, and exfoliated urothelial cells. Quantitative urine inflammatory scores and IL-6 were significantly higher in postmenopausal patients with recurrent urinary tract infections not on vaginal estrogen therapy (0.12 vs 0.93, p

Introduction Previous studies have shown fixed-dose 4PCC to be as effective as standard-dose 4PCC for warfarin reversal. However, certain patient populations such as those with high total body weight (TBW) or elevated baseline INR may be at increased risk for treatment failure. The purpose of this study was to validate the efficacy of a novel fixed-dose 4PCC protocol for warfarin reversal. Methods This was a multi-centered observational comparison of patients who received 4PCC for warfarin reversal. Fixed-dose patients received 1500 units of 4PCC with the dose increased to 2000 units in patients with a baseline INR ≥ 7.5, a TBW ≥ 100 kg, or for intracranial hemorrhage (ICH). Standard-dosing followed manufacturer recommendations. The primary outcome was achievement of a post-4PCC INR of ≤1.4. Secondary outcomes included target INR achievement among patients with a baseline INR ≥ 7.5, a TBW ≥ 100 kg, or neurologic bleeding indications; hospital length of stay; cost of therapy; and thromboembolic complications. Results A total of 116 patients were included in the standard-dose group and 75 in the fixed-dose group. There was no difference in the primary outcome (65% vs 57%, p = 0.32). There was no difference in secondary outcomes aside from cost of therapy in which fixed-dose 4PCC was less expensive than standard-dose 4PCC. Conclusion A fixed-dose 4PCC regimen for warfarin reversal of 1500 units, with an increased dose of 2000 units for select patients, is as effective as standard-dose 4PCC for INR reversal.

Significance Many brain regions, notably the hippocampus, contain a record of the recent past with time cells, neurons that fire in sequence, each at a specific time after a triggering event. The origin of this neural timeline has been unclear. This paper reports a timing signal in the entorhinal cortex (EC), which provides input to the hippocampus. Rather than firing sequentially, all EC neurons activated shortly after a stimulus and then decayed at a variety of rates. Because different neurons decay at different rates, one can reconstruct how far in the past the stimulus was presented by noting which neurons are still active. These results align well with the theoretical proposal that the brain represents the real Laplace transform of the past., Episodic memory is believed to be intimately related to our experience of the passage of time. Indeed, neurons in the hippocampus and other brain regions critical to episodic memory code for the passage of time at a range of timescales. The origin of this temporal signal, however, remains unclear. Here, we examined temporal responses in the entorhinal cortex of macaque monkeys as they viewed complex images. Many neurons in the entorhinal cortex were responsive to image onset, showing large deviations from baseline firing shortly after image onset but relaxing back to baseline at different rates. This range of relaxation rates allowed for the time since image onset to be decoded on the scale of seconds. Further, these neurons carried information about image content, suggesting that neurons in the entorhinal cortex carry information about not only when an event took place but also, the identity of that event. Taken together, these findings suggest that the primate entorhinal cortex uses a spectrum of time constants to construct a temporal record of the past in support of episodic memory.

The tenets of neurosurgery worldwide, whether in the civilian or military sector, espouse vigilance, the ability to adapt, extreme ownership, and, of course, an innate drive for developing a unique set of technical skills. At a time in history when the complexity of battlefield neurotrauma climaxed coupled with a chronic shortage of military neurosurgeons, modernized solutions were mandated in order to deliver world-class neurological care to our servicemen and servicewomen. Complex blast injuries, as caused by an increased incidence of improvised explosive devices, yielded widespread systemic inflammatory responses with multiorgan damage. In response to these challenges, the "NeuroTeam," originally a unit of two neurosurgeons as deployed during Operation Desert Storm, was redesigned to instead pair a neurosurgeon with a neurointensivist and launched itself during two specialized missions in Operations Iraqi Freedom and Enduring Freedom. Representing a hybridized version of present-day neurocritical care teams, the purpose of this unit was to optimize neurosurgical care by focusing on interdisciplinary collaboration in an Echelon III combat support hospital. The NeuroTeam provided unique workflow capabilities never seen collectively on the battlefield: downrange neurosurgical capability by a board-certified neurological surgeon within 60 minutes from the point of injury paired with a neurocritical care–trained intensivist. This also set the stage for intraoperative telemedicine infrastructure for neurosurgery and optimized the ability to evaluate, triage, and stabilize patients prior to medical evacuation. This novel military partnership ultimately allowed the neurosurgeon to focus on the tenets of the craft and thereby the dynamic needs of the patient first and foremost. Since the success of these missions, the NeuroTeam has evolved into a detachable unit, the "Head and Neck Team," comprising neurosurgeons, otolaryngologists, and ophthalmologists, supported by a postinjury hospital unit, which includes an embedded neurocritical care physician. The creation and evolution of the NeuroTeam, necessitated by a shortage of military neurosurgeons and the dangerous shift in military wartime tactics, best exemplifies multidisciplinary collaboration and military medicine agility. As neurocritical care continues to evolve into a highly complex, distinct specialty, the lessons learned by the NeuroTeam ultimately serve as a reminder for civilian and military physicians alike. Despite the conditions and despite one’s professional ego, patients with highly complex morbid neurological disease deserve expert, multidisciplinary management for survival.

(s): Existing bladder-specific measures lack ability to assess a range of bladder health from poor to optimal health. We report evidence for validity of the self-administered, multidimensional Bladder Health Scales and Function Indices for research in adult women.A cross-sectional population-based validation study with random assignment to paper or electronic administration was conducted using national address-based probability sampling supplemented by purposive sampling of women with lower urinary tract symptoms surrounding 7 clinical research centers. Construct validity of the Bladder Health Scales and Function Indices was guided by Multitrait-Multimethod approach using health and condition-specific questionnaires, bladder diaries, expert ratings of bladder health, and noninvasive bladder function testing. Internal dimensional validity was evaluated using factor analysis; internal reliability was assessed using paired t-tests and 2-way mixed effects Intraclass Correlation Coefficient models. Mode comparisons used chi-square, Fisher Exact or t-tests. Convergent validity was evaluated using Pearson correlations with the external construct measures and known-group validity was established with comparison of women known and unknown to be symptomatic with urinary conditions.The sample included 1,072 participants. Factor analysis identified ten scales with Cronbach's alpha ranging 0.74-0.94. Intraclass correlation coefficients of scales ranged from 0.55-0.94. Convergent validity of ten scales and six indices ranged from 0.52- 0.83. Known-group validity was confirmed for all scales and indices. Item distribution was similar by mode of administration.The paper and electronic forms of the Bladder Health Scales and Function Indices are reliable and valid measures of bladder health for use in women's health research.

This article contributes to the understudied histories of scientific racism and cultural pluralism in Canada by exploring the early life and thought of Watson Kirkconnell. Kirkconnell, a university...

To estimate whether nitrofurantoin prophylaxis decreases the incidence of culture-documented urinary tract infection for women with catheter-managed urinary retention after pelvic reconstructive surgery.This double-blind, placebo-controlled, randomized trial was conducted at five academic institutions. Women with urinary retention after surgery for prolapse or incontinence were randomized to oral nitrofurantoin 100 mg daily during indwelling or clean intermittent self-catheterization. The primary outcome was the incidence of symptomatic urinary tract infection within 6 weeks of surgery, confirmed by culture demonstrating more than 1,000 colony forming units per milliliter of uropathogenic bacteria. Secondary outcomes were adverse symptoms possibly attributable to nitrofurantoin and bacterial resistance to nitrofurantoin. A sample size of 154 would detect a decrease in urinary tract infection incidence from 33% to 13%, with 80% power, two-sided alpha of 0.05, and allow 10% dropout.Of 154 participants randomized from September 2016 to May 2018, 151 were eligible for analysis: 75 received nitrofurantoin, and 76 received placebo. Demographics were similar between groups. The indication for surgery was prolapse (46%), incontinence (20%), or a combination (34%). Participants were discharged with an indwelling catheter (58%) or performing self-catheterization (42%). Median duration of catheter use was 4 days (interquartile range 3-7). Thirteen women in the nitrofurantoin group and 13 women in the placebo group experienced urinary tract infection (17.3% vs 17.1%, P=.97, relative risk [RR] [95% CI] 1.01 [0.50-2.04]). Adverse symptoms possibly attributable to nitrofurantoin were common in both groups (68% vs 61%, P=.34, RR [95% CI] 1.12 [0.88-1.43]). Resistance to nitrofurantoin was identified in seven urine cultures, four among nitrofurantoin and three among placebo recipients. In total, 52 urine cultures were obtained to evaluate symptoms of urinary tract infection, and only 27 of 52 grew at least 1,000 cfu/mL of uropathogenic bacteria.Daily nitrofurantoin did not reduce the incidence of culture-proven urinary tract infection among women with catheter-managed urinary retention after pelvic reconstructive surgery. Culture confirmed urinary tract infection in only half of symptomatic episodes.ClinicalTrials.gov, NCT02727322.

Obwohl Menschen mit einem Down-Syndrom (DS) aufgrund einer Triplikation des APP-Gens einem extrem hohen Risiko fur die Entwicklung einer Alzheimer-Demenz ausgesetzt sind, existieren kaum international gebrauchliche Testverfahren zur Erfassung kognitiver Defizite dieser Risikopopulation in deutscher Sprache. Ziele waren die Ubersetzung und interkulturelle Adaptation der im englischen und spanischen Sprachraum gebrauchlichen Cambridge Examination for Mental Disorders of Older People with Down’s Syndrome and Others with Intellectual Disabilities (CAMDEX-DS). Dieses Instrument zur Diagnostik und Verlaufsbeobachtung besteht aus einer testpsychologischen Untersuchung (CAMCOG-DS) und einem Betreuerinterview. Die Ubersetzung und Adaptation der CAMDEX-DS erfolgten in einem mehrstufigen Verfahren, wobei nach Anfertigung unabhangiger Hin- und Ruckubersetzungen jeweils Konsensusfassungen angefertigt und erprobt wurden. Die Endfassung des Betreuerinterviews wurde an 11 Probanden angewandt, die der CAMCOG-DS an 28. Die deutsche Fassung der CAMDEX-DS erwies sich als problemlos anwendbar. Die CAMCOG-DS konnte von 75 % der Patienten (21/28) in ihrer Ganze bearbeitet werden. Patienten ab dem 45. Lebensjahr zeigten deutlich niedrigere Gesamtpunktwerte als jungere Patienten (46/109 vs. 73,5/109; p = 0,033). Mit der CAMDEX-DS steht fur Menschen mit DS ein international anerkanntes Werkzeug zu Diagnostik und Verlaufsbeurteilung kognitiver Defizite zur Verfugung. Durch die deutsche Fassung kann die medizinische Versorgung dieser Patienten vereinheitlicht werden. Insbesondere erlaubt sie den Patienten im Sinne der Inklusion erstmals die Partizipation an internationalen Forschungsvorhaben.

The Traffic Injury Research Foundation (TIRF) developed and evaluated a new road test, called the Enhanced Road Test (ERT), to assess a driver’s cognitive fitness to drive for the Ministry of Transportation in Ontario, Canada (MTO). The ERT was designed to flag individuals for potential cognitive impairment, but was not meant to indicate, or assess the level of impairment. Practical feasibility for implementation of the ERT was determined in a pilot study as well as its ability to differentiate drivers with and without cognitive impairment. The research design included both process and outcome evaluation components. The qualitative process evaluation was conducted using surveys administered to participant drivers (N = 70) and feedback obtained from driver examiners involved in the pilot (N = 3). The quantitative outcome evaluation used an experimental design to administer the ERT to a sample of drivers with (N = 42), and without (N = 28), mild cognitive impairment. Regression analysis was conducted and scoring functions of the ERT were compared through a Receiver Operating Characteristic (ROC) curve analysis. Survey results revealed that drivers did not raise specific concerns about the ERT and that examiners believed more training on driving behaviours associated with cognitive impairment and some scoresheet formatting changes would be beneficial. ROC Area Under the Curve (AUC) results revealed that some components of the ERT were better at identifying individuals whose driving skills declined. These components are the adjust-control, route finding and divided attention tasks. Two final scoring schemes for the ERT are proposed as well as several recommendations for its possible implementation.

Atg8 family proteins are highly-conserved eukaryotic proteins with diverse autophagy and non-autophagic functions in eukaryotes. While the structural features required for conserved autophagy functions of Atg8 are well-established, little is known about the molecular changes that facilitated acquisition of divergent, non-autophagic functions of Atg8. The malaria parasite Plasmodium falciparum offers a unique opportunity to study non-autophagic functions of Atg8 family proteins because it encodes a single Atg8 homolog whose only essential function is in the inheritance of an unusual secondary plastid called the apicoplast. Here we used functional complementation to investigate the structure-function relationship for this divergent Atg8 protein. We showed that the LC3-interacting region (LIR) docking site (LDS), the major interaction interface of Atg8 protein family, is not sufficient for PfAtg8 apicoplast function. Other regions previously implicated in canonical Atg8 interactions, the ubiquitin-interacting motif (UIM) docking site (UDS) and the N-terminal helix are not required for PfAtg8 function. Finally, the unique Apicomplexan-specific loop previously implicated in interaction with membrane conjugation machinery in vitro, is not required in vivo neither for membrane conjugation nor for the effector function of PfAtg8. These results suggest that the effector function of PfAtg8 is mediated by structural features distinct from those previously identified for macroautophagy and selective autophagy functions.ImportanceThe most extensively studied role of Atg8 proteins is in autophagy. However, it is clear that they have other non-autophagic functions critical to cell function and disease pathogenesis yet understudied compared to their canonical role in autophagy. Mammalian cells contain multiple Atg8 paralogs that have diverse, specialized functions. Gaining molecular insight into their non-autophagic functions is difficult because of redundancy between the homologs and their role in both autophagy and non-autophagic pathways. Malaria parasites such as Plasmodium falciparum are a unique system to study a novel, non-autophagic function of Atg8 separate from its role in autophagy: They have only one Atg8 protein whose only essential function is in the inheritance of the apicoplast, a unique secondary plastid organelle. Insights into the molecular basis of PfAtg8’s function in apicoplast biogenesis will have important implications for the evolution of diverse non-autophagic functions of the Atg8 protein family.

BACKGROUND: Urgency and frequency are common lower urinary tract symptoms (UF-LUTS) in women. There is limited evidence to guide physical therapist-led treatment. OBJECTIVES: To compare hip and pelvic floor muscle strength between women with and without UF-LUTS. We hypothesized women with UF-LUTS would demonstrate 1) diminished hip external rotator and abductor strength and 2) equivalent pelvic floor strength and diminished endurance compared to controls. STUDY DESIGN: A matched case-control study METHODS: Women with UF-LUTS (cases) and controls were matched on age, body mass index (BMI), vaginal parity. Examiner measured participants’ 1) hip external rotator and abductor strength via dynamometry (maximum voluntary effort against fixed resistance) and 2) pelvic floor muscle strength (peak squeeze pressure) and endurance (squeeze pressure over a 10 second hold) via vaginal manometry. Values compared between cases and controls with paired-sample t-tests (hip) or Wilcoxon signed rank tests (pelvic floor). RESULTS: 21 pairs (42 women): Hip external rotation (67.0 ± 19.0 N vs 83.6 ± 21.5 N; P=0.005) and hip abduction strength (163.1 ± 48.1 N vs 190.1 ± 53.1 N; P=0.04) were significantly lower in cases than controls. There was no significant difference in pelvic floor strength (36.8 ± 19.9 cmH(2)0 vs 41.8 ± 21.0 cmH(2)0; P=0.40) or endurance (234.0 ± 149.6 cmH(2)0*seconds vs 273.4 ± 149.1 cmH(2)0*seconds; P=0.24). CONCLUSION: Women with UF-LUTS had weaker hip external rotator and abductor muscles, but similar pelvic floor strength and endurance compared to controls. Hip strength may be important to assess in patients with UF-LUTS, further research is needed.

Background Death, acute heart failure (AHF) and perioperative myocardial infarction/injury (PMI) are the most relevant cardiovascular complications following non-cardiac surgery. Unfortunately, the incidence of these complications are higher than expected. Currently available tools to predict these complications have only modest accuracy. Purpose To determine the accuracy of preoperative high-sensitivity cardiac troponin T (hs-cTnT) concentrations for prediction of mortality, AHF and PMI after non-cardiac surgery. Methods We prospectively included 4,709 patients at high cardiovascular risk undergoing non-cardiac surgery. Hs-cTnT concentrations were measured before surgery and, daily after surgery, for two days. PMI was defined as an absolute increase of 14ng/L (the 99th percentile of the assay used) from hs-cTnT baseline values. The primary endpoint was the diagnostic accuracy of preoperative hs-cTnT concentration to predict death, AHF and PMI within 30 days, as quantified by the area under the receiving-operating curve (AUC). Multivariate logistic regression analysis was performed to test the association between preoperative hs-cTnT and each endpoint. Results All-cause mortality occurred in 133 (3%), AHF in 84 (2%) and PMI in 742 (16%) patients. Preoperative hs-cTnT concentrations had good accuracy for prediction of death, AHF and PMI (AUC = 0.75 [95% CI, 0.71–0.79], 0.72 [95% CI, 0.67–0.77] and 0.73 [95% CI, 0.71–0.75], respectively). After adjusting for confounders, hs-cTnT remained an independent predictor for death with an adjusted odds ratio (aOR) of 2.1 (95% CI, 1.7–2.7, P Conclusion The preoperative hs-cTnT concentration has a good accuracy to predict mortality, AHF and PMI after non-cardiac surgery, but is an independent predictor only for mortality and PMI. A cut-off value of 5ng/L identifies a subgroup of patients at low risk for these complications. Funding Acknowledgement Type of funding source: Foundation. Main funding source(s): Swiss National Foundation, Swiss Herat Foundation

Plasmodium parasites, which cause malaria, and related apicomplexans are important human and veterinary pathogens. These parasites represent a highly divergent and understudied branch of eukaryotes, and as such often defy the expectations set by model organisms. One striking example of unique apicomplexan biology is the apicoplast, an essential but nonphotosynthetic plastid derived from an unusual secondary (eukaryote-eukaryote) endosymbiosis. Endosymbioses are a major driver of cellular innovation, and apicoplast biogenesis pathways represent a hot spot for molecular evolution. We previously conducted an unbiased screen for apicoplast biogenesis genes in P. falciparum to uncover these essential and innovative pathways. Here, we validate a novel gene candidate from our screen and show that its role in apicoplast biogenesis does not match its functional annotation predicted by model eukaryotes. Our findings suggest that an uncharacterized chloroplast maintenance pathway has been reused for complex plastid biogenesis in this divergent branch of pathogens., Plasmodium parasites and related apicomplexans contain an essential “complex plastid” organelle of secondary endosymbiotic origin, the apicoplast. Biogenesis of this complex plastid poses a unique challenge requiring evolution of new cellular machinery. We previously conducted a mutagenesis screen for essential apicoplast biogenesis genes to discover organellar pathways with evolutionary and biomedical significance. Here we validate and characterize a gene candidate from our screen, Pf3D7_0913500. Using a conditional knockdown strain, we show that Pf3D7_0913500 depletion causes growth inhibition that is rescued by the sole essential product of the apicoplast, isopentenyl pyrophosphate (IPP), and results in apicoplast loss. Because Pf3D7_0913500 had no previous functional annotation, we name it apicoplast-minus IPP-rescued 4 (AMR4). AMR4 has an annotated CaaX protease and bacteriocin processing (CPBP) domain, which in eukaryotes typically indicates a role in CaaX postprenylation processing. Indeed, AMR4 is the only putative CaaX-like protease in Plasmodium parasites which are known to require protein prenylation, and we confirm that the conserved catalytic residue of AMR4 (E352) is required for its apicoplast function. However, we unexpectedly find that AMR4 does not act in a CaaX postprenylation processing pathway in Plasmodium falciparum. Instead, we find that AMR4 is imported into the apicoplast and is derived from a cyanobacterial CPBP gene which was retained through both primary and secondary endosymbiosis. Our findings suggest that AMR4 is not a true CaaX protease, but instead it performs a conserved, uncharacterized chloroplast function that has been retained for complex plastid biogenesis.

We present estimates of common actions associated with under-ice surveys and their energetic costs by examining data collected by two versions of the tethered, battery-operated unmanned underwater vehicle Icefin during 175 hours of operations under sea ice, glaciers and ice shelves. Our method and analysis yield design guidance for battery-operated unmanned underwater vehicles (UUVs) based on empirical evidence of the energy used to conduct a variety of oceanographic surveys under ice. Operator decisions are shown to significantly change the variance of a common action, allowing for energy reduction by modifying operator behavior, preventing a costly design change. The total energy released while performing common under-ice survey actions are shown to illustrate the most significant opportunities for improved efficiency in future vehicle designs.

This paper describes the theoretical background, design, and fabrication efforts towards a sub-millimeter-scale polar-specific conductivity cell for use at the ice-ocean interfaces. Five different geometries for the conductivity cell for have been conceptualized and modeled. All five designs show potential to fulfill the design requirements. Fabrication efforts on the preferred design have been undertaken using traditional silicon-based processes. Challenges in the fabrication processes are addressed, with potential solutions discussed.

Sampling systems on small underwater vehicles are needed to enable important aspects of ocean and polar science and represent a compelling design challenge. We describe the design of a system for in situ ice and sediment sampling aboard the Icefin vehicle. Small robotic riverbed sediment samplers designed to minimize the ballast weight by using novel methods of generating coring forces show that lightweight underwater vehicles can successfully collect solid samples, but their form factors make them ill-suited to be deployed in polar environments. We explore the design and development of a functional prototype of a manipulator arm with a sediment sampling end effector, investigate the design improvements required for the system to be deployed as a part of Icefin's payload using both tests from the prototype as well as simulations of expected dynamics, and provide recommendations for adjusting the system for ice coring. We find that a prototype of the system is able to penetrate test sediment up to 1.5 inches and verifies the model of the system that is used to iterate upon the design.

Here we present the design of a custom water sampling system for use on the underwater robot Icefin. The goals of this instrument are to collect discrete water samples in a compact form factor, operate in extreme underwater environments including high pressure and low temperature settings, and maintain a simple low-cost design. To achieve these objectives the system integrates a fluidic manifold, several compact solenoid pumps and valves, electronic controls, and an oil filled housing. A first-generation version of the water sampler was successfully tested on the underwater robot Icefin during ocean deployments in McMurdo Sound, Antarctica. A second-generation version of the system with a 3D printed manifold and improved capabilities has since been developed and undergone preliminary lab tests.

Icefin is a custom designed remotely or autonomously operated vehicle (ROV/AUV) for sub-ice deployments in polar environments with a primary focus on modularity for deploying multiple payloads throughout a season to characterize the under-ice environment. Over the past six years the vehicle has undergone numerous design improvements to become a stable and robust platform. The current primary vehicle design was proven during the 2018 field campaign. With the success of that season, a second vehicle was built to accommodate two field campaigns in austral summer 2019–2020, wherein the vehicle dual Icefin vehicles were deployed through ~600m hot water drilled boreholes to investigate the grounding zones of Thwaites Glacier and the Ross Ice Shelf. Presented here is an overview of the engineering design updates that were incorporated from the 2017 season. Also presented are results and lessons learned from the 2019 deployments.

Forward-looking sonar is one of the most common and powerful instruments available for use in imaging underwater environments. Here, we explore the utility of these sonar sensors for mosaicking, mapping and topography reconstruction of areas of interest in our target under-ice and underwater environments. This is a difficult problem due to the noise in the sonar images as well as the changing appearance of objects when views from different points. Here we address the problem of sonar image alignment through sensor fusion with navigation instruments to provide an initial relative placement between sonar frames. We also discuss the use of such forward looking sonar sensors to build 3D point clouds of the ice topography.

Summary Background Lower urinary tract symptoms (LUTS) are common in children and adolescents. Non-invasive tests evaluating bladder function are generally preferred over invasive tests, yet few studies have explored the range of normative values for these tests in healthy, asymptomatic children. Objective To define normative reference ranges for non-invasive tests of bladder function in healthy, asymptomatic girls and adolescents. Study design A comprehensive search strategy was performed in seven electronic databases through October 2019. English-language studies reporting data on voiding frequency, voided and postvoid residual volumes (PVR) and uroflowmetry results in healthy, asymptomatic girls (mean age ≥ 5 years) were included. Two independent reviewers performed study review, data extraction, and quality assessment. Overall mean estimates and 95% confidence intervals for each bladder function parameter were calculated using random effects models, and 95% normative reference values were estimated. Results Ten studies met eligibility criteria for the meta-analysis (n = 2143 girls, age range: 3–18). Mean estimates of maximum voided volume and PVR were 233.4 ml (95% CI 204.3–262.6; n = 1 study) and 8.6 ml (95% CI 4.8–12.4; n = 2 studies) respectively. Pooled mean estimates for uroflowmetry parameters were: 21.5 ml/s (95% CI 20.5–2.5) for maximum flow rate (n = 6 studies), 12.5 ml/s (95% CI 11.2–13.8) for mean flow rate (n = 6 studies), 6.8 s (95% CI 4.4–9.3) for time to maximum flow (n = 3 studies), 15.7 s (95% CI 13.0–18.5) for flow time (n = 3 studies), and 198.7 ml (95% CI 154.2–234.2) for voided volume (n = 9 studies). No studies reported estimates of voiding frequency. Between-study heterogeneity was high (89.0–99.6%). Conclusions Although we were able to calculate pooled mean estimates for several parameters, the small number of included studies and the wide age ranges of participants preclude generalization of reference values to all healthy girls. Further research is needed to determine normative reference values within specific age groups.

Objective: This study examines student suggestions for other students, campuses, and society to address heavy episodic drinking (HED) and associated harms. Participants: Included 110 post-secondary...

Objectives The aims of the study were to systematically review the literature and to synthesize the evidence for the effectiveness of botulinum toxin injection to the pelvic floor muscles for treating pelvic floor myofascial pain in female patients. Methods This systematic literature search was performed in February 2018 and updated in September 2019. Articles were screened based on predefined criteria: (1) adult population, (2) female patients, (3) treatment of pelvic pain by transvaginal botulinum toxin injection into the pelvic floor, (4) published in English or English translation available, (5) study design including randomized controlled trials, cohort studies, and case series with more than 10 participants, and (6) quantitative report of pain scores. Nine studies were included in the primary analysis, and an unpublished study was included in a sensitivity analysis. A random effects model with robust variance estimation was used to estimate the pooled mean difference in patient-reported pain scores after botulinum toxin injection. Results A statistically significant reduction in patient-reported pain scores was noted at 6 weeks after botulinum toxin injection (mean difference, 20.3; 95% confidence interval, 11.7-28.9) and continued past 12 weeks (mean difference, 19.4; 95% confidence interval, 14.6-24.2). Significant improvement was noted in secondary outcomes including dyspareunia, dyschezia, and quality of life. Conclusions This systematic review and meta-analysis support the conduct of future, large-scale randomized controlled trials to determine the efficacy and optimize administration of botulinum toxin injections for treatment of pelvic floor myofascial pain and associated symptoms in women.

Icefin performed the first long range robotic exploration of the grounding zone of Thwaites Glacier from January 9-12 2020. Icefin was part of the MELT project of the International Thwaites Glacier Collaboration deployed to the grounding zone of Thwaites Glacier, West Antarctica over the period December 2019-February 2020. MELT is an interdisciplinary project to explore rapid change across the grounding zone, and in particular basal melting. The subglacial cavity ~2km north of the grounding zone was accessed via hot water drilling on January 7-8, 2020. Icefin, a hybrid autonomous and remotely operated underwater vehicle designed for sub-ice and borehole operations, conducted over 15km of round-trip data collection under the ice along a section of the glacier from the grounding zone extending to a point 4 km oceanward. The vehicle collected data with ten different science sensors including cameras, sonars, conductivity/temperature and dissolved oxygen. Overall, the water column ranged from ~100m downstream that narrowed quickly to an average of 50m that spanned over 2km, to a long segment of ~30m thickness before quickly narrowing over 500m towards the grounding zone. The seafloor structures run roughly parallel to ice flow direction, consisting of furrows, ridges, and grooves in some cases mirrored by the ice structure. The Icefin dives revealed a diverse set of basal ice conditions, with complex geometry, including a range of terraced features, smooth ablated surfaces, crevassing, sediment rich layers of varying kinds, as well as interspersed clear, potentially accreted freshwater ice. The ocean directly beneath the ice varies spatially, from moderately well-mixed near the grounding zone to highly stratified within and below concavities in the ice downstream. Sediments along the sea floor range from fine grained downstream to course angular gravel near the grounding zone distributed between larger boulders. We observed rocky material in the ice that ranged from fine grained layers compressed within the ice to small angular particles volumetrically distributed within ice, to gravel and cobbles, as well as trapped boulders up to meter scale. In addition to the oceanographic, glaciological and sea floor conditions, we also catalogued communities of organisms along the seafloor and ice-ocean interface. We will report the highlights and initial conclusions from Icefin’s in situ data collection, and offer perspectives on change at the grounding zone.

Obstetric anal sphincter injuries (OASISs) complicate up to 11% of vaginal deliveries; obstetricians must be able to recognize and manage these technically challenging injuries.The aim of this study was to share our approach for management of these challenging complications of childbirth based on a multidisciplinary collaboration between general obstetrician-gynecologists, maternal fetal medicine specialists, and female pelvic medicine and reconstructive surgeons established at our institution.A systematic literature search was performed in 3 search engines: PubMed 1946-, EMBASE 1947-, and the Cochrane Database of Systematic Reviews using keywordsIdentification should begin with an assessment of risk factors, notably nulliparity and operative vaginal delivery, consistently associated with the highest risk of OASISs, and proceed with a thorough examination to grade the degree of laceration. Repair should be performed or supervised by an experienced clinician in an operating room with either regional or general anesthesia. The external anal sphincter may be repaired using either an overlapping or end-to-end anastomosis. Providers should be comfortable with both approaches as the degree of laceration may necessitate one approach over the other. We advocate for use of monofilament suture on all layers to decrease risk of bacterial seeding, as well as preoperative antibiotics and postoperative bowel regimen, which are associated with improved outcomes.Long-term sequelae, including pain, dyspareunia, and fecal incontinence, significantly impact quality of life for many patients who suffer OASISs and may be avoided if evidence-based guidelines for recognition and repair are utilized.