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Background: Biallelic variants in POLR1C are associated with POLR3-related leukodystrophy (POLR3-HLD), or 4H leukodystrophy (Hypomyelination, Hypodontia, Hypogonadotropic Hypogonadism), and Treacher Collins syndrome (TCS). The clinical spectrum of POLR3-HLD caused by variants in this gene has not been described. Methods: A cross-sectional observational study involving 25 centers worldwide was conducted between 2016 and 2018. The clinical, radiologic and molecular features of 23 unreported and previously reported cases of POLR3-HLD caused by POLR1C variants were reviewed. Results: Most participants presented between birth and age 6 years with motor difficulties. Neurological deterioration was seen during childhood, suggesting a more severe phenotype than previously described. The dental, ocular and endocrine features often seen in POLR3-HLD were not invariably present. Five patients (22%) had a combination of hypomyelinating leukodystrophy and abnormal craniofacial development, including one individual with clear TCS features. Several cases did not exhibit all the typical radiologic characteristics of POLR3-HLD. A total of 29 different pathogenic variants in POLR1C were identified, including 13 new disease-causing variants. Conclusions: Based on the largest cohort of patients to date, these results suggest novel characteristics of POLR1C-related disorder, with a spectrum of clinical involvement characterized by hypomyelinating leukodystrophy with or without abnormal craniofacial development reminiscent of TCS.
Lateral memristors consisting of planar Ag electrodes (with sub-micrometer separation) supported on thin films of amorphous zinc-tin-oxide have been characterized. After an initial filament-forming process, each device exhibited volatile, resistive switching. In the low resistance state, the transport mechanism and conductance depended on prior activity and on the imposed current limit, mimicking biologic synaptic plasticity. Microscopic observations performed on each device revealed nanoscale filaments between the electrodes. These filaments were subject to Rayleigh instability and exhibited relaxation times determined by their effective radii. The relaxation times and on:off resistance ratios suggest suitability for threshold switching selector devices.
To assess general medical residents’ familiarity with antibiograms using a self-administered survey
Cross-sectional, single-center survey
Residents in internal medicine, family medicine, and pediatrics at an academic medical center
Participants were administered an anonymous survey at our institution during regularly scheduled educational conferences between January and May 2012. Questions collected data regarding demographics, professional training; further open-ended questions assessed knowledge and use of antibiograms regarding possible pathogens, antibiotic regimens, and prescribing resources for 2 clinical vignettes; a series of directed, closed-ended questions followed. Bivariate analyses to compare responses between residency programs were performed.
Of 122 surveys distributed, 106 residents (87%) responded; internal medicine residents accounted for 69% of responses. More than 20% of residents could not accurately identify pathogens to target with empiric therapy or select therapy with an appropriate spectrum of activity in response to the clinical vignettes; correct identification of potential pathogens was not associated with selecting appropriate therapy. Only 12% of respondents identified antibiograms as a resource when prescribing empiric antibiotic therapy for scenarios in the vignettes, with most selecting the UpToDate online clinical decision support resource or The Sanford Guide. When directly questioned, 89% reported awareness of institutional antibiograms, but only 70% felt comfortable using them and only 44% knew how to access them.
When selecting empiric antibiotics, many residents are not comfortable using antibiograms as part of treatment decisions. Efforts to improve antibiotic use may benefit from residents being given additional education on both infectious diseases pharmacotherapy and antibiogram utilization.
Synchronisation of the received Pseudorandom (PRN) code and its locally generated replica is fundamental when estimating user position in Global Navigation Satellite System (GNSS) receivers. It has been observed through experiments that user position accuracy decreases if sampling frequency is an integer multiple of the nominal code rate. This paper provides an accuracy analysis based on the number of samples and the residual code phase of each code chip. The outcomes reveal that the distribution of residual code phases in the code phase range [0, 1/ns), where ns is the number of samples per code chip, is the root cause of accuracy degradation, rather than the ratio between sampling frequency and nominal code rate. Doppler frequencies, coherent integration periods, front-end filter bandwidths and received Carrier to Noise ratios (C/N0) also influence receiver accuracy. Also provided are a sampling frequency selection guideline and new proposed estimates of the correlation output and the Delay Locked Loop (DLL) tracking error, which can be applied to precisely model GNSS receiver baseband signal processing.
Central nervous system infections (CNSI) are a leading cause of death and long-term disability in children. Using ICD-10 data from 2005 to 2015 from three central hospitals in Ho Chi Minh City (HCMC), Vietnam, we exploited generalized additive mixed models (GAMM) to examine the spatial-temporal distribution and spatial and climatic risk factors of paediatric CNSI, excluding tuberculous meningitis, in this setting. From 2005 to 2015, there were 9469 cases of paediatric CNSI; 33% were ⩽1 year old at admission and were mainly diagnosed with presumed bacterial CNSI (BI) (79%), the remainder were >1 year old and mainly diagnosed with presumed non-bacterial CNSI (non-BI) (59%). The urban districts of HCMC in proximity to the hospitals as well as some outer districts had the highest incidences of BI and non-BI; BI incidence was higher in the dry season. Monthly BI incidence exhibited a significant decreasing trend over the study. Both BI and non-BI were significantly associated with lags in monthly average temperature, rainfall, and river water level. Our findings add new insights into this important group of infections in Vietnam, and highlight where resources for the prevention and control of paediatric CNSI should be allocated.
We sought to comprehensively assess the prevalence and outcomes of complications associated with Staphylococcus aureus bacteremia (SAB) in children. Secondarily, prevalence of methicillin resistance and outcomes of complications from methicillin-resistant S. aureus (MRSA) vs. methicillin-susceptible S. aureus SAB were assessed. This is a single-center cross-sectional study of 376 patients ⩽18 years old with SAB in 1990–2014. Overall, 197 (52%) patients experienced complications, the most common being osteomyelitis (33%), skin and soft tissue infection (31%), and pneumonia (25%). Patients with complications were older (median 3 vs. 0·7 years, P = 0·05) and more had community-associated SAB (66% vs. 34%, P = 0·001). Fewer patients with complications had a SAB-related emergency department or hospital readmission (10% vs. 19%, P = 0·014). Prevalence of methicillin resistance increased from 1990–1999 to 2000–2009, but decreased in 2010–2014. Complicated MRSA bacteremia resulted in more intensive care unit admissions (66% vs. 47%, P = 0·03) and led to increased likelihood of having ⩾2 foci (58% vs. 26%, P < 0·001). From multivariate analysis, community-associated SAB increased risk and concurrent infections decreased risk of complications (odds ratio (OR) 1·82 (1·1–3·02), P = 0·021) and (OR 0·58 (0·34–0·97), P = 0·038), respectively. In conclusion, children with SAB should be carefully evaluated for complications. Methicillin resistance remains associated with poor outcomes but have decreased in overall prevalence.
Increased intestinal permeability (IP) can lead to compromised health. Limited in vivo IP research has been conducted in chickens. The objectives of the current study were to develop a model of increased IP utilizing lipopolysaccharide (LPS Escherichia coli O55:B5) and to evaluate IP changes using the lactulose, mannitol and rhamnose (LMR) sugar permeability test. In addition, fluorescein isothiocyanate dextran (FITC-d), d-lactate, zonula occludens (ZO-1) and diamine oxidase (DAO) permeability tests were employed. Male Ross chickens were reared until day 14 on the floor in an animal care facility and then transferred to individual cages in three separate experiments. In each of experiments 1 and 2, 36 chicks were randomly allocated to receive either saline (control) or LPS (n=18/group). Lactulose, mannitol and rhamnose sugar concentration in blood was measured at 0, 30, 60, 90, 120 and 180 min in experiment 1, at 60, 90 and 120 min in experiment 2 and at 90 min in experiment 3 (n=16/group). Lipopolysaccharide was injected intraperitoneally at doses of 0.5, 1 and 1 mg/kg BW in experiments 1, 2 and 3, respectively, on days 16, 18 and 20, whereas control received sterile saline. On day 21, only birds in experiments 1 and 2 were fasted for 19.5 h. Chicks were orally gavaged with the LMR sugars (0.25 gL, 0.05 gM, 0.05 gR/bird) followed by blood collection (from the brachial vein) as per time point for each experiment. Only in experiment 3, were birds given an additional oral gavage of FITC-d (2.2 mg/ml per bird) 60 min after the first gavage. Plasma d-lactate, ZO-1 and DAO concentrations were also determined by ELISA in experiment 3 (n=10). Administration of LPS did not affect IP as measured by the LMR sugar test compared with control. This was also confirmed by FITC-d and DAO levels in experiment 3 (P>0.05). The plasma levels of d-lactate were decreased (P<0.05). Plasma levels of ZO-1 were increased in the third experiment only and did not change in the first two experiments. Lipopolysaccharide at doses of 0.5 and 1 mg/kg did not increase IP in this model system. In conclusion, the LMR sugar can be detected in blood 90 min after the oral gavage. Further studies are needed for the applicability of LMR sugars tests.
Carbonated calcium apatites doped with a monovalent cation (Li+, Na+, or K+) or a divalent cation (Mg2+ or Zn2+) were prepared in aqueous solution and analysed by powder X-ray diffraction, inductively coupled plasma atomic emission spectroscopy and infrared spectroscopy. The hypothesis that the location of carbonate in the apatite structure, either in place of hydroxide ions in the c-axis channels (A-type substitution) or in place of phosphate (B-type substitution), is affected by the solution energetics of the cation (specifically its enthalpy of hydration) was strengthened by the observation of larger amounts of Atype carbonate in apatites containing the monovalent cations in aqueous solution. It is shown that cations with low negative enthalpies of hydration favour A-type substitution, whereas cations with higher negative hydration enthalpies, such as divalent cations (Mg2+, Zn2+), favour B-type substitution.
High rates of immigration from endemic countries contribute to the high chronic hepatitis B (HBV) prevalence in New York City (NYC) compared to the United States overall, i.e. about 1 million individuals. We describe the impact of HBV infection on mortality and specific causes of death in NYC. We matched surveillance and vital statistics mortality data collected from 2000 to 2011 by the New York City Department of Health and Mental Hygiene (DOHMH) and analysed demographics and premature deaths (i.e. whether death occurred at <65 years) in persons with and without chronic HBV or HIV infection (excluding those with hepatitis C). From 2000 to 2011, a total of 588 346 adults died in NYC. Of all decedents, 568 753 (97%) had no report of HIV or HBV, and 4346 (0·7%) had an HBV report. Of HBV-infected decedents, 1074 (25%) were HIV co-infected. Fifty-five percent of HBV mono-infected and 95% of HBV/HIV co-infected decedents died prematurely. HBV disproportionately impacts two subgroups: Chinese immigrants and HIV-infected individuals. These two subgroups are geographically clustered in different neighbourhoods of NYC. Tailoring prevention and treatment messages to each group is necessary to reduce the overall burden of HBV in NYC.