Improving DRAM Performance by Parallelizing Refreshes with Accesses

Modern DRAM cells are periodically refreshed to prevent data loss due to leakage. Commodity DDR DRAM refreshes cells at the rank level. This degrades performance significantly because it prevents an entire rank from serving memory requests while being refreshed. DRAM designed for mobile platforms, LPDDR DRAM, supports an enhanced mode, called per-bank refresh, that refreshes cells at the bank level. This enables a bank to be accessed while another in the same rank is being refreshed, alleviating part of the negative performance impact of refreshes. However, there are two shortcomings of per-bank refresh. First, the per-bank refresh scheduling scheme does not exploit the full potential of overlapping refreshes with accesses across banks because it restricts the banks to be refreshed in a sequential round-robin order. Second, accesses to a bank that is being refreshed have to wait. To mitigate the negative performance impact of DRAM refresh, we propose two complementary mechanisms, DARP (Dynamic Access Refresh Parallelization) and SARP (Subarray Access Refresh Parallelization). The goal is to address the drawbacks of per-bank refresh by building more efficient techniques to parallelize refreshes and accesses within DRAM. First, instead of issuing per-bank refreshes in a round-robin order, DARP issues per-bank refreshes to idle banks in an out-of-order manner. Furthermore, DARP schedules refreshes during intervals when a batch of writes are draining to DRAM. Second, SARP exploits the existence of mostly-independent subarrays within a bank. With minor modifications to DRAM organization, it allows a bank to serve memory accesses to an idle subarray while another subarray is being refreshed. Extensive evaluations show that our mechanisms improve system performance and energy efficiency compared to state-of-the-art refresh policies and the benefit increases as DRAM density increases.Comment: The original paper published in the International Symposium on High-Performance Computer Architecture (HPCA) contains an error. The arxiv version has an erratum that describes the error and the fix for i

Diagnosis, Treatment, and Outcomes in Children With Congenital Nephrogenic Diabetes Insipidus: A Pediatric Nephrology Research Consortium Study

© Copyright © 2020 D\u27Alessandri-Silva, Carpenter, Ayoob, Barcia, Chishti, Constantinescu, Dell, Goodwin, Hashmat, Iragorri, Kaspar, Mason, Misurac, Muff-Luett, Sethna, Shah, Weng, Greenbaum and Mahan. Background and Objectives: Congenital or primary nephrogenic diabetes insipidus (NDI) is a rare genetic disorder that severely impairs renal concentrating ability, resulting in massive polyuria. There is limited information about prognosis or evidence guiding the management of these patients, either in the high-risk period after diagnosis, or long-term. We describe the clinical presentation, genetic etiology, treatment and renal outcomes in a large group of children (89%) and white (67%). Median age at diagnosis was 4.2 months interquartile range (IQR 1.1, 9.8). A desmopressin acetate loading test was administered to 46% of children at a median age of 4.8 months (IQR 2.8, 7.6); only 15% had a water restriction test. Genetic testing or a known family history was present in 70% of the patients; out of those genetically tested, 89 and 11% had mutations in AVPR2 and AQP2, respectively. No positive family history or genetic testing was available for 30%. The most common treatments were thiazide diuretics (74%), potassium-sparing diuretics (67%) and non-steroidal anti-inflammatory drugs (42%). At the time of first treatment, 70 and 71% of children were below −2 standard deviations (SD) for weight and height, respectively. At last follow-up, median age was 72.3 months (IQR 40.9, 137.2) and the percentage below −2 SD improved to 29% and 38% for weight and height, respectively. Adverse outcomes included inpatient hospitalizations (61%), urologic complications (37%), and chronic kidney disease (CKD) stage 2 or higher in 23%. Conclusion: We found the majority of patients were treated with thiazides with either a potassium sparing diuretic and/or NSAIDs. Hospitalizations, urologic complications, short stature, and CKD were common. Prospective trials to evaluate different treatment strategies are needed to attempt to improve outcomes

Sodium/myo-Inositol Transporters: Substrate Transport Requirements and Regional Brain Expression in the TgCRND8 Mouse Model of Amyloid Pathology

Inositol stereoisomers, myo- and scyllo-inositol, are known to enter the brain and are significantly elevated following oral administration. Elevations in brain inositol levels occur across a concentration gradient as a result of active transport from the periphery. There are two sodium/myo-inositol transporters (SMIT1, SMIT2) that may be responsible for regulating brain inositol levels. The goals of this study were to determine the effects of aging and Alzheimer's disease (AD)-like amyloid pathology on transporter expression, to compare regional expression and to analyze substrate requirements of the inositol transporters. QPCR was used to examine expression of the two transporters in the cortex, hippocampus and cerebellum of TgCRND8 mice, a mouse model of amyloid pathology, in comparison to non-transgenic littermates. In addition, we examined the structural features of inositol required for active transport, utilizing a cell-based competitive uptake assay. Disease pathology did not alter transporter expression in the cortex or hippocampus (p>0.005), with only minimal effects of aging observed in the cerebellum (SMIT1: F2,26 = 12.62; p = 0.0002; SMIT2: F2,26 = 8.71; p = 0.0015). Overall, brain SMIT1 levels were higher than SMIT2, however, regional differences were observed. For SMIT1, at 4 and 6 months cerebellar SMIT1 levels were significantly higher than cortical and hippocampal levels (p<0.05). For SMIT2, at all three ages both cortical and cerebellar SMIT2 levels were significantly higher than hippocampal levels (p<0.05) and at 4 and 6 months of age, cerebellar SMIT2 levels were also significantly higher than cortical levels (p<0.05). Inositol transporter levels are stably expressed as a function of age, and expression is unaltered with disease pathology in the TgCRND8 mouse. Given the fact that scyllo-inositol is currently in clinical trials for the treatment of AD, the stable expression of inositol transporters regardless of disease pathology is an important finding

Utilisation of an operative difficulty grading scale for laparoscopic cholecystectomy

Background A reliable system for grading operative difficulty of laparoscopic cholecystectomy would standardise description of findings and reporting of outcomes. The aim of this study was to validate a difficulty grading system (Nassar scale), testing its applicability and consistency in two large prospective datasets. Methods Patient and disease-related variables and 30-day outcomes were identified in two prospective cholecystectomy databases: the multi-centre prospective cohort of 8820 patients from the recent CholeS Study and the single-surgeon series containing 4089 patients. Operative data and patient outcomes were correlated with Nassar operative difficultly scale, using Kendall’s tau for dichotomous variables, or Jonckheere–Terpstra tests for continuous variables. A ROC curve analysis was performed, to quantify the predictive accuracy of the scale for each outcome, with continuous outcomes dichotomised, prior to analysis. Results A higher operative difficulty grade was consistently associated with worse outcomes for the patients in both the reference and CholeS cohorts. The median length of stay increased from 0 to 4 days, and the 30-day complication rate from 7.6 to 24.4% as the difficulty grade increased from 1 to 4/5 (both p < 0.001). In the CholeS cohort, a higher difficulty grade was found to be most strongly associated with conversion to open and 30-day mortality (AUROC = 0.903, 0.822, respectively). On multivariable analysis, the Nassar operative difficultly scale was found to be a significant independent predictor of operative duration, conversion to open surgery, 30-day complications and 30-day reintervention (all p < 0.001). Conclusion We have shown that an operative difficulty scale can standardise the description of operative findings by multiple grades of surgeons to facilitate audit, training assessment and research. It provides a tool for reporting operative findings, disease severity and technical difficulty and can be utilised in future research to reliably compare outcomes according to case mix and intra-operative difficulty

Antibodies Targeted to the Brain with Image-Guided Focused Ultrasound Reduces Amyloid-β Plaque Load in the TgCRND8 Mouse Model of Alzheimer's Disease

Immunotherapy for Alzheimer's disease (AD) relies on antibodies directed against toxic amyloid-beta peptide (Aβ), which circulate in the bloodstream and remove Aβ from the brain [1], [2]. In mouse models of AD, the administration of anti-Aβ antibodies directly into the brain, in comparison to the bloodstream, was shown to be more efficient at reducing Aβ plaque pathology [3], [4]. Therefore, delivering anti-Aβ antibodies to the brain of AD patients may also improve treatment efficiency. Transcranial focused ultrasound (FUS) is known to transiently-enhance the permeability of the blood-brain barrier (BBB) [5], allowing intravenously administered therapeutics to enter the brain [6]–[8]. Our goal was to establish that anti-Aβ antibodies delivered to the brain using magnetic resonance imaging-guided FUS (MRIgFUS) [9] can reduce plaque pathology. To test this, TgCRND8 mice [10] received intravenous injections of MRI and FUS contrast agents, as well as anti-Aβ antibody, BAM-10. MRIgFUS was then applied transcranially. Within minutes, the MRI contrast agent entered the brain, and BAM-10 was later found bound to Aβ plaques in targeted cortical areas. Four days post-treatment, Aβ pathology was significantly reduced in TgCRND8 mice. In conclusion, this is the first report to demonstrate that MRIgFUS delivery of anti-Aβ antibodies provides the combined advantages of using a low dose of antibody and rapidly reducing plaque pathology

Fast-timing measurements in ⁹⁶Pd:improved accuracy for the lifetime of the 4⁺₁ state

Direct lifetime measurements via γ–γ coincidences using the FATIMA fast-timing LaBr3(Ce) array were performed for the excited states below previously reported isomers. In the N = 50 semi-magic 96Pd nucleus, lifetimes below the I π = 8+ seniority isomer were addressed as a benchmark for further analysis. The results for the I π = 2+ and 4 + states confirm the published values. Increased accuracy for the lifetime value was achieved for the 4 + state.peerReviewe

Status and perspectives of hospital mortality in a public urban Hellenic hospital, based on a five-year review

<p>Abstract</p> <p>Background</p> <p>Analysis of hospital mortality helps to assess the standards of health-care delivery.</p> <p>Methods</p> <p>This is a retrospective cohort study evaluating the causes of deaths which occurred during the years 1995–1999 in a single hospital. The causes of death were classified according to the International Statistical Classification of Diseases (ICD-10).</p> <p>Results</p> <p>Of the 149,896 patients who were discharged the 5836 (3.4%) died. Males constituted 55% and females 45%. The median age was 75.1 years (1 day – 100 years).</p> <p>The seven most common ICD-10 chapters IX, II, IV, XI, XX, X, XIV included 92% of the total 5836 deaths.</p> <p>The most common contributors of non-neoplasmatic causes of death were cerebrovascular diseases (I60–I69) at 15.8%, ischemic heart disease (I20–I25) at 10.3%, cardiac failure (I50.0–I50.9) at 7.9%, diseases of the digestive system (K00–K93) at 6.7%, diabetes mellitus (E10–E14) at 6.6%, external causes of morbidity and mortality (V01–Y98) at 6.2%, renal failure (N17–N19) at 4.5%, influenza and pneumonia (J10–J18) at 4.1% and certain infectious and parasitic diseases (A00–B99) at 3.2%, accounting for 65.3% of the total 5836 deaths.</p> <p>Neoplasms (C00–D48) caused 17.7% (n = 1027) of the total 5836 deaths, with leading forms being the malignant neoplasms of bronchus and lung (C34) at 3.5% and the malignant neoplasms of large intestine (C18–21.2) at 1.5%. The highest death rates occurred in the intensive care unit (23.3%), general medicine (10.7%), cardiology (6.5%) and nephrology (5.5%).</p> <p>Key problems related to certification of death were identified. Nearly half of the deaths (49.3%: n = 2879) occurred by the completion of the third day, which indicates the time limits for investigation and treatment. On the other hand, 6% (n = 356) died between the 29^thand 262^nddays after admission.</p> <p>Inadequacies of the emergency care service, infection control, medical oncology, rehabilitation, chronic and terminal care facilities, as well as lack of regional targets for reducing mortality related to diabetes, recruitment of organ donors, provision for the aging population and lack of prevention programs were substantiated.</p> <p>Conclusion</p> <p>Several important issues were raised. Disease specific characteristics, as well as functional and infrastructural inadequacies were identified and provided evidence for defining priorities and strategies for improving the standards of care. Effective transformation can promise better prospects.</p

Incidence and outcomes of neonatal acute kidney injury (AWAKEN): a multicentre, multinational, observational cohort study

Background: Single-center studies suggest that neonatal acute kidney injury (AKI) is associated with poor outcomes. However, inferences regarding the association between AKI, mortality, and hospital length of stay are limited due to the small sample size of those studies. In order to determine whether neonatal AKI is independently associated with increased mortality and longer hospital stay, we analyzed the Assessment of Worldwide Acute Kidney Epidemiology in Neonates (AWAKEN) database. Methods: All neonates admitted to 24 participating neonatal intensive care units from four countries (Australia, Canada, India, United States) between January 1 and March 31, 2014, were screened. Of 4273 neonates screened, 2022 (47·3%) met study criteria. Exclusion criteria included: no intravenous fluids ≥48 hours, admission ≥14 days of life, congenital heart disease requiring surgical repair at <7 days of life, lethal chromosomal anomaly, death within 48 hours, inability to determine AKI status or severe congenital kidney abnormalities. AKI was defined using a standardized definition -i.e., serum creatinine rise of ≥0.3 mg/dL (26.5 mcmol/L) or ≥50% from previous lowest value, and/or if urine output was <1 mL/kg/h on postnatal days 2 to 7. Findings: Incidence of AKI was 605/2022 (29·9%). Rates varied by gestational age groups (i.e., ≥22 to <29 weeks =47·9%; ≥29 to <36 weeks =18·3%; and ≥36 weeks =36·7%). Even after adjusting for multiple potential confounding factors, infants with AKI had higher mortality compared to those without AKI [(59/605 (9·7%) vs. 20/1417 (1·4%); p< 0.001; adjusted OR=4·6 (95% CI=2·5-8·3); p=<0·0001], and longer hospital stay [adjusted parameter estimate 8·8 days (95% CI=6·1-11·5); p<0·0001]. Interpretation: Neonatal AKI is a common and independent risk factor for mortality and longer hospital stay. These data suggest that neonates may be impacted by AKI in a manner similar to pediatric and adult patients