bluuebunny/crossref_metadata_2025 huggingface dataset:
Earth and Moon impact flux increased at the end of the Paleozoic
Authors: Mazrouei Sara , Ghent Rebecca R. , Bottke William F. , Parker Alex H. , Gernon Thomas M.
Published: January 2019

Impact rates on Earth and the Moon

The rate at which impacts produce craters on the Moon is used to calibrate ages in planetary science. Earth should also have received similar numbers of impacts, but many craters have been hidden by erosion, ice sheets, and so on. Mazrouei
et al.
used infrared images of the Moon to estimate the ages of young lunar craters (see the Perspective by Koeberl). They found that the impact rate increased within the past ∼500 million years, a conclusion strengthened by an analysis of known impact craters on Earth. Crater size distributions are the same on Earth and the Moon over this period, implying that terrestrial erosion affects all craters equally, regardless of their size.

Science
, this issue p.
253
; see also p.
224
The importance of synthetic chemistry in the pharmaceutical industry
Authors: Campos Kevin R. , Coleman Paul J. , Alvarez Juan C. , Dreher Spencer D. , Garbaccio Robert M. , Terrett Nicholas K. , Tillyer Richard D. , Truppo Matthew D. , Parmee Emma R.
Published: January 2019

Synthetic innovation in drug development

Chemical synthesis plays a key role in pharmaceutical research and development. Campos
et al.
review some of the advantages that have come from recent innovations in synthetic methods. In particular, they highlight small-molecule catalysts stimulated by visible light, enzymes engineered for versatility beyond their intrinsic function, and bio-orthogonal reactions to selectively modify proteins for conjugation. High-throughput techniques are also poised to accelerate methods optimization from small-scale discovery to large-scale production, and complementary machine-learning approaches are just coming into focus.

Science
, this issue p.
eaat0805
Observation of magnetically tunable Feshbach resonances in ultracold
23
Na
40
K +
40
K collisions
Authors: Yang Huan , Zhang De-Chao , Liu Lan , Liu Ya-Xiong , Nan Jue , Zhao Bo , Pan Jian-Wei
Published: January 2019

Brief get-togethers between NaK and K

Cooling molecules to nanokelvin temperatures places them under the tightest quantum mechanical constraints. Studies in this intriguing regime have been limited to diatomics: Two cold atoms can be lured together into weakly associated Feshbach resonances, which lasers can then shift into a more stable molecular state. Yang
et al.
now report the observation of triatomic Feshbach resonances in ultracold collisions between potassium (K) atoms and sodium potassium (NaK) diatomics. The findings potentially set the stage for the preparation and study of ultracold triatomic molecules.

Science
, this issue p.
261
Oversight of direct-to-consumer neurotechnologies
Authors: Wexler Anna , Reiner Peter B.
Published: January 2019

Efficacy of products is far from clear
Nuclear power and promise
Confessions of a Rogue Nuclear Regulator
Gregory B. Jaczko
Simon and Schuster, 2019. 207 pp.
Authors: Hamblin Jacob Darwin
Published: January 2019

Deference to industry trumps safety in the U.S., warns a controversial former regulator
Dalbavancin Alone and in Combination with Ceftaroline against Four Different Phenotypes of
Staphylococcus aureus
in a Simulated Pharmacodynamic/Pharmacokinetic Model
Authors: Kebriaei Razieh , Rice Seth A. , Stamper Kyle C. , Rybak Michael J.
Published: January 2019

Glycopeptides such as vancomycin have been used as the first-line therapy against MRSA infections for over half a century. Reduced susceptibility and emergence of resistance to first-generation glycopeptides has led to development of second-generation lipoglycopeptide derivatives such as dalbavancin which hold broader ranges of activity and enhanced pharmacokinetic properties.
Population Pharmacokinetic Analyses for Plazomicin Using Pooled Data from Phase 1, 2, and 3 Clinical Studies
Authors: Trang Michael , Seroogy Julie D. , Van Wart Scott A. , Bhavnani Sujata M. , Kim Aryun , Gibbons Jacqueline A. , Ambrose Paul G. , Rubino Christopher M.
Published: January 2019

Plazomicin is an aminoglycoside with activity against multidrug-resistant
Enterobacteriaceae
. Plazomicin is dosed on a milligram-per-kilogram-of-body-weight basis and administered by a 30-min intravenous infusion every 24 h, with dose adjustments being made for renal impairment and a body weight (BW) of ≥125% of ideal BW.
Invasive Nontyphoidal
Salmonella
Disease in Africa
Authors: Gilchrist James J. , MacLennan Calman A.
Published: January 2019

Nontyphoidal salmonellae (NTS) are a major cause of invasive (iNTS) disease in sub-Saharan Africa, manifesting as bacteremia and meningitis. Available epidemiological data indicate that iNTS disease is endemic in much of the region. Antimicrobial resistance is common and case fatality rates are high. There are well-characterized clinical associations with iNTS disease, including young age, HIV infection, malaria, malnutrition, anemia, and sickle cell disease. However, the clinical presentation of iNTS disease is often with fever alone, so clinical diagnosis is impossible without blood culture confirmation. No vaccine is currently available, making this a priority area for global health research. Over the past ten years, it has emerged that iNTS disease in Africa is caused by distinct pathovars of
Salmonella
Typhimurium, belonging to sequence type ST313, and
Salmonella
Enteritidis. These are characterized by genome degradation and appear to be adapting to an invasive lifestyle. Investigation of rare patients with primary immunodeficiencies has suggested a key role for interferon gamma–mediated immunity in host defense against NTS. This concept has been supported by recent population-based host genetic studies in African children. In contrast, immunoepidemiological studies from Africa indicate an important role for antibody for protective immunity, supporting the development of antibody-inducing vaccines against iNTS disease. With candidate O-antigen–based vaccines due to enter clinical trials in the near future, research efforts should focus on understanding the relative contributions of antibody and cell-mediated immunity to protection against iNTS disease in humans.
Rare presentation of iron deficiency anaemia with cerebral venous sinus thrombosis in a middle-aged woman
Authors: Bibi Amna , Liyanapthirana Chathuri , Khan Sajjad
Published: January 2019

This is a case of a female patient presented with a mild headache associated with recurrent episodes of nausea and vomiting, confusion and right-sided hemiparesis, diagnosed of haemorrhagic venous infarction from the thrombosis of left transverse and sigmoid sinus and probably the left vein of Labbe. She had severe microcytic hypochromic anaemia due to iron deficiency, without any other risk factors for cerebral venous thrombosis such as trauma history, infections, coagulation disorders or autoimmune diseases. She had a good prognosis after iron supplementation and anticoagulation therapy.
Solid papillary thyroid carcinoma with Hashimoto’s thyroiditis: description of a further case with challenging cytological features
Authors: Fulciniti Franco , Barizzi Jessica , Trimboli Pierpaolo , Giovanella Luca
Published: January 2019

Solid papillary thyroid carcinoma (SV-PTC) is a rare variant which is mainly observed in young patients with a history of exposure to ionising radiations. Neoplasms belonging to such category generally carry RET-PTC (REarranged during Transfection- Papillary Thyroid Carcinoma) fusions and seem to have a slightly worse prognosis with respect to classical and follicular variants of papillary thyroid carcinoma (PTC), though consistent prognostic and survival data are scarce. SV-PTC should be differentiated from trabecular-insular poorly differentiated thyroid carcinomas, which occur in a different age group and carry a dismal prognosis. These latter tumours do not show the typical nuclear features of PTC and show tumour necrosis with an high mitotic activity. In this report a further case of SV-PTC is described which was associated to Hashimoto’s thyroiditis, a finding never described in the cytological literature up to now for SV-PTC; this association created further differential diagnostic problems. The neoplasm displayed RET-PTC1 fusion.
Recurrent case of pregnancy-induced atypical haemolytic uremic syndrome (P-aHUS)
Authors: Kumar Dileep , King Mary , Jim Belinda , Acharya Anjali
Published: January 2019

Pregnancy-induced atypical haemolytic uremic syndrome (P-aHUS) is a rare condition characterised by microangiopathic haemolytic anaemia, thrombocytopenia and renal failure. It accounts for approximately 7% of total HUS cases. Here, we present a case of recurrent P-aHUS in a 25-year-old Hispanic woman. Pregnancy was the clear trigger in both instances, and the disease manifested in first week of the postpartum period. Because of her significant obstetric history, a multidisciplinary approach was adopted to monitor her second pregnancy antepartum and post partum. As the patient developed recurrence of P-aHUS 4 days after her delivery, she was immediately administered eculizumab within few hours of disease manifestation. The patient normalised her haematological parameters within 1 week but sustained dialysis-requiring renal failure for a total of 6 weeks. This case highlights the advances as well as the ongoing uncertainties, especially with respect to the use of eculizumab, in this rare but morbid disease.
Immune thrombocytopenic purpura presenting with spontaneous gingival haemorrhage in pregnancy
Authors: Dunphy Louise , Williams Rhodri
Published: January 2019

Gingival bleeding is a common intraoral finding, typically associated with inflamed tissues and periodontal disease. It is easily provoked by periodontal probing or toothbrushing. Spontaneous gingival bleeding rarely occurs and may be the only sign of systemic bleeding problems such as thrombocytopenia, leukaemia or coagulopathy. In pregnancy, acute onset of thrombocytopenia may occur in systemic disorders such as severe pre-eclampsia, HELLP syndrome (haemolysis, elevated liver enzymes, low platelets) or the acute fatty liver of pregnancy. The diagnosis and management of such conditions may challenge physicians. It requires a systematic approach with a comprehensive history to exclude causes of gingival haemorrhage such as periodontal disease, anticoagulant therapy, maxillofacial trauma, haematological disorders or a bacterial infection. The authors describe a case of immune thrombocytopenic purpura presenting with spontaneous gingival haemorrhage in pregnancy. This case highlights the fact that medical intervention to correct the underlying aberration of haemostasis is necessary for local measures to stop the gingival bleeding successfully.
Parameters affecting postoperative success of surgery for stage 4A/4B ROP
Authors: Özsaygili Cemal , Ozdek Sengul , Ozmen Mehmet Cuneyt , Atalay Hatice Tuba , Yalinbas Yeter Duygu
Published: January 2019

Purpose

To describe the long-term anatomical and functional results of surgery for retinal detachment (RD) associated with stage 4 retinopathy of prematurity (ROP) and patient and surgery-related factors affecting postoperative success.

Design

Retrospective case series at a single tertiary referral paediatric vitreoretinal practice.

Methods

One hundred and twenty-one eyes of 82 infants (40 female/42 male) who underwent lens-sparing vitrectomy (LSV) or lensectomy with vitrectomy surgery for stage 4A and 4B ROP at Gazi University Department of Ophthalmology between 2011 and 2016 were enrolled in this study. Patient characteristics including gestational age, birth weight, gender, stage of ROP at presentation, preoperative treatment (laser, anti-vascular endothelial growth factor (VEGF) or combined), anatomical and functional outcome and complications were recorded. The effect of birth weight, gestational age, presence of plus disease, preoperative treatment status, surgically induced posterior hyaloid detachment, postoperative vitreous haemorrhage and iatrogenic retinal tear formation on anatomical and functional results was evaluated.

Results

61.2% of the eyes were stage 4A and 38.8% were stage 4B ROP. The mean follow-up was 24.5 months. 18.2% of the eyes had no preoperative treatment. Anatomical success was 86.5% for stage 4A and 68.1% for stage 4B at the first year, 91.7% for stage 4A and 69.4% for stage 4B at the second year, and 95.8% for stage 4A and 57.9% for stage 4B at the third year. Functional success was 85.1% for stage 4A and 65.9% for stage 4B at the first year, 89.6% for stage 4A and 61.1% for stage 4B at the second year, and 87.5% for stage 4A and 57.8% for stage 4B at the third year. The mean visual acuity was 1.12±0.34 logarithm of the minimum angle of resolution (logMAR) for stage 4A and 1.34±0.32 logMAR at the 3-year follow-up duration (p>0.05). There was preoperative plus disease in 59.5% of the eyes. Subsequent retinal surgeries were required in 17.4% of the eyes. Presence of plus disease and absence of preoperative treatment, iatrogenic retinal tear formation and postoperative vitreous haemorrhage were found to have significant negative effects, while surgical induction of posterior hyaloid detachment and sparing the lens intraoperatively affected the anatomical and functional results positively.

Conclusions

Surgery for stage 4 ROP-associated RD resulted in encouraging anatomical and functional outcomes and the results are even better in eyes with preoperative (laser/anti-VEGF) treatment, LSV and surgically induced posterior hyaloid detachment.
Acceptability and feasibility pilot randomised controlled trial of medical skin camouflage for recovery of women prisoners with self-harm scarring (COVER): the study protocol
Authors: Mitchell Heather , Abel Kathryn M , Dunlop Brendan James , Walker Tammi , Ranote Sandeep , Robinson Louise , Edgar Fiona , Millington Tracy , Meacock Rachel , Shaw Jenny , Gutridge Kerry
Published: January 2019

Introduction

Self-harm in prison is a major public health concern. Less than 5% of UK prisoners are women, but they carry out more than a fifth of prison self-harm. Scars resulting from self-harm can be traumatising and stigmatising, yet there has been little focus on recovery of women prisoners with self-harm scarring. Medical skin camouflage (MSC) clinics treat individuals with disfiguring skin conditions, with evidence of improved well-being, self-esteem and social interactions. Only one community study has piloted the use of MSC for self-harm scarring.

Methods and analysis

We describe an acceptability and feasibility pilot randomised controlled trial; the first to examine MSC for women prisoners who self-harm. We aim to randomise 20–25 women prisoners to a 6-week MSC intervention and 20–25 to a waitlist control (to receive the MSC after the study period). We aim to train at least 6–10 long-term prisoners with personal experience of self-harm to deliver the intervention. Before and after intervention, we will pilot collection of women-centred outcomes, including quality of life, well-being and self-esteem. We will pilot collection of self-harm incidents during the intervention, resources used to manage/treat self-harm and follow-up of women at 12 weeks from baseline. Data on recruitment, retention and dropout will be recorded. We aim for the acceptability of the intervention to prison staff and women prisoners to be explored in qualitative interviews and focus groups.

Ethics and dissemination

Ethical approval for COVER has been granted by the North East–York Research Ethics Committee (REC) for phases 1 and 2 (reference: 16/NE/0030) and West of Scotland REC 3 for phases 3 and 4 (reference: 16/WS/0155). Informed consent will be the primary consideration; it will be made clear that participation will have no effect on life in prison or eligibility for parole. Due to the nature of the study, disclosures of serious self-harm may need to be reported to prison officials. We aim for findings to be disseminated via events at the study prison, presentations at national/international conferences, journal publications, prison governor meetings and university/National Health Service trust communications.

Trial registration number

NCT02638974; Pre-results.
Assessment of public oral healthcare services in Curitiba, Brazil: a cross-sectional study using the Primary Care Assessment Tool (PCATool)
Authors: Nascimento Antonio Carlos , Moysés Simone Tetü , Werneck Renata Iani , Gabardo Marilisa Carneiro Leão , Moysés Samuel Jorge
Published: January 2019

Objectives

To compare two different models of public oral health in primary care services, a so-called family health strategy (FHS), as opposed to non-FHS services designated as ‘conventional’ healthcare (CHC), regarding the presence and extent of the attributes of ‘good’ primary healthcare (PHC). The null hypothesis of this study is that the attributes do not differ between the FHS and CHC.

Design

Cross-sectional.

Setting

Public PHC services in Curitiba, the state capital of Paraná.

Participants

PHC users of the public oral health network (n=900) and dentists active in this municipal network (n=203).

Primary and secondary outcome measures

The Primary Care Assessment Tool (PCATool)-Dentists and PCATool-Users were used to analyse the primary outcomes (‘essential’ attributes) and secondary outcomes (‘derived’ attributes) in the PHC.

Results

Overall, the primary care services in oral health were well evaluated, both by users and by dentists, with mean scores ascribed to PHC attributes mostly above the cut-off point (6.6). The exception for users were affiliation (6.36; 95% CI 6.11 to 6.60) and accessibility (5.83; 95% CI 5.78 to 5.89); and for dentists the accessibility (5.80; 95% CI 5.63 to 5.96). When comparing FHS and CHC, there was a superiority of the FHS model, which reached a general mean score of 7.53 (95% CI 7.48 to 7.58) among users and 7.56 (95% CI 7.45 to 7.67) among dentists; on the other hand, the CHC general mean score was of 6.61 (95% CI 6.49 to 6.73) and 6.68 (95% CI 6.56 to 6.80) respectively for users and dentists.

Conclusions

The results reveal a reasonable level of attainment of PHC attributes in the services investigated. Nevertheless, public health managers should make efforts to reduce the difficulties faced by users in accessing dental care. The more positive results achieved by FHS services indicate that the provision of oral healthcare under this strategy should be expanded.
Association of lifestyle modification and pharmacological adherence on blood pressure control among patients with hypertension at Kenyatta National Hospital, Kenya: a cross-sectional study
Authors: Kimani Samuel , Mirie Waithira , Chege Margaret , Okube Okubatsion Tekeste , Muniu Samuel
Published: January 2019

Objective

Association of lifestyle modification and pharmacological adherence among patients with hypertension attending a national referral hospital in Kenya.

Design

Descriptive, cross-sectional.

Setting

Medical wards and outpatient clinic of a national referral hospital.

Participants

Patients (n=229) diagnosed with primary hypertension for at least 6 months.

Primary outcomes

Clinical makers, cholesterol levels, anthropometrics, lifestyle/dietary habits adjusted for age, gender and education; antihypertensive adherence; views on prevention of hypertension and adequacy of hypertension information.

Results

Ageing was associated with elevated diastolic blood pressure (BP) (p<0.05), heart rate (HR) and cholesterol. Females had higher body mass index (BMI). More males reported drinking alcohol and smoking (p<0.001), especially the highly educated. Higher BPs were observed in smokers and drinkers (p<0.05). Daily vegetables and fruits intake were linked to lower BP, HR and BMI (p<0.05). Intake of foods high in saturated fat and cholesterol were associated with raised HR (p<0.05). Respondents on antihypertensive medication, those engaged in healthy lifestyle and took their prescribed medications had lower mean BPs than those on medication only (138/85 vs 140/90). Few respondents (30.8%) considered hypertension as preventable, mainly the single and highly educated (p<0.05). Respondents (53.6%) believed they should stop taking their antihypertensive medication once hypertension is controlled.

Conclusion

Missed targets for BP control and hypertension-related risks are associated with ageing, female gender, fast food and animal fat intake. Alcohol and smoking is common in males associated with poor BP control. Daily vegetables and fruits intake are associated with better BP control and overall hypertension risk reduction. Observed suboptimal BP control despite pharmacological adherence suggests lifestyle modification is needed besides antihypertensive medication. Interventions should address modifiable risk factors aggravated by age and adverse lifestyles through adopting combined lifestyle modification, pharmacological adherence and tailored expert delivered hypertension-related information.
Combination of the National Early Warning Score (NEWS) and inflammatory biomarkers for early risk stratification in emergency department patients: results of a multinational, observational study
Authors: Eckart Andreas , Hauser Stephanie Isabelle , Kutz Alexander , Haubitz Sebastian , Hausfater Pierre , Amin Devendra , Amin Adina , Huber Andreas , Mueller Beat , Schuetz Philipp
Published: January 2019

Objectives

The National Early Warning Score (NEWS) helps to estimate mortality risk in emergency department (ED) patients. This study aimed to investigate whether the prognostic value of the NEWS at ED admission could be further improved by adding inflammatory blood markers (ie, white cell count (WCC), procalcitonin (PCT) and midregional-proadrenomedullin (MR-proADM).

Design

Secondary analysis of a multinational, observational study (TRIAGE study, March 2013–October 2014).

Setting

Three tertiary care centres in France, Switzerland and the USA.

Participants

A total of 1303 adult medical patients with complete NEWS data seeking ED care were included in the final analysis. NEWS was calculated retrospectively based on admission data.

Main outcome measures

The primary outcome was all-cause 30-day mortality. Secondary outcome was intensive care unit (ICU) admission. We used multivariate regression analyses to investigate associations of NEWS and blood markers with outcomes and area under the receiver operating curve (AUC) as a measure of discrimination.

Results

Of the 1303 included patients, 54 (4.1%) died within 30 days. The NEWS alone showed fair prognostic accuracy for all-cause 30-day mortality (AUC 0.73), with a multivariate adjusted OR of 1.26 (95% CI 1.13 to 1.40, p<0.001). The AUCs for the prediction of mortality using the inflammatory markers WCC, PCT and MR-proADM were 0.64, 0.71 and 0.78, respectively. Combining NEWS with all three blood markers or only with MR-proADM clearly improved discrimination with an AUC of 0.82 (p=0.002). Combining the three inflammatory markers with NEWS improved prediction of ICU admission (AUC 0.70vs0.65 when using NEWS alone, p=0.006).

Conclusion

NEWS is helpful in risk stratification of ED patients and can be further improved by the addition of inflammatory blood markers. Future studies should investigate whether risk stratification by NEWS in addition to biomarkers improve site-of-care decision in this patient population.

Trial registration number

NCT01768494; Post-results.
Incidence of hospitalisation for severe complications of influenza virus infection in Japanese patients between 2012 and 2016: a cross-sectional study using routinely collected administrative data
Authors: Yokomichi Hiroshi , Mochizuki Mie , Lee Joseph Jonathan , Kojima Reiji , Yokoyama Tetsuji , Yamagata Zentaro
Published: January 2019

Objective

To calculate the incidence of hospitalisation due to acute respiratory failure, pneumonia, acute respiratory distress syndrome (ARDS), febrile seizures and encephalitis/encephalopathy among influenza-positive patients in Japan, where point-of-care tests are routinely used to diagnose influenza.

Design

A cross-sectional study using routinely collected data.

Setting

Japanese clinics and hospitals between 2012 and 2016.

Participants

Japanese patients aged 0–74 years diagnosed with influenza by a rapid test in employment-related health insurance records.

Primary outcome measures

Incidence of hospitalisation per 100 000 influenza-positive episodes.

Results

We included over 16 million influenza-positive episodes, 1.0% of whom were hospitalised. Of these, 3361 were acute respiratory failure, 27 253 pneumonia, 18 ARDS, 2603 febrile seizure and 159 encephalitis/encephalopathy. The percentage of hospitalisations by age was 2.96% of patients aged 0–1 years, 0.77% aged 2–5, 0.51% aged 6–12, 0.78% aged 13–18, 1.36% aged 19–44, 1.19% aged 45–64, and 2.21% aged 65–74. The incidence of hospitalisations from these five complications combined was highest in influenza-positive patients aged 0–1 years (943 per 100 000) compared with 307 in those aged 2–5 years and 271 in those aged 65–74 years. For pneumonia, the incidence was highest for influenza-positive patients aged 0–5 years and 65 years or more. There were statistically significant decreasing trends over the years in the incidence of all-cause hospitalisations, pneumonia and febrile seizures.

Conclusions

Japanese administrative data revealed that 1.0% of influenza-positive patients aged under 75 years were hospitalised. Male patients had a higher incidence of pulmonary complications and febrile seizures. Children aged 0–5 years and adults aged 65–74 years were at high risk of being admitted to hospital for pneumonia.
Readability assessment of package leaflets of biosimilars
Authors: Piñero-López María Ángeles , Figueiredo-Escribá Carlos , Modamio Pilar , Lastra Cecilia F , Mariño Eduardo L
Published: January 2019

Objectives

To assess the degree of readability and the length of the package leaflets of biosimilars.

Setting

The package leaflets analysed were downloaded from the European Medicines Agency (EMA) website.

Participants

The study sample included the package leaflets written in English of all the biosimilars that were authorised by the EMA on 31 August 2017, and whose content was available via the internet on that date (n=35).

Design

This was a cross-sectional analytical study. The readability of the package leaflets of all biosimilars authorised by the EMA in August 2017 was determined applying the Flesch and Flesch-Kincaid formulas. The influence of the following variables on the readability and length was also analysed: package leaflet section, type of biosimilar, date of first authorisation of the biosimilar and type of medicine.

Results

A considerable variation of the package leaflets length was found (3154±803). The readability of all the package leaflets overtook the recommended value for health-related written materials taking into account Flesch-Kincaid Index, and none of the package leaflets were easy to understand according to the Flesch Index. Statistically significant differences (p<0.05) were observed between the sections of package leaflets in readability indices and length. The most difficult sections to understand were those related with the therapeutic indication of medicine and the possible side effects.

Conclusions

Package leaflets for authorised biosimilars may not fulfil the function for which they were designed. The competent organisations could be informed about the possible negative effect on the use of this type of medicines.
Unified interpretation of liver stiffness measurement by M and XL probes in non-alcoholic fatty liver disease
Authors: Wong Vincent Wai-Sun , Irles Marie , Wong Grace Lai-Hung , Shili Sarah , Chan Anthony Wing-Hung , Merrouche Wassil , Shu Sally She-Ting , Foucher Juliette , Le Bail Brigitte , Chan Wah Kheong , Chan Henry Lik-Yuen , de Ledinghen Victor
Published: January 2019

Objective

The latest model of vibration-controlled transient elastography (VCTE) automatically selects M or XL probe according to patients’ body built. We aim to test the application of a unified interpretation of VCTE results with probes appropriate for the body mass index (BMI) and hypothesise that this approach is not affected by hepatic steatosis.

Design

We prospectively recruited 496 patients with non-alcoholic fatty liver disease who underwent VCTE by both M and XL probes within 1 week before liver biopsy.

Results

391 (78.8%) and 433 (87.3%) patients had reliable liver stiffness measurement (LSM) (10 successful acquisitions and IQR:median ratio ≤0.30) by M and XL probes, respectively (p<0.001). The area under the receiver operating characteristic curves was similar between the two probes (0.75–0.88 for F2–4, 0.83–0.91 for F4). When used in the same patient, LSM by XL probe was lower than that by M probe (mean difference 2.3 kPa). In contrast, patients with BMI ≥30 kg/m2 had higher LSM regardless of the probe used. When M and XL probes were used in patients with BMI <30 and ≥30 kg/m2, respectively, they yielded nearly identical median LSM at each fibrosis stage and similar diagnostic performance. Severe steatosis did not increase LSM or the rate of false-positive diagnosis by XL probe.

Conclusion

High BMI but not severe steatosis increases LSM. The same LSM cut-offs can be used without further adjustment for steatosis when M and XL probes are used according to the appropriate BMI.
Black holes in magnetic monopoles with a dark halo
Authors: Lugo A. , Pérez Ipiña J. M. , Schaposnik F. A.
Published: January 2019

We study a spontaneously broken Einstein–Yang–Mills–Higgs model coupled via a Higgs portal to an uncharged scalar [Formula: see text]. We present a phase diagram of self-gravitating solutions showing that depending on the choice of parameters of the [Formula: see text] scalar potential and the Higgs portal coupling constant [Formula: see text], one can identify different regions: If [Formula: see text] is sufficiently small, a [Formula: see text] halo is created around the monopole core which in turn surrounds a black hole. For larger values of [Formula: see text], no halo exists and the solution is just a black hole monopole one. When the horizon radius grows and becomes larger than the monopole radius, solely a black hole solution exists. Because of the presence of the [Formula: see text] scalar, a bound for the Higgs potential coupling constant exists and when it is not satisfied, the vacuum is unstable and no nontrivial solution exists. We briefly comment on possible connections of our results with those found in recent dark matter axion models.
Holographic complexity of “black” non-susy D3-brane and the high temperature limit
Authors: Karar Sourav , Gangopadhyay Sunandan , Majumdar A. S.
Published: January 2019

The holographic complexity of a “black” non-susy D3-brane is computed. The difference in the holographic complexity between this geometry in the Fefferman–Graham coordinates and that of the AdS5 geometry is obtained for a strip-type subsystem. This is then related to the changes in the energy and the entanglement entropy of the system. We next take the high temperature limit of the change in complexity and observe that it scales with the temperature in the same way as the holographic entanglement entropy. The crossover of the holographic complexity to its corresponding thermal counterpart is similar to the corresponding crossover of the holographic entanglement entropy in the high temperature limit. We further repeat the analysis for [Formula: see text] super-Yang–Mills theory and observe a similar behavior.
A Theoretical and Numerical Analysis of the Worst-Case Size of Reduced Ordered Binary Decision Diagrams
Authors: Newton Jim , Verna Didier
Published: January 2019

Binary Decision Diagrams (BDDs) and in particular ROBDDs (Reduced Ordered BDDs) are a common data structure for manipulating Boolean expressions, integrated circuit design, type inferencers, model checkers, and many other applications. Although the ROBDD is a lightweight data structure to implement, the behavior, in terms of memory allocation, may not be obvious to the program architect. We explore experimentally, numerically, and theoretically the typical and worst-case ROBDD sizes in terms of number of nodes and residual compression ratios, as compared to unreduced BDDs. While our theoretical results are not surprising, as they are in keeping with previously known results, we believe our method contributes to the current body of research by our experimental and statistical treatment of ROBDD sizes. In addition, we provide an algorithm to calculate the worst-case size. Finally, we present an algorithm for constructing a worst-case ROBDD of a given number of variables. Our approach may be useful to projects deciding whether the ROBDD is the appropriate data structure to use, and in building worst-case examples to test their code.
Why digital systems do not reach their full potential in organizations
Authors: Sandblad Bent , Lind Thomas
Published: January 2019

The continuous evolution of digital systems shaping the workplace and the optimizing of work processes is revolutionary. But despite decades of accumulated experience, there are still plenty of projects that fail completely or deliver unexpected and unacceptable results. This article discusses why problems with the digitalization of working life persist.
Long-term testosterone deficiency modifies myofilament and calcium-handling proteins and promotes diastolic dysfunction in the aging mouse heart
Authors: Ayaz Omar , Banga Shubham , Heinze-Milne Stefan , Rose Robert A. , Pyle W. Glen , Howlett Susan E.
Published: January 2019

The impact of long-term gonadectomy (GDX) on cardiac contractile function was explored in the setting of aging. Male mice were subjected to bilateral GDX or sham operation (4 wk) and investigated at 16–18 mo of age. Ventricular myocytes were field stimulated (2 Hz, 37°C). Peak Ca2+transients (fura 2) and contractions were similar in GDX and sham-operated mice, although Ca2+transients (50% decay time: 45.2 ± 2.3 vs. 55.6 ± 3.1 ms, P < 0.05) and contractions (time constant of relaxation: 39.1 ± 3.2 vs. 69.5 ± 9.3 ms, P < 0.05) were prolonged in GDX mice. Action potential duration was increased in myocytes from GDX mice, but this did not account for prolonged responses, as Ca2+transient decay was slow even when cells from GDX mice were voltage clamped with simulated “sham” action potentials. Western blots of proteins involved in Ca2+sequestration and efflux showed that Na+/Ca2+exchanger and sarco(endo)plasmic reticulum Ca2+-ATPase type 2 protein levels were unaffected, whereas phospholamban was dramatically higher in ventricles from aging GDX mice (0.24 ± 0.02 vs. 0.86 ± 0.13, P < 0.05). Myofilament Ca2+sensitivity at physiological Ca2+was similar, but phosphorylation of essential myosin light chain 1 was reduced by ≈50% in ventricles from aging GDX mice. M-mode echocardiography showed no change in systolic function (e.g., ejection fraction). Critically, pulse-wave Doppler echocardiography showed that GDX slowed isovolumic relaxation time (12.9 ± 0.9 vs. 16.9 ± 1.0 ms, P < 0.05), indicative of diastolic dysfunction. Thus, dysregulation of intracellular Ca2+and myofilament dysfunction contribute to deficits in contraction in hearts from testosterone-deficient aging mice. This suggests that low testosterone helps promote diastolic dysfunction in the aging heart.

NEW & NOTEWORTHY The influence of long-term gonadectomy on contractile function was examined in aging male hearts. Gonadectomy slowed the decay of Ca2+transients and contractions in ventricular myocytes and slowed isovolumic relaxation time, demonstrating diastolic dysfunction. Underlying mechanisms included Ca2+dysregulation, elevated phospholamban protein levels, and hypophosphorylation of a myofilament protein, essential myosin light chain. Testosterone deficiency led to intracellular Ca2+dysregulation and myofilament dysfunction, which may facilitate diastolic dysfunction in the setting of aging.
Mouse PVRIG Has CD8+ T Cell–Specific Coinhibitory Functions and Dampens Antitumor Immunity
Authors: Murter Benjamin , Pan Xiaoyu , Ophir Eran , Alteber Zoya , Azulay Meir , Sen Rupashree , Levy Ofer , Dassa Liat , Vaknin Ilan , Fridman-Kfir Tal , Salomon Ran , Ravet Achinoam , Tam Ada , Levin Doron , Vaknin Yakir , Tatirovsky Evgeny , Machlenkin Arthur , Pardoll Drew , Ganguly Sudipto
Published: January 2019

A limitation to antitumor immunity is the dysfunction of T cells in the tumor microenvironment, in part due to upregulation of coinhibitory receptors such as PD-1. Here, we describe that poliovirus receptor–related immunoglobulin domain protein (PVRIG) acts as a coinhibitory receptor in mice. Murine PVRIG interacted weakly with poliovirus receptor (PVR) but bound poliovirus receptor–like 2 (PVRL2) strongly, making the latter its principal ligand. As in humans, murine NK and NKT cells constitutively expressed PVRIG. However, when compared with humans, less PVRIG transcript and surface protein was detected in murine CD8+ T cells ex vivo. However, activated CD8+ T cells upregulated PVRIG expression. In the mouse tumor microenvironment, infiltrating CD8+ T cells expressed PVRIG whereas its ligand, PVRL2, was detected predominantly on myeloid cells and tumor cells, mirroring the expression pattern in human tumors. PVRIG-deficient mouse CD8+ T cells mounted a stronger antigen-specific effector response compared with wild-type CD8+ T cells during acute Listeria monocytogenes infection. Furthermore, enhanced CD8+ T-cell effector function inhibited tumor growth in PVRIG−/− mice compared with wild-type mice and PD-L1 blockade conferred a synergistic antitumor response in PVRIG−/− mice. Therapeutic intervention with antagonistic anti-PVRIG in combination with anti–PD-L1 reduced tumor growth. Taken together, our results suggest PVRIG is an inducible checkpoint receptor and that targeting PVRIG–PVRL2 interactions results in increased CD8+ T-cell function and reduced tumor growth.

See related article on p. 257
A Comment on the Diagnosis and Definition of Acute Kidney Injury
Authors: Selby Nicholas M.
Published: January 2019

Context: International criteria for describing the presence and severity of acute kidney injury (AKI) based on changes in serum creatinine concentration and/or degree of oliguria are now widely accepted. Subject of Review: Three recent articles have debated the definition and diagnosis of AKI, offering conflicting opinions. On one side [Lancet 2017; 389: 779–781 and Nephrology Times 2018] an argument is made that a focus on creatinine-based staging has de-emphasised the traditional clinical approach of determining cause of AKI (pre-renal, renal or post-renal), and that any classification system based on serum creatinine is inherently flawed. The opposing argument, is that serum creatinine-based staging brings value via the consistent, robust and gradated associations between AKI stage and outcomes, and that many cases of AKI have multiple co-existing intra- and extra-renal processes that do not fit neatly into the traditional aetiological groupings [Lancet 2018; 391: 202–203]. Second Opinion: Determining the cause of AKI is a key element of clinical management, so it is important that AKI is not regarded as a single disease, rather a syndrome with multiple potential causes. This article critiques current, clinical approaches to determining AKI aetiology alongside future areas in which significant developments in patient phenotyping based on pathophysiological principles may occur. In the absence of current alternatives to serum creatinine, current AKI criteria (e.g., those from Kidney Disease Improving Global Outcomes) bring significant advantages in clinical and research environments, including facilitation of efforts to address current variations in the delivery of AKI care. However, their application needs to be accompanied by 2 aspects: an appreciation of the limitations of serum creatinine as a diagnostic test; and an absolute requirement for clinical assessment and diagnostic workup to establish the cause of AKI.
Hortiboletus kohistanensis (Boletaceae), a new bolete species from temperate and subalpine oak forests of Pakistan
Authors: NASEER AROOJ , SARWAR SAMINA , KHALID ABDUL NASIR , HEALY ROSANNE , SMITH MATTHEW E.
Published: January 2019

Hortiboletus kohistanensis is described as a new species from the moist temperate and subalpine oak forests of Pakistan after detailed morphological and phylogenetic analyses as well as comparison with related taxa. This oak-associated species is morphologically distinguished from allied taxa by an areolate pileus surface and whitish stipe base. It is also phylogenetically distinct from H. indorubellus, the most closely related species, from India.
A 1D-Var Approach to Retrieve Clear-Sky Wet Tropospheric Correction from Current and Future Altimetry Missions
Authors: Hermozo Laura , Eymard Laurence , Karbou Fatima , Picard Bruno , Pardé Mickael
Published: January 2019

Statistical methods are usually used to provide estimations of the wet tropospheric correction (WTC), necessary to correct altimetry measurements for atmospheric path delays, using brightness temperatures measured at two or three low frequencies from a passive microwave radiometer on board the altimeter mission. Despite their overall accuracy over oceanic surfaces, uncertainties still remain in specific regions of complex atmospheric stratification. Thus, there is still a need to improve the methods currently used by taking into account the frequency-dependent information content of the observations and the atmospheric and surface variations in the surroundings of the observations. In this article we focus on the assimilation of relevant passive microwave observations to retrieve the WTC over ocean using different altimeter mission contexts (current and future, providing brightness temperature measurements at higher frequencies in addition to classical low frequencies). Data assimilation is performed using a one-dimensional variational data assimilation (1D-Var) method. The behavior of the 1D-Var is evaluated by verifying its physical consistency when using pseudo- and real observations. Several observing-system simulation experiments are run and their results are analyzed to evaluate global and regional WTC retrievals. Comparisons of 1D-Var-based TWC retrieval and reference products from classical WTC retrieval algorithms or radio-occultation data are also performed to assess the 1D-Var performances.
The Influence of Goal Commitment and Partner Status on Team Assignment Outcomes
Authors: Miles Jeffrey A.
Published: January 2019

The present study replicated and extended research on the influence of team assignment methods on task performance and fairness perceptions. This study examined the influence of team assignment methods, goal commitment, and partner status on team member performance and fairness perceptions in a laboratory setting. The assignment conditions were comprised of three variables: assignment method (random, self-decision, and ability), performer status (assigned or unassigned), and partner status (unassigned team member stayed or left during task performance). A significant interaction was found between assignment method and performer status when the unassigned team member left during task performance, but not when the unassigned team member stayed. Random and self-decision assignment methods resulted in higher levels of goal commitment and task performance than did ability-based assignment conditions. Lastly, goal commitment was found to mediate the relationship between assignment method and task performance. The implications of these findings for the task performance and organizational justice literatures, as well as for managers in general, are discussed.
Prognostic significance of PCT and CRP evaluation for adult ICU patients with sepsis and septic shock: retrospective analysis of 59 cases
Authors: Cui Na , Zhang Hongwei , Chen Zhi , Yu Zhanbiao
Published: January 2019

Objective

To investigate the prognostic significance of serum procalcitonin (PCT) and C-reactive protein (CRP) in patients with sepsis and those with septic shock.

Methods

Fifty-nine patients were divided into sepsis and septic shock groups, as well as survivor and non-survivor groups, according to the severity of the disease and patient survival. Serum PCT and CRP measurements at the time of hospitalization in the intensive care unit were examined.

Results

On the 2nd, 3rd, and 5th days, the CRP level was higher in the non-survivor group than in the survivor group, and the serum CRP level was higher in patients in the septic shock group than in patients in the sepsis group. Regarding changes in serum PCT level in each group, the levels of PCT were significantly different between non-survivor and survivor groups, whereas they did not differ between patients in the sepsis and septic shock groups. Serum PCT kinetics (ΔPCT) were similar between groups.

Conclusions

Serum PCT and CRP have good clinical diagnostic and prognostic value for patients with sepsis and septic shock. Kinetic studies of PCT and CRP can improve sensitivity and accuracy when evaluating the prognosis of patients with sepsis and those with septic shock.
Spatial Distance Construal Perspectives on Cause-Related Marketing: The Importance of Nationalism in Russia
Authors: Strizhakova Yuliya , Coulter Robin A.
Published: January 2019

Consumers around the globe expect firms to contribute to environmentally and socially responsible causes. Using construal level theory with a spatial distance lens, we examine effects of spatial proximity of the firm (domestic firm vs. foreign multinational corporation [MNC]), cause (domestic vs. global), and consumer cultural identity (locally oriented: nationalism and consumer ethnocentrism; distantly oriented: global identity and global citizenship through global brands) on consumer attitudes toward the firm. Across three studies with a focus on Russia and environmental causes, we consistently find that nationalism moderates consumer attitudes, whereas consumer ethnocentrism, global identity, and global citizenship through global brands do not. When firms engage in cause-related marketing and focus on proximal causes, nationalistic consumers are more favorable toward domestic firms (vs. foreign MNCs). When firms are not engaged in cause-related marketing, consumers with stronger nationalism are more favorable toward domestic firms, and consumers with weaker nationalism are more favorable toward foreign MNCs. Importantly, the effects of nationalism are mitigated when foreign MNCs and domestic firms engage with global causes. Product involvement, environmental concerns, and marketplace skepticism are predictors of attitudes toward the firm. The results highlight the importance of considering the socio-historical-political context of a given country and locally oriented nationalistic beliefs.
Ointment Pseudo-Cheilitis: A Disease Distinct From Factitial Cheilitis. A Series of 13 Patients From São Paulo, Brazil
Authors: Nico Marcello Menta Simonsen , Dwan Alexandre Jack , Lourenço Silvia Vanessa
Published: January 2019

Background:

The terms exfoliative cheilitis, factitial cheilitis, and morsicatio labiorum are used to describe self-inflicted lesions of the lip.

Objective:

Here we report and analyze clinical, pathological, and therapeutic data on 13 patients with a form of factitial cheilitis that we believe should be considered a separate entity.

Results:

Eight patients were male and 5 patients were female. All patients reported pain and presented with crusts consisting of dried saliva and topical medications adherent to the surface of the lips. These patients expressed great concern with their condition, and reported several previous, ineffective treatments. Simple reassurance only was not effective; saline compresses alleviated symptoms for a few patients. Most patients were lost to follow-up. Biopsies were not performed on all patients.

Conclusion:

This particular type of cheilitis artefacta has been previously described, but some features described herein are new and allow a specific approach: patient’s behavior, the “protrusion sign,” and possible improvement with antidepressants. For these cases, we propose the term ointment pseudo-cheilitis because it comprises the nature of the attached material and the lack of true inflammation. Further psychiatric characterization is a logical next step in further characterizing this difficult-to-treat condition.