Bayesian optimisation of hexagonal honeycomb metamaterial

Periodic mechanical metamaterials, such as hexagonal honeycombs, have traditionally been designed with uniform cell walls to simplify manufacturing and modelling. However, recent research has suggested that varying strut thickness within the lattice could improve its mechanical properties. To fully explore this design space, we developed a computational framework that leverages Bayesian optimisation to identify configurations with increased uniaxial effective elastic stiffness and plastic or buckling strength. The best topologies found, representative of relative densities with distinct failure modes, were additively manufactured and tested, resulting in a 54% increase in stiffness without compromising the buckling strength for slender architectures, and a 63% increase in elastic modulus and a 88% increase in plastic strength for higher volume fractions. Our results demonstrate the potential of Bayesian optimisation and solid material redistribution to enhance the performance of mechanical metamaterials

b-Initiated processes at the LHC: a reappraisal

Several key processes at the LHC in the standard model and beyond that involve $b$ quarks, such as single-top, Higgs, and weak vector boson associated production, can be described in QCD either in a 4-flavor or 5-flavor scheme. In the former, $b$ quarks appear only in the final state and are typically considered massive. In 5-flavor schemes, calculations include $b$ quarks in the initial state, are simpler and allow the resummation of possibly large initial state logarithms of the type $\log \frac{{\cal Q}^2}{m_b^2}$ into the $b$ parton distribution function (PDF), ${\cal Q}$ being the typical scale of the hard process. In this work we critically reconsider the rationale for using 5-flavor improved schemes at the LHC. Our motivation stems from the observation that the effects of initial state logs are rarely very large in hadron collisions: 4-flavor computations are pertubatively well behaved and a substantial agreement between predictions in the two schemes is found. We identify two distinct reasons that explain this behaviour, i.e., the resummation of the initial state logarithms into the $b$-PDF is relevant only at large Bjorken $x$ and the possibly large ratios ${\cal Q}^2/m_b^2$'s are always accompanied by universal phase space suppression factors. Our study paves the way to using both schemes for the same process so to exploit their complementary advantages for different observables, such as employing a 5-flavor scheme to accurately predict the total cross section at NNLO and the corresponding 4-flavor computation at NLO for fully exclusive studies.Comment: Fixed typo in Eq. (A.10) and few typos in Eq. (C.2) and (C.3

Meropenem vs standard of care for treatment of neonatal late onset sepsis (NeoMero1): A randomised controlled trial.

BACKGROUND: The early use of broad-spectrum antibiotics remains the cornerstone for the treatment of neonatal late onset sepsis (LOS). However, which antibiotics should be used is still debatable, as relevant studies were conducted more than 20 years ago, recruited in single centres or countries, evaluated antibiotics not in clinical use anymore and had variable inclusion/exclusion criteria and outcome measures. Moreover, antibiotic-resistant bacteria have become a major problem in many countries worldwide. We hypothesized that efficacy of meropenem as a broad-spectrum antibiotic is superior to standard of care regimens (SOC) in empiric treatment of LOS and aimed to compare meropenem to SOC in infants aged 44 weeks meeting the Goldstein criteria of sepsis, were randomized in a 1:1 ratio to receive meropenem or one of the two SOC regimens (ampicillin+gentamicin or cefotaxime+gentamicin) chosen by each site prior to the start of the study for 8-14 days. The primary outcome was treatment success (survival, no modification of allocated therapy, resolution/improvement of clinical and laboratory markers, no need of additional antibiotics and presumed/confirmed eradication of pathogens) at test-of-cure visit (TOC) in full analysis set. Stool samples were tested at baseline and Day 28 for meropenem-resistant Gram-negative organisms (CRGNO). The primary analysis was performed in all randomised patients and in patients with culture confirmed LOS. Proportions of participants with successful outcome were compared by using a logistic regression model adjusted for the stratification factors. From September 3, 2012 to November 30th 2014, total of 136 patients (instead of planned 275) in each arm were randomized; 140 (52%) were culture positive. Successful outcome at TOC was achieved in 44/136 (32%) in the meropenem arm vs. 31/135 (23%) in the SOC arm (p = 0.087). The respective numbers in patients with positive cultures were 17/63 (27%) vs. 10/77 (13%) (p = 0.022). The main reason of failure was modification of allocated therapy. Treatment emergent adverse events occurred in 72% and serious adverse events in 17% of patients, the Day 28 mortality was 6%. Cumulative acquisition of CRGNO by Day 28 occurred in 4% of patients in the meropenem and 12% in the SOC arm (p = 0.052). CONCLUSIONS: Within this study population, we found no evidence that meropenem was superior to SOC in terms of success at TOC, short term hearing disturbances, safety or mortality were similar in both treatment arms but the study was underpowered to detect the planned effect. Meropenem treatment did not select for colonization with CRGNOs. We suggest that meropenem as broad-spectrum antibiotic should be reserved for neonates who are more likely to have Gram-negative LOS, especially in NICUs where microorganisms producing extended spectrum- and AmpC type beta-lactamases are circulating

Health care restructuring and family physician care for those who died of cancer

BACKGROUND: During the 1990s, health care restructuring in Nova Scotia resulted in downsized hospitals, reduced inpatient length of stay, capped physician incomes and restricted practice locations. Concurrently, the provincial homecare program was redeveloped and out-of-hospital cancer deaths increased from 20% (1992) to 30% (1998). These factors all pointed to a transfer of end-of-life inpatient hospital care to more community-based care. The purpose of this study was to describe the trends in the provision of Family Physician (FP) visits to advanced cancer patients in Nova Scotia (NS) during the years of health care restructuring. METHODS: Design Secondary multivariate analysis of linked population-based datafiles including the Queen Elizabeth II Health Sciences Centre Oncology Patient Information System (NS Cancer Registry, Vital Statistics), the NS Hospital Admissions/Separations file and the Medical Services Insurance Physician Services database. Setting Nova Scotia, an eastern Canadian province (population: 950,000). Subjects: All patients who died of lung, colorectal, breast or prostate cancer between April 1992 and March 1998 (N = 7,212). Outcome Measures Inpatient and ambulatory FP visits, ambulatory visits by location (office, home, long-term care facility, emergency department), time of day (regular hours, after hours), total length of inpatient hospital stay and number of hospital admissions during the last six months of life. RESULTS: In total, 139,641 visits were provided by family physicians: 15% of visits in the office, 10% in the home, 5% in the emergency department (ED), 5% in a long-term-care centre and 64% to hospital inpatients. There was no change in the rate of FP visits received for office, home and long-term care despite the fact that there were 13% fewer hospital admissions, and length of hospital stay declined by 21%. Age-sex adjusted estimates using negative binomial regression indicate a decline in hospital inpatient FP visits over time compared to 1992–93 levels (for 1997–98, adjusted RR = 0.88, 95%CI = 0.81–0.95) and an increase in FP ED visits (for 1997–98, adjusted RR = 1.18, 95%CI = 1.05–1.34). CONCLUSION: Despite hospital downsizing and fewer deaths occurring in hospitals, FP ambulatory visits (except for ED visits) did not rise correspondingly. Although such restructuring resulted in more people dying out of hospital, it does not appear FPs responded by providing more medical care to them in the community

Synthetic Lethality of Chk1 Inhibition Combined with p53 and/or p21 Loss During a DNA Damage Response in Normal and Tumor Cells

Cell cycle checkpoints ensure genome integrity and are frequently compromised in human cancers. A therapeutic strategy being explored takes advantage of checkpoint defects in p53-deficient tumors in order to sensitize them to DNA-damaging agents by eliminating Chk1-mediated checkpoint responses. Using mouse models, we demonstrated that p21 is a key determinant of how cells respond to the combination of DNA damage and Chk1 inhibition (combination therapy) in normal cells as well as in tumors. Loss of p21 sensitized normal cells to the combination therapy much more than did p53 loss and the enhanced lethality was partially blocked by CDK inhibition. In addition, basal pools of p21 (p53 independent) provided p53 null cells with protection from the combination therapy. Our results uncover a novel p53-independent function for p21 in protecting cells from the lethal effects of DNA damage followed by Chk1 inhibition. As p21 levels are low in a significant fraction of colorectal tumors, they are predicted to be particularly sensitive to the combination therapy. Results reported in this study support this prediction

Awareness of warning signs among suburban Nigerians at high risk for stroke is poor: A cross-sectional study

<p>Abstract</p> <p>Background</p> <p>Although stroke is a leading cause of morbidity and mortality in Nigeria, there is no information on awareness of its warning signs. This study was designed to assess awareness of stroke warning signs in Nigerians at increased risk.</p> <p>Methods</p> <p>A hospital-based cross-sectional study conducted at Irrua Specialist Teaching Hospital, in southern Nigeria. Patients with a diagnosis of hypertension, diabetes or both were interviewed for the warning signs of stroke in the outpatient clinic by trained interviewers. The main outcome measure was ability to identify at least one stroke warning sign.</p> <p>Results</p> <p>There were 225 respondents with a mean age of 58.0 ± 11.7 years. Only 39.6% could identify at least one stroke warning sign while the commonest sign identified was sudden unilateral limb weakness (24.4%). On multivariate logistic regression analysis, male sex (β = 0.26, 95% CI = 0.14–0.39, p < 0.001) and 11 or more years of education (β = 0.16, 95% CI = 0.03–0.29, p = 0.02) emerged the independent predictors of ability to identify at least one warning sign.</p> <p>Conclusion</p> <p>Awareness of stroke warning signs is poor among Nigerians at increased risk for the disease. Efforts should be made to improve on the level of awareness through aggressive health education.</p