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A piezoelectric biomedical microelectromechanical system (bioMEMS) cantilever device was designed and fabricated to act as either a sensing element for muscle tissue contraction or as an actuator to apply mechanical force to cells. The sensing ability of the piezoelectric cantilevers was shown by monitoring the electrical signal generated from the piezoelectric aluminum nitride in response to the contraction of iPSC-derived cardiomyocytes cultured on the piezoelectric cantilevers. Actuation was demonstrated by applying electrical pulses to the piezoelectric cantilever and observing bending via an optical detection method. This piezoelectric cantilever device was designed to be incorporated into body-on-a-chip systems.
Antibiotics are widely used by all specialties in the hospital setting. We evaluated previously defined high-risk antibiotic use in relation to Clostridioides difficile infections (CDIs).
We analyzed 2016–2017 data from 171 hospitals. High-risk antibiotics included second-, third-, and fourth-generation cephalosporins, fluoroquinolones, carbapenems, and lincosamides. A CDI case was a positive stool C. difficile toxin or molecular assay result from a patient without a positive result in the previous 8 weeks. Hospital-associated (HA) CDI cases included specimens collected >3 calendar days after admission or ≤3 calendar days from a patient with a prior same-hospital discharge within 28 days. We used the multivariable Poisson regression model to estimate the relative risk (RR) of high-risk antibiotic use on HA CDI, controlling for confounders.
The median days of therapy for high-risk antibiotic use was 241.2 (interquartile range [IQR], 192.6–295.2) per 1,000 days present; the overall HA CDI rate was 33 (IQR, 24–43) per 10,000 admissions. The overall correlation of high-risk antibiotic use and HA CDI was 0.22 (P = .003), and higher correlation was observed in teaching hospitals (0.38; P = .002). For every 100-day (per 1,000 days present) increase in high-risk antibiotic therapy, there was a 12% increase in HA CDI (RR, 1.12; 95% CI, 1.04–1.21; P = .002) after adjusting for confounders.
High-risk antibiotic use is an independent predictor of HA CDI. This assessment of poststewardship implementation in the United States highlights the importance of tracking trends of antimicrobial use over time as it relates to CDI.
Dementia, a term that describes a variety of brain conditions marked by gradual, persistent and progressive cognitive decline, affects a significant proportion of older adults. Older adults with dementia are sometimes perceived less favourably than those without dementia. Furthermore, compared to persons without dementia, those with dementia are often perceived by others as having reduced personhood. This study was aimed at investigating whether differences in attitudes towards dementia and personhood perceptions vary as a function of age group, care-giver status, attitudes towards ageing, dementia knowledge, gender and education. In total 196 younger, middle-aged and older adults were recruited. Findings revealed that being a care-giver as well as having less ageist attitudes were predictive of being more comfortable around persons with dementia, having more knowledge about dementia and ascribing greater personhood to people with dementia. Those with more dementia knowledge (prior to the study) were less comfortable around people with dementia. Finally, when controlling this prior dementia knowledge, older adults were more comfortable around people with dementia compared to younger and middle-aged adults. Gender and education were not associated with any of the variables under study. Findings contribute to a better understanding of the role of age- and care-giver-related factors in the determination of attitudes towards dementia.
Dietary quality (DQ), as assessed by the Alternative Healthy Eating Index for Pregnancy (AHEI-P), and conception and pregnancy outcomes were evaluated.
In this prospective cohort study on couples planning their first pregnancy. Cox proportional hazards regression assessed the relationship between AHEI-P score and clinical pregnancy, live birth and pregnancy loss.
Participants were recruited from the Northeast region of the USA.
Participants: Healthy, nulliparous couples (females, n 132; males, n 131; one male did not enrol).
There were eighty clinical pregnancies, of which sixty-nine resulted in live births and eleven were pregnancy losses. Mean (sd) female AHEI-P was 71·0 (13·7). Of those who achieved pregnancy, those in the highest tertile of AHEI-P had the greatest proportion of clinical pregnancies; however, this association was not statistically significant (P = 0·41). When the time it took to conceive was considered, females with the highest AHEI-P scores were 20 % and 14 % more likely to achieve clinical pregnancy (model 1: hazard ratio (HR) = 1·20; 95 % CI 0·66, 2·17) and live birth (model 1: HR = 1·14; 95 % CI 0·59, 2·20), respectively. Likelihood of achieving clinical pregnancy and live birth increased when the fully adjusted model, including male AHEI-P score, was examined (clinical pregnancy model 4: HR = 1·55; 95 % CI 0·71, 3·39; live birth model 4: HR = 1·36; 95 % CI 0·59, 3·13).
The present study is the first to examine AHEI-P score and achievement of clinical pregnancy. DQ was not significantly related to pregnancy outcomes, even after adjustments for covariates.
Grape marc (GPM) is a viticulture by-product that is rich in secondary compounds, including condensed tannins (CT), and is used as a supplement in livestock feeding practices. The aim of this study was to determine whether feeding GPM to lactating dairy cows would alter the milk proteome through changes in nitrogen (N) partitioning. Ten lactating Holstein cows were fed a total mixed ration (TMR) top-dressed with either 1.5 kg dry matter (DM)/cow/day GPM (GPM group; n = 5) or 2.0 kg DM/cow/day of a 50:50 beet pulp: soy hulls mix (control group; n = 5). Characterization of N partitioning and calculation of N partitioning was completed through analysis of plasma urea-N, urine, feces, and milk urea-N. Milk samples were collected for general composition analysis, HPLC quantification of the high abundance milk proteins (including casein isoforms, α-lactalbumin, and β-lactoglobulin) and liquid chromatography tandem mass spectrometry (LC-MS/MS) analysis of the low abundance protein enriched milk fraction. No differences in DMI, N parameters, or calculated N partitioning were observed across treatments. Dietary treatment did not affect milk yield, milk protein or fat content or yield, or the concentrations of high abundance milk proteins quantified by HPLC analysis. Of the 127 milk proteins that were identified by LC-MS/MS analysis, 16 were affected by treatment, including plasma proteins and proteins associated with the blood-milk barrier, suggesting changes in mammary passage. Immunomodulatory proteins, including butyrophilin subfamily 1 member 1A and serum amyloid A protein, were higher in milk from GPM-fed cows. Heightened abundance of bioactive proteins in milk caused by dietary-induced shifts in mammary passage could be a feasible method to enhance the healthfulness of milk for both the milk-fed calf and human consumer. Additionally, the proteome shifts observed in this trial could provide a starting point for the identification of biomarkers suitable for use as indicators of mammary function.
ALKS 3831, currently under development for the treatment of schizophrenia, is composed of olanzapine (OLZ) and a fixed dose of 10mg of samidorphan. In a Phase 2 study in stable patients with schizophrenia, ALKS 3831mitigated OLZ-associated weight gain while maintaining an antipsychotic efficacy profile similar to OLZ.
To assess the efficacy and safety of ALKS 3831 in patients with acute exacerbation of schizophrenia.
This was a Phase 3, 4-week, randomized, double-blind, active and placebo (PBO)-controlled study of ALKS 3831 in patients with acute exacerbation of schizophrenia (ClinicalTrials.gov: NCT02634346). Eligible patients (N=403) were randomized 1:1:1 to receive ALKS 3831, OLZ, or PBO. Patients were treated in an inpatient setting for the first 2weeks of the study and could be treated as inpatients or outpatients for the remaining 2weeks. Patients were excluded if they received OLZ within 6months prior to screening. Antipsychotic efficacy was assessed using the Positive and Negative Syndrome Scale (PANSS), and Clinical Global Impression–Severity (CGI-S) and CGI–Improvement (CGI-I) scales. Safety and tolerability were assessed as adverse events (AEs).
Of 401 randomized patients who received ALKS 3831, OLZ, or PBO, 91%, 89%, and 83% of patients, respectively, completed treatment. The most common reason for discontinuation was withdrawal by patient (6% in both the ALKS 3831and PBO groups, and 7% in the OLZ group). Baseline characteristics were generally similar between groups; however, baseline mean body mass index was higher in the OLZ group than in the ALKS 3831 group. Baseline mean±standard deviation scores were 101.7±11.9 for PANSS total score and 5.1±0.7 for CGI-S scale score. The mean OLZ dose was 18.4mg/day in both active treatment arms. Least squares (LS) mean difference±standard error (SE) vs PBO from baseline to Week 4 in PANSS total score was –6.4±1.8 (P<.001) for the ALKS 3831 group and –5.3±1.8 (P=.004) for the OLZ group. LS mean difference±SE vs PBO from baseline to Week 4 in CGI-S scale score was −0.4±0.1 (P=.002) for the ALKS3831 group and −0.4±0.1 (P<.001) for the OLZ group. The percentage of patients with improvement in PANSS response (≥30% from baseline) at Week 4 was 60%, 54%, and 38% in the ALKS 3831, OLZ, and PBO groups, respectively. The percentage of patients with an improvement in CGI-I scale response (score of ≤2) at Week 4 was 58%, 51%, and 33% in the ALKS 3831, OLZ, and PBO groups, respectively. Discontinuation due to AEs was low in all groups. Common AEs (≥5% in any group) included weight gain, somnolence, dry mouth, anxiety, headache, and schizophrenia.
Treatment with ALKS 3831 was more effective than PBO, as measured by the PANSS and CGI-S scale, and its antipsychotic efficacy was similar to the active control OLZ. The safety profile of ALKS 3831 was similar toOLZ.
Funding Acknowledgements: This study was funded by Alkermes, Inc.
Task-specific dystonia is characterized by abnormal repetitive movements or postures in a specific body part that is triggered and ends with a task, such as writing. Failing medications, surgery, specifically disruption of key nuclei in the thalamus, can provide excellent symptomatic relief. Transcranial magnetic resonance (MR)-guided focused ultrasound is an emerging incision-less thermoablation technique. We describe MR-guided focused ultrasound tandem ablation of the ventral intermediate and ventralis oralis posterior nuclei in a 60-year-old patient with writer’s cramp. The clinical improvement was immediate with incremental benefit from the latter lesion, which was sustained at 6 months follow-up.
The detection of organic molecules that are indicative of past or present biological activity within the Solar System bodies and beyond is a key research area in astrobiology. Mars is of particular interest in this regard because of evidence of a (perhaps transient) warm and wet climate in its past. To date, space missions to Mars have primarily used pyrolysis technique to extract organic compounds from the Martian regolith, but it has not enabled a clear detection of unaltered native Martian organics. The elevated temperatures required for pyrolysis extraction can cause native Martian organics to react with perchlorate salts in the regolith, possibly resulting in the chlorohydrocarbons that have been detected by mass spectrometry, a commonly used in situ technique for space applications. Supercritical carbon dioxide (SCCO2) extraction technique is a powerful alternative to pyrolysis that may be capable of extracting and delivering unaltered native organic species to an analyser. In this study, we report the SCCO2 extraction of unaltered amino acids (AAs) with simple laboratory analyses of extracts by capillary electrophoresis laser-induced fluorescence (CE/LIF) and liquid chromatography with mass spectrometry (LC/MS) techniques. The extraction efficiencies of several representative AAs using SCCO2 with small amounts of pure water (~1–5%) as a co-solvent were determined. Glass beads were used as a model substrate to examine the effects of several experimental parameters and Johnson Space Center (JSC) Mars-1A Martian regolith simulant was used to study the effect of complex matrix on extraction efficiencies. With optimized experimental conditions (75C and 5% of water), extraction efficiencies from doped JSC Mars-1A were found to be ~40% for glycine, alanine and serine and ~10% for lysine. Extraction of native organics from undoped JSC Mars-1A suggests that SCCO2/water solvent system can extract both organics extractable with pure SCCO2 and those extractable with pure water. Additionally, species not extracted by either pure SCCO2 or pure water were extracted with SCCO2/water solvent. Despite the preliminary nature of this work, it paves the path for more comprehensive extraction studies of astrobiologically relevant samples with thorough analyses of resulting extracts.
Enterovirus A-71 (EV-A71) may be fatal, but the natural history, symptoms, and signs are poorly understood. This study aimed to examine the natural history of fatal EV-A71 infection and to identify the symptoms and signs of early warning of deterioration. This was a clinical observational study of fatal cases of EV-A71 infection treated at five Chinese hospitals between 1 January 2010 and 31 December 2012. We recorded and analysed 91 manifestations of EV-A71 infection in order to identify early prognosis indicators. There were 54 fatal cases. Median age was 21.5 months (Q1−Q3: 12–36). The median duration from onset to death was 78.5 h (range, 6 to 432). The multilayer perceptron analysis showed that ataxia respiratory, ultrahyperpyrexia, excessive tachycardia, refractory shock, absent pharyngeal reflex, irregular respiratory rhythm, hyperventilation, deep coma, pulmonary oedema and/or haemorrhage, excessive hypertension, tachycardia, somnolence, CRT extension, fatigue or sleepiness and age were associated with death. Autopsy findings (n = 2) showed neuronal necrosis, softening, perivascular cuffing, colloid and neuronophagia phenomenon in the brainstem. The fatal cases of enterovirus A71 had neurologic involvement, even at the early stage. Direct virus invasion through the neural pathway and subsequent brainstem damage might explain the rapid progression to death.
Nanopore tuning via atomic layer deposition (ALD) is promising but its conformality on sub-10nm pores and its homogeneity over the whole porous network is still challenging, primarily due to the slow transport within the porous network. Conventional ALD process oftentimes falls into a dilemma: higher temperature and prolonged exposure/purge time are required to overcome the slow transport issue, but higher temperature will cause the instability of surface –OH groups and prolonged exposure/purge time will result in “over purge” at the surface vicinity, leading to another type of non-homogeneity. To resolve this issue, a new dual-stage exposure/purge ALD process was developed. Each exposure/purge step contains a longer exposure/purge stage and a shorter exposure/purge stage, where the longer stage ensures ideal exposure/purge for inner pores, and the shorter stage makes up the surface depletion for the outer pores. By doing so, we’ve been able to extend the ALD nanopore tuning to sub-10nm pores with excellent coating homogeneity and conformality.
The brain-derived neurotrophic factor (BDNF) Val66Met polymorphism Met allele exacerbates amyloid (Aβ) related decline in episodic memory (EM) and hippocampal volume (HV) over 36–54 months in preclinical Alzheimer's disease (AD). However, the extent to which Aβ+ and BDNF Val66Met is related to circulating markers of BDNF (e.g. serum) is unknown. We aimed to determine the effect of Aβ and the BDNF Val66Met polymorphism on levels of serum mBDNF, EM, and HV at baseline and over 18-months.
Non-demented older adults (n = 446) underwent Aβ neuroimaging and BDNF Val66Met genotyping. EM and HV were assessed at baseline and 18 months later. Fasted blood samples were obtained from each participant at baseline and at 18-month follow-up. Aβ PET neuroimaging was used to classify participants as Aβ– or Aβ+.
At baseline, Aβ+ adults showed worse EM impairment and lower serum mBDNF levels relative to Aβ- adults. BDNF Val66Met polymorphism did not affect serum mBDNF, EM, or HV at baseline. When considered over 18-months, compared to Aβ– Val homozygotes, Aβ+ Val homozygotes showed significant decline in EM and HV but not serum mBDNF. Similarly, compared to Aβ+ Val homozygotes, Aβ+ Met carriers showed significant decline in EM and HV over 18-months but showed no change in serum mBDNF.
While allelic variation in BDNF Val66Met may influence Aβ+ related neurodegeneration and memory loss over the short term, this is not related to serum mBDNF. Longer follow-up intervals may be required to further determine any relationships between serum mBDNF, EM, and HV in preclinical AD.
A group of traditional pottery workshops in Sichuan Province, China, produce a unique coal-clay composite ceramic that is fired using a similarly unique kiln design and two-stage firing procedure not seen in any other ceramic tradition. Here we report on field and laboratory efforts to better understand this unusual ceramic material and technology, the functional advantages as cookware, braziers, and large storage vessels that include high strength and high thermal shock resistance, and the cultural context that supported the creativity and experimentation needed to develop such an innovative technology.
Unusual raw materials are used to produce Tibetan black pottery in Puma township of Derge County, Sichuan Province, China. Carbonaceous, calcareous pyrite-rich illitic lakebed clay is mixed in equal proportions with a ferruginous talc-chlorite steatite. A two-stage firing process results in a dark, lustrous surface. The large amount of talc imparts many useful functional qualities to this pottery; most significant are the low thermal expansion and good thermal conduction properties of talc that make these ceramics highly suitable for heating and cooking in this high mountain region. Although used in some modern ceramics, and even in modern stoves, talc is an unusual ingredient in non-industrialized ceramics. Procurement and preparation of this resource adds to the production time but its properties and performance make talc an excellent choice for the well-being and comfort of local Tibetan households.
Anthrax is still a severe public health problem and threat to human health. A cutaneous anthrax outbreak occurred in Jiangsu Province, a non-endemic anthrax region of eastern China, from July to August 2012. Epidemiological and laboratory investigation were initiated to trace the source of infection and identify the risk factors of the outbreak. On 25 July 2012, 17 persons were exposed to a sick cow, which had been imported from northeast China a few days previously. Of the 17 exposed, eight developed symptoms between 1 and 8 days and were diagnosed as cutaneous anthrax cases. Three main genes of Bacillus anthracis were detected from both human and cow meat samples, indicating that the outbreak was associated with this infected cow. A retrospective cohort study showed that contact with blood and presence of skin damage contributed to the case infection with B. anthracis. The outbreak highlights the need to enhance quarantine for imported livestock, which should have been vaccinated prior to importation, the significance of education for high-risk individuals, and training for primary healthcare workers even in anthrax-free areas.
Epidemiological studies have identified increased colorectal cancer (CRC) risk with high red meat (HRM) intakes, whereas dietary fibre intake appears to be protective. In the present study, we examined whether a HRM diet increased rectal O6-methyl-2-deoxyguanosine (O6MeG) adduct levels in healthy human subjects, and whether butyrylated high-amylose maize starch (HAMSB) was protective. A group of twenty-three individuals consumed 300 g/d of cooked red meat without (HRM diet) or with 40 g/d of HAMSB (HRM+HAMSB diet) over 4-week periods separated by a 4-week washout in a randomised cross-over design. Stool and rectal biopsy samples were collected for biochemical, microbial and immunohistochemical analyses at baseline and at the end of each 4-week intervention period. The HRM diet increased rectal O6MeG adducts relative to its baseline by 21 % (P< 0·01), whereas the addition of HAMSB to the HRM diet prevented this increase. Epithelial proliferation increased with both the HRM (P< 0·001) and HRM+HAMSB (P< 0·05) diets when compared with their respective baseline levels, but was lower following the HRM+HAMSB diet compared with the HRM diet (P< 0·05). Relative to its baseline, the HRM+HAMSB diet increased the excretion of SCFA by over 20 % (P< 0·05) and increased the absolute abundances of the Clostridium coccoides group (P< 0·05), the Clostridiumleptum group (P< 0·05), Lactobacillus spp. (P< 0·01), Parabacteroides distasonis (P< 0·001) and Ruminococcus bromii (P< 0·05), but lowered Ruminococcus torques (P< 0·05) and the proportions of Ruminococcus gnavus, Ruminococcus torques and Escherichia coli (P< 0·01). HRM consumption could increase the risk of CRC through increased formation of colorectal epithelial O6MeG adducts. HAMSB consumption prevented red meat-induced adduct formation, which may be associated with increased stool SCFA levels and/or changes in the microbiota composition.
Background: Global variation in the incidence of multiple sclerosis (MS) is generally ascribed to differences in genetic and environmental risk factors. Here we investigate temporal trends in the incidence of MS and related disorders in British Columbia, Canada, from 1986 to 2010, focusing particularly on the Asian ethnic subpopulation.
Methods: A longitudinal database was screened to identify newly diagnosed cases of MS and related disorders, including neuromyelitis optica and clinically isolated syndromes. Age-standardized, sex-specific mean annual incidence was calculated for the Asian and non-Asian population of British Columbia for 5-year intervals from 1986 to 2010. Temporal changes and cohort differences in incidence rates and demographic characteristics were evaluated. Results: During this period, the incidence of MS and related disorders in the non-Asian population remained relatively unchanged, from 10.41 (95% confidence interval [CI]: 9.87-10.97) to 9.91 (95% CI: 9.46-10.39) per 100,000 (p=0.167). In contrast, incidence in the Asian population doubled during the same period. This increase was driven by a precipitous rise in the incidence of MS in females from 0.71 (95% CI: 0.01-1.50) to 2.08 (95% CI: 1.43-2.91) per 100,000 (p=0.004), including both Canadian-born and immigrant Asians. The incidence of neuromyelitis optica did not change significantly during this period. Conclusions: The incidence of MS may be increasing among females in the Asian ethnic population of British Columbia.
To predict the likelihood of hospital-onset Clostridium difficile infection (HO-CDI) based on patient clinical presentations at admission
Retrospective data analysis
Six US acute care hospitals
We used clinical data collected at the time of admission in electronic health record (EHR) systems to develop and validate a HO-CDI predictive model. The outcome measure was HO-CDI cases identified by a nonduplicate positive C. difficile toxin assay result with stool specimens collected >48 hours after inpatient admission. We fit a logistic regression model to predict the risk of HO-CDI. We validated the model using 1,000 bootstrap simulations.
Among 78,080 adult admissions, 323 HO-CDI cases were identified (ie, a rate of 4.1 per 1,000 admissions). The logistic regression model yielded 14 independent predictors, including hospital community onset CDI pressure, patient age ≥65, previous healthcare exposures, CDI in previous admission, admission to the intensive care unit, albumin ≤3 g/dL, creatinine >2.0 mg/dL, bands >32%, platelets ≤150 or >420 109/L, and white blood cell count >11,000 mm3. The model had a c-statistic of 0.78 (95% confidence interval [CI], 0.76–0.81) with good calibration. Among 79% of patients with risk scores of 0–7, 19 HO-CDIs occurred per 10,000 admissions; for patients with risk scores >20, 623 HO-CDIs occurred per 10,000 admissions (P<.0001).
Using clinical parameters available at the time of admission, this HO-CDI model demonstrated good predictive ability, and it may have utility as an early risk identification tool for HO-CDI preventive interventions and outcome comparisons.