To send content items to your account,
please confirm that you agree to abide by our usage policies.
If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your account.
Find out more about sending content to .
To send content items to your Kindle, first ensure firstname.lastname@example.org
is added to your Approved Personal Document E-mail List under your Personal Document Settings
on the Manage Your Content and Devices page of your Amazon account. Then enter the ‘name’ part
of your Kindle email address below.
Find out more about sending to your Kindle.
Note you can select to send to either the @free.kindle.com or @kindle.com variations.
‘@free.kindle.com’ emails are free but can only be sent to your device when it is connected to wi-fi.
‘@kindle.com’ emails can be delivered even when you are not connected to wi-fi, but note that service fees apply.
Innovation Concept: The fairness of the Canadian Residency Matching Service (CaRMS) selection process has been called into question by rising rates of unmatched medical students and reports of bias and subjectivity. We outline how the University of Saskatchewan Royal College emergency medicine program evaluates CaRMS applications in a standardized, rigorous, equitable and defensible manner. Methods: Our CaRMS applicant evaluation methods were first utilized in the 2017 CaRMS cycle, based on published Best Practices, and have been refined yearly to ensure validity, standardization, defensibility, rigour, and to improve the speed and flow of data processing. To determine the reliability of the total application scores for each rater, single measures intraclass correlation coefficients (ICCs) were calculated using a random effects model in 2017 and 2018. Curriculum, Tool or Material: A secure, online spreadsheet was created that includes applicant names, reviewer assignments, data entry boxes, and formulas. Each file reviewer entered data in a dedicated sheet within the document. Each application was reviewed by two staff physicians and two to four residents. File reviewers used a standardized, criterion-based scoring rubric for each application component. The file score for each reviewer-applicant pair was converted into a z-score based on each reviewer's distribution of scores. Z-scores of all reviewers for a single applicant were then combined by weighted average, with the group of staff and group of residents each being weighted to represent half of the final file score. The ICC for the total raw scores improved from 0.38 (poor) in 2017 to 0.52 (moderate) in 2018. The data from each reviewer was amalgamated into a master sheet where applicants were sorted by final file score and heat-mapped to offer a visual aid regarding differences in ratings. Conclusion: Our innovation uses heat-mapped and formula-populated spreadsheets, scoring rubrics, and z-scores to normalize variation in scoring trends between reviewers. We believe this approach provides a rigorous, defensible, and reproducible process by which Canadian residency programs can appraise applicants and create a rank order list.
To evaluate the impact of changes to urine testing orderables in computerized physician order entry (CPOE) system on urine culturing practices.
Retrospective before-and-after study.
A 1,250-bed academic tertiary-care referral center.
Hospitalized adults who had ≥1 urine culture performed during their stay.
The intervention (implemented in April 2017) consisted of notifications to providers, changes to order sets, and inclusion of the new urine culture reflex tests in commonly used order sets. We compared the urine culture rates before the intervention (January 2015 to April 2016) and after the intervention (May 2016 to August 2017), adjusting for temporal trends.
During the study period, 18,954 inpatients (median age, 62 years; 68.8% white and 52.3% female) had 24,569 urine cultures ordered. Overall, 6,662 urine cultures (27%) were positive. The urine culturing rate decreased significantly in the postintervention period for any specimen type (38.1 per 1,000 patient days preintervention vs 20.9 per 1,000 patient days postintervention; P < .001), clean catch (30.0 vs 18.7; P < .001) and catheterized urine (7.8 vs 1.9; P < .001). Using an interrupted time series model, urine culture rates decreased for all specimen types (P < .05).
Our intervention of changes to order sets and inclusion of the new urine culture reflex tests resulted in a 45% reduction in the urine cultures ordered. CPOE system format plays a vital role in reducing the burden of unnecessary urine cultures and should be implemented in combination with other efforts.
To evaluate the long-term safety and tolerability of deutetrabenazine in patients with tardive dyskinesia (TD) at 2years.
In the 12-week ARM-TD and AIM-TD studies, deutetrabenazine showed clinically significant improvements in Abnormal Involuntary Movement Scale scores compared with placebo, and there were low rates of overall adverse events (AEs) and discontinuations associated with deutetrabenazine.
Patients who completed ARM-TD or AIM-TD were included in this open-label, single-arm extension study, in which all patients restarted/started deutetrabenazine 12mg/day, titrating up to a maximum total daily dose of 48mg/day based on dyskinesia control and tolerability. The study comprised a 6-week titration period and a long-term maintenance phase. Safety measures included incidence of AEs, serious AEs (SAEs), and AEs leading to withdrawal, dose reduction, or dose suspension. Exposure-adjusted incidence rates (EAIRs; incidence/patient-years) were used to compare AE frequencies for long-term treatment with those for short-term treatment (ARM-TD and AIM-TD). This analysis reports results up to 2 years (Week106).
343 patients were enrolled (111 patients received placebo in the parent study and 232 received deutetrabenazine). There were 331.4 patient-years of exposure in this analysis. Through Week 106, EAIRs of AEs were comparable to or lower than those observed with short-term deutetrabenazine and placebo, including AEs of interest (akathisia/restlessness [long-term EAIR: 0.02; short-term EAIR range: 0–0.25], anxiety [0.09; 0.13–0.21], depression [0.09; 0.04–0.13], diarrhea [0.06; 0.06–0.34], parkinsonism [0.01; 0–0.08], somnolence/sedation [0.09; 0.06–0.81], and suicidality [0.02; 0–0.13]). The frequency of SAEs (EAIR 0.15) was similar to those observed with short-term placebo (0.33) and deutetrabenazine (range 0.06–0.33) treatment. AEs leading to withdrawal (0.08), dose reduction (0.17), and dose suspension (0.06) were uncommon.
These results confirm the safety outcomes seen in the ARM-TD and AIM-TD parent studies, demonstrating that deutetrabenazine is well tolerated for long-term use in TD patients.
Presented at: American Academy of Neurology Annual Meeting; April 21–27, 2018, Los Angeles, California,USA
Funding Acknowledgements: Funding: This study was supported by Teva Pharmaceuticals, Petach Tikva, Israel
To evaluate long-term efficacy of deutetrabenazine in patients with tardive dyskinesia (TD) by examining response rates from baseline in Abnormal Involuntary Movement Scale (AIMS) scores. Preliminary results of the responder analysis are reported in this analysis.
In the 12-week ARM-TD and AIM-TD studies, the odds of response to deutetrabenazine treatment were higher than the odds of response to placebo at all response levels, and there were low rates of overall adverse events and discontinuations associated with deutetrabenazine.
Patients with TD who completed ARM-TD or AIM-TD were included in this open-label, single-arm extension study, in which all patients restarted/started deutetrabenazine 12mg/day, titrating up to a maximum total daily dose of 48mg/day based on dyskinesia control and tolerability. The study comprised a 6-week titration and a long-term maintenance phase. The cumulative proportion of AIMS responders from baseline was assessed. Response was defined as a percent improvement from baseline for each patient from 10% to 90% in 10% increments. AlMS score was assessed by local site ratings for this analysis.
343 patients enrolled in the extension study (111 patients received placebo in the parent study and 232 patients received deutetrabenazine). At Week 54 (n=145; total daily dose [mean±standard error]: 38.1±0.9mg), 63% of patients receiving deutetrabenazine achieved ≥30% response, 48% of patients achieved ≥50% response, and 26% achieved ≥70% response. At Week 80 (n=66; total daily dose: 38.6±1.1mg), 76% of patients achieved ≥30% response, 59% of patients achieved ≥50% response, and 36% achieved ≥70% response. Treatment was generally well tolerated.
Patients who received long-term treatment with deutetrabenazine achieved response rates higher than those observed in positive short-term studies, indicating clinically meaningful long-term treatment benefit.
Presented at: American Academy of Neurology Annual Meeting; April 21–27, 2018, Los Angeles, California, USA.
Funding Acknowledgements: This study was supported by Teva Pharmaceuticals, Petach Tikva, Israel.
The role that vitamin D plays in pulmonary function remains uncertain. Epidemiological studies reported mixed findings for serum 25-hydroxyvitamin D (25(OH)D)–pulmonary function association. We conducted the largest cross-sectional meta-analysis of the 25(OH)D–pulmonary function association to date, based on nine European ancestry (EA) cohorts (n 22 838) and five African ancestry (AA) cohorts (n 4290) in the Cohorts for Heart and Aging Research in Genomic Epidemiology Consortium. Data were analysed using linear models by cohort and ancestry. Effect modification by smoking status (current/former/never) was tested. Results were combined using fixed-effects meta-analysis. Mean serum 25(OH)D was 68 (sd 29) nmol/l for EA and 49 (sd 21) nmol/l for AA. For each 1 nmol/l higher 25(OH)D, forced expiratory volume in the 1st second (FEV1) was higher by 1·1 ml in EA (95 % CI 0·9, 1·3; P<0·0001) and 1·8 ml (95 % CI 1·1, 2·5; P<0·0001) in AA (Prace difference=0·06), and forced vital capacity (FVC) was higher by 1·3 ml in EA (95 % CI 1·0, 1·6; P<0·0001) and 1·5 ml (95 % CI 0·8, 2·3; P=0·0001) in AA (Prace difference=0·56). Among EA, the 25(OH)D–FVC association was stronger in smokers: per 1 nmol/l higher 25(OH)D, FVC was higher by 1·7 ml (95 % CI 1·1, 2·3) for current smokers and 1·7 ml (95 % CI 1·2, 2·1) for former smokers, compared with 0·8 ml (95 % CI 0·4, 1·2) for never smokers. In summary, the 25(OH)D associations with FEV1 and FVC were positive in both ancestries. In EA, a stronger association was observed for smokers compared with never smokers, which supports the importance of vitamin D in vulnerable populations.
The dairy industry has continued to innovate to meet the needs of the consumers' specification of milk at a low price, of good hygienic quality and with rising expectations of animal welfare. The introduction of robotic milking offers the opportunity for the cost effective deployment of novel sensors for a variety of milk analytes. Traditional methods of monitoring health changes in animals are based entirely on the human senses. However, in modern milking systems humans rarely have enough time to see the cows to observe for signs of ill health, the extreme case is that of robotic milking. Novel sensors will allow closed loop control systems where the early detection of deviations from optimal performance will enable the farm manager to make management decisions before damage to potential milk yields is irreversible. Where a biological model already exists, for example, in the prediction of ovulation with milk progesterone analysis, rapid progress is being made towards an automated prediction system. Integrated management systems for dairy cows will not only have the traditional goals of efficient milk production but can also be tuned to reduce polluting outputs of ammonia, phosphorus and methane. The main metabolic markers in milk to be monitored are urea, fat, ketones and protein. The detection of mastitis can be achieved by the development of sensor systems to detect enzyme markers of inflammatory response such as Nagase. Multi-disciplinary research is needed to develop integrated management systems drawing all the different elements of dairy cow management into a single system. The major cause of death in dairy cows is dystocia and monitoring systems are needed to ensure that parturition is better managed.
This paper concentrates on livestock production systems by introducing sustainable housing characteristics, and the type of information required to make an informed choice on environmentally sound materials and systems. It then compares energy use in two contrasting beef cattle systems, one a conventional straw-bedded court and roofed silo, with feed delivered by a side-delivery wagon, and the other a roofless woodchip corral and earth-bank silo, with feed delivered by fore-end loader. The woodchip corral system requires 70% less energy than the conventional bedded court, when the total energy inputs are analysed for preparation of the building materials, construction of the livestock accommodation with associated feed and waste storage, and manufacture and operation of machinery. However, when energy used in feed production is included this dominates the energy budget, accounting for 60% of all energy used in the conventional bedded court, and 85% of energy used in the woodchip corral system.
A legionellosis outbreak at an industrial site was investigated to identify and control the source. Cases were identified from disease notifications, workplace illness records, and from clinicians. Cases were interviewed for symptoms and risk factors and tested for legionellosis. Implicated environmental sources were sampled and tested for legionella. We identified six cases with Legionnaires’ disease and seven with Pontiac fever; all had been exposed to aerosols from the cooling towers on the site. Nine cases had evidence of infection with either Legionella pneumophila serogroup (sg) 1 or Legionella longbeachae sg1; these organisms were also isolated from the cooling towers. There was 100% DNA sequence homology between cooling tower and clinical isolates of L. pneumophila sg1 using sequence-based typing analysis; no clinical L. longbeachae isolates were available to compare with environmental isolates. Routine monitoring of the towers prior to the outbreak failed to detect any legionella. Data from this outbreak indicate that L. pneumophila sg1 transmission occurred from the cooling towers; in addition, L. longbeachae transmission was suggested but remains unproven. L. longbeachae detection in cooling towers has not been previously reported in association with legionellosis outbreaks. Waterborne transmission should not be discounted in investigations for the source of L. longbeachae infection.
Cognitive reserve (CR) has been associated with better cognitive function and lower risk of depression in older people, yet it remains unclear whether CR moderates the association between mood and cognition. This study aimed to investigate whether a comprehensive indicator of CR, including education, occupation and engagement in cognitive and social activities, acts as a moderator of this association.
This was a cross-sectional study utilising baseline data from the Cognitive Function and Ageing Study II (CFAS II), a large population-based cohort of people aged 65+ in England. Complete data on the measures of CR, mood and cognition were available for 6565 dementia-free individuals. Linear regression models were used to investigate the potential modifying effect of CR on the association between cognition and mood with adjustment for age, sex and missing data.
Levels of CR did moderate the negative association between mood and cognition; the difference in cognition between those with and without a clinical level mood disorder was significantly smaller in the middle (−2.28; 95% confidence interval (CI) −3.65 to −0.90) and higher (−1.30; 95% CI −2.46 to −0.15) CR groups compared with the lower CR group (−4.01; 95% CI −5.53 to −2.49). The individual components of CR did not significantly moderate the negative association between mood and cognition.
These results demonstrate that CR, indexed by a composite score based on multiple indicators, can moderate the negative association between lowered mood and cognition, emphasising the importance of continuing to build CR across the lifespan in order to maintain cognitive health.
To prospectively assess treatment outcomes of chronic rhinosinusitis patients undergoing functional endoscopic sinus surgery and post-operative medical treatment over a prolonged follow-up period.
Patients undergoing functional endoscopic sinus surgery in the tertiary referral practice of a single surgeon were studied prospectively. Symptoms were scored by patients pre-operatively and over a minimum follow-up period of 12 months.
The study comprised 200 non-consecutive patients. The median pre-operative symptom score was 16 (out of a maximum of 25) (95 per cent confidence interval = 15 to 17). Symptom scores reduced to a median of 7 (95 per cent confidence interval = 6 to 8) after 12 months of follow up (p < 0.0001). The median symptom score improved for all symptoms and across all patient subgroups.
Extensive functional endoscopic sinus surgery offers significant and durable symptom improvement in patients with chronic rhinosinusitis refractory to medical treatment. This improvement extends to all patient subgroups. Prolonged medical therapy is recommended after functional endoscopic sinus surgery.
The Antarctic Roadmap Challenges (ARC) project identified critical requirements to deliver high priority Antarctic research in the 21st century. The ARC project addressed the challenges of enabling technologies, facilitating access, providing logistics and infrastructure, and capitalizing on international co-operation. Technological requirements include: i) innovative automated in situ observing systems, sensors and interoperable platforms (including power demands), ii) realistic and holistic numerical models, iii) enhanced remote sensing and sensors, iv) expanded sample collection and retrieval technologies, and v) greater cyber-infrastructure to process ‘big data’ collection, transmission and analyses while promoting data accessibility. These technologies must be widely available, performance and reliability must be improved and technologies used elsewhere must be applied to the Antarctic. Considerable Antarctic research is field-based, making access to vital geographical targets essential. Future research will require continent- and ocean-wide environmentally responsible access to coastal and interior Antarctica and the Southern Ocean. Year-round access is indispensable. The cost of future Antarctic science is great but there are opportunities for all to participate commensurate with national resources, expertise and interests. The scope of future Antarctic research will necessitate enhanced and inventive interdisciplinary and international collaborations. The full promise of Antarctic science will only be realized if nations act together.
Charcoal is the result of natural and anthropogenic burning events, when biomass is exposed to elevated temperatures under conditions of restricted oxygen. This process produces a range of materials, collectively known as pyrogenic carbon, the most inert fraction of which is known as black carbon (BC). BC degrades extremely slowly and is resistant to diagenetic alteration involving the addition of exogenous carbon, making it a useful target substance for radiocarbon dating particularly of more ancient samples, where contamination issues are critical. We present results of tests using a new method for the quantification and isolation of BC, known as hydropyrolysis (hypy). Results show controlled reductive removal of non-BC organic components in charcoal samples, including lignocellulosic and humic material. The process is reproducible and rapid, making hypy a promising new approach not only for isolation of purified BC for 14C measurement but also in quantification of different labile and resistant sample C fractions.
Salience network (SN) dysconnectivity has been hypothesized to contribute to schizophrenia. Nevertheless, little is known about the functional and structural dysconnectivity of SN in subjects at risk for psychosis. We hypothesized that SN functional and structural connectivity would be disrupted in subjects with At-Risk Mental State (ARMS) and would be associated with symptom severity and disease progression.
We examined 87 ARMS and 37 healthy participants using both resting-state functional magnetic resonance imaging and diffusion tensor imaging. Group differences in SN functional and structural connectivity were examined using a seed-based approach and tract-based spatial statistics. Subject-level functional connectivity measures and diffusion indices of disrupted regions were correlated with CAARMS scores and compared between ARMS with and without transition to psychosis.
ARMS subjects exhibited reduced functional connectivity between the left ventral anterior insula and other SN regions. Reduced fractional anisotropy (FA) and axial diffusivity were also found along white-matter tracts in close proximity to regions of disrupted functional connectivity, including frontal-striatal-thalamic circuits and the cingulum. FA measures extracted from these disrupted white-matter regions correlated with individual symptom severity in the ARMS group. Furthermore, functional connectivity between the bilateral insula and FA at the forceps minor were further reduced in subjects who transitioned to psychosis after 2 years.
Our findings support the insular dysconnectivity of the proximal SN hypothesis in the early stages of psychosis. Further developed, the combined structural and functional SN assays may inform the prognosis of persons at-risk for psychosis.
Not only is depression associated with increased inflammation but inflammation is a risk factor for the genesis of depression. Many of the environmental risk factors for depression are transduced through inflammatory signaling. Anti-inflammatory agents show promise for the management of depression in preclinical, epidemiological, and early clinical studies. This opens the door to the potential for anti-inflammatory agents to treat and prevent depression. There are no evidence-based pharmacotherapies for depression prevention.
ASPREE-D, aspirin in the prevention of depression in the elderly, is a sub study of ASPREE, which explores the potential of aspirin to prevent a range of inflammation related disorders in the elderly. With a sample size of 19,114, and a duration of 5 years, this placebo controlled study will be one of the largest randomized controlled trials in psychiatry and will provide definitive evidence on the ability of aspirin to prevent depression.
This paper presents the rationale for the study and presents a summary of the study design.
ASPREE-D may not only define novel therapy but will provide mechanistic proof of concept of the role of inflammation in depression.
In view of the considerable ground covered by the Commission at its Paris meetings and the fairly complete record of the activities of institutes and observatories, etc. published in the Minutes, it has not been deemed profitable by the president to call for further reports in advance of the Stockholm meeting. At the Paris meeting it was agreed that such reports be printed independently before each meeting of the Union and that reprints of or references to the published reports be sent to the president. It is hoped that all such reports if ready will be made available before the Stockholm meeting so that they may be summarized by the representatives in attendance or by the president and recorded in the Minutes. With reference to the pronouncement at the Paris meeting “that it is eminently desirable that more attention be given to the development of accurate general perturbations and mean elements on the basis of accurate osculating elements”, the president has visited the Planeten-Institut at Frankfurt and the Rechen-Institut at Berlin and has been in correspondence with the Leningrad Institute. From these sources particularly valuable material has been received.
We present the first results from multi-site observations of the δ Scuti star XX Pyx (CD–24°7599). The observations were carried out as the 17th run of the Delta Scuti Network. We collected 583 hr of B, V time-series photometry, resulting in a detection level (4σ) in the amplitude spectrum of 0.5 mmag. We detect 6 new pulsation frequencies, bringing the total number of frequencies known in this star up 19.
White dwarf stars provide important boundary conditions for the understanding of stellar evolution. An adequate understanding of even these simple stars is impossible without detailed knowledge of their interiors. PG1346+082, an interacting binary white dwarf system, provides a unique opportunity to view the interior of one degenerate as it is brought to light in the accretion disk of the second star as the primary strips material from its less massive companion (see Wood et at. 1987).
PG1346+082 is a photometric variable with a four magnitude variation over a four to five day quasi-period. A fast Fourier transform (FFT) of the light curve shows a complex, time-dependent structure of harmonics. PG1346+082 exhibits flickering – the signature of mass transfer. The optical spectra of the system contain weak emission features during minimum and broad absorption at all other times. This could be attributed to pressure broadening in the atmosphere of a compact object, or to a combination of pressure broadening and doppler broadening in a disk surrounding the compact accretor. No hydrogen lines are observed and the spectra are dominated by neutral helium. The spectra also display variable asymmetric line profiles.
The variability of CD-24 7599 (V=11.48 mag) was discovered by JCC during observing run XCOV7 of the Whole Earth Telescope (WET, Nather et al. 1990) network in February, 1992. The star was observed as an additional target and 117 hours of high-quality temporal spectroscopic observations were obtained.
Our analysis of these data revealed the presence of 7 independent pulsation modes between 27.0 and 38.1 cycles per day (313 – 441 μHz) with semiamplitudes of 2.1 – 10.2 milli-modulation amplitudes (mma). We showed that peaks at linear combination frequencies detected in the power spectra were not due to eigenmodes excited to visible amplitude by resonant mode coupling.