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.
We characterized the impact of removal of the ESBL designation from microbiology reports on inpatient antibiotic prescribing. Definitive prescribing of carbapenems decreased from 48.4% to 16.1% (P = .01) and β-lactam–β-lactamase inhibitor combination increased from 19.4% to 61.3% (P = .002). Our findings confirm the importance of collaboration between microbiology and antimicrobial stewardship programs.
The political underrepresentation of women and racial minorities in Canadian politics is well documented. One political arena that has yet to be examined in this respect, however, is school boards. Using data from a candidate survey conducted during the course of the 2018 Ontario school board elections, as well as demographic data collected on the entire population of school board candidates, we explore the unique characteristics of school board elections. The research note begins by describing the gender and racial composition of candidates and trustees in Canada's most populous province. It then considers the ways in which school board elections may serve as a launchpad to higher office for either of these two traditionally underrepresented groups, as we explore the features of progressive political ambition, recruitment into school board campaigns and the relative electoral success of racialized candidates and women in this local office. While women do very well in school board elections, they are significantly less likely than their male counterparts to have the desire to move up to provincial or federal politics. Meanwhile, racialized candidates contest school board election in significant numbers and report similar levels of progressive ambition relative to their white counterparts, but they fare exceptionally poorly in school board elections.
Chronic non-cancer pain (CNCP) involves one-third of the US population, and prescription opioids contribute to the opioid epidemic. The Centers for Disease Control and Prevention emphasizes maximizing non-opioid treatment, but many rural populations cannot access alternative therapies. Clinical and Translational Science Award hubs across four rural states performed a multi-site, single-arm intervention feasibility study testing methods and procedures of implementing a behavioral intervention, acceptance and commitment therapy, in primary care CNCP patients on chronic opioids. Using the CONSORT extension for feasibility studies, we describe lessons learned in recruiting/retaining participants, intervention implementation, data measurement, and multi-site procedures. Results inform a future definitive trial and potentially others conducting rural trials.
To evaluate the National Health Safety Network (NHSN) hospital-onset Clostridioides difficile infection (HO-CDI) standardized infection ratio (SIR) risk adjustment for general acute-care hospitals with large numbers of intensive care unit (ICU), oncology unit, and hematopoietic cell transplant (HCT) patients.
Retrospective cohort study.
Eight tertiary-care referral general hospitals in California.
We used FY 2016 data and the published 2015 rebaseline NHSN HO-CDI SIR. We compared facility-wide inpatient HO-CDI events and SIRs, with and without ICU data, oncology and/or HCT unit data, and ICU bed adjustment.
For these hospitals, the median unmodified HO-CDI SIR was 1.24 (interquartile range [IQR], 1.15–1.34); 7 hospitals qualified for the highest ICU bed adjustment; 1 hospital received the second highest ICU bed adjustment; and all had oncology-HCT units with no additional adjustment per the NHSN. Removal of ICU data and the ICU bed adjustment decreased HO-CDI events (median, −25%; IQR, −20% to −29%) but increased the SIR at all hospitals (median, 104%; IQR, 90%–105%). Removal of oncology-HCT unit data decreased HO-CDI events (median, −15%; IQR, −14% to −21%) and decreased the SIR at all hospitals (median, −8%; IQR, −4% to −11%).
For tertiary-care referral hospitals with specialized ICUs and a large number of ICU beds, the ICU bed adjustor functions as a global adjustment in the SIR calculation, accounting for the increased complexity of patients in ICUs and non-ICUs at these facilities. However, the SIR decrease with removal of oncology and HCT unit data, even with the ICU bed adjustment, suggests that an additional adjustment should be considered for oncology and HCT units within general hospitals, perhaps similar to what is done for ICU beds in the current SIR.
Forty years ago, Knut Fladmark (1979) argued that the Pacific Coast offered a viable alternative to the ice-free corridor model for the initial peopling of the Americas—one of the first to support a “coastal migration theory” that remained marginal for decades. Today, the pre-Clovis occupation at the Monte Verde site is widely accepted, several other pre-Clovis sites are well documented, investigations of terminal Pleistocene subaerial and submerged Pacific Coast landscapes have increased, and multiple lines of evidence are helping decode the nature of early human dispersals into the Americas. Misconceptions remain, however, about the state of knowledge, productivity, and deglaciation chronology of Pleistocene coastlines and possible technological connections around the Pacific Rim. We review current evidence for several significant clusters of early Pacific Coast archaeological sites in North and South America that include sites as old or older than Clovis. We argue that stemmed points, foliate points, and crescents (lunates) found around the Pacific Rim may corroborate genomic studies that support an early Pacific Coast dispersal route into the Americas. Still, much remains to be learned about the Pleistocene colonization of the Americas, and multiple working hypotheses are warranted.
This trial compared weight loss outcomes over 14 weeks in women showing low- or high-satiety responsiveness (low- or high-satiety phenotype (LSP, HSP)) measured by a standardised protocol. Food preferences and energy intake (EI) after low and high energy-density (LED, HED) meals were also assessed. Ninety-six women (n 52 analysed; 41·24 (SD 12·54) years; 34·02 (sd 3·58) kg/m2) engaged in one of two weight loss programmes underwent LED and HED laboratory test days during weeks 3 and 12. Preferences for LED and HED food (Leeds Food Preference Questionnaire) and ad libitum evening meal and snack EI were assessed in response to equienergetic LED and HED breakfasts and lunches. Weekly questionnaires assessed control over eating and ease of adherence to the programme. Satiety quotients based on subjective fullness ratings post LED and HED breakfasts determined LSP (n 26) and HSP (n 26) by tertile splits. Results showed that the LSP lost less weight and had smaller reductions in waist circumference compared with HSP. The LSP showed greater preferences for HED foods, and under HED conditions, consumed more snacks (kJ) compared with HSP. Snack EI did not differ under LED conditions. LSP reported less control over eating and reported more difficulty with programme adherence. In conclusion, low-satiety responsiveness is detrimental for weight loss. LED meals can improve self-regulation of EI in the LSP, which may be beneficial for longer-term weight control.
Background: Focal cortical dysplasias (FCDs) are congenital structural abnormalities of the brain, and represent the most common cause of medication-resistant focal epilepsy in children and adults. Recent studies have shown that somatic mutations (i.e. mutations arising in the embryo) in mTOR pathway genes underlie some FCD cases. Specific therapies targeting the mTOR pathway are available. However, testing for somatic mTOR pathway mutations in FCD tissue is not performed on a clinical basis, and the contribution of such mutations to the pathogenesis of FCD remains unknown. Aim: To investigate the feasibility of screening for somatic mutations in resected FCD tissue and determine the proportion and spatial distribution of FCDs which are due to low-level somatic mTOR pathway mutations. Methods: We performed ultra-deep sequencing of 13 mTOR pathway genes using a custom HaloPlexHS target enrichment kit (Agilent Technologies) in 16 resected histologically-confirmed FCD specimens. Results: We identified causal variants in 62.5% (10/16) of patients at an alternate allele frequency of 0.75–33.7%. The spatial mutation frequency correlated with the FCD lesion’s size and severity. Conclusions: Screening FCD tissue using a custom panel results in a high yield, and should be considered clinically given the important potential implications regarding surgical resection, medical management and genetic counselling.
Oceanic anoxic events (OAEs) are contemporaneous with 11 of the 18 largest Phanerozoic extinction events, but the magnitude and selectivity of their paleoecological impact remains disputed. OAEs are associated with abrupt, rapid warming and increased CO2 flux to the atmosphere; thus, insights from this study may clarify the impact of current anthropogenic climate change on the biosphere. We investigated the influence of the Late Cretaceous Bonarelli event (OAE2; Cenomanian/Turonian stage boundary; ~94 Ma) on generic- and species-level molluscan diversity, extinction rates, and ecological turnover. Cenomanian/Turonian results were compared with changes across all Cretaceous stage boundaries, some of which are coincident with less severe OAEs. We found increased generic turnover, but not species-level turnover, associated with several Cretaceous OAEs. The absence of a species-level pattern may reflect species occurrence data that are too temporally coarse to robustly detect patterns. Five hypotheses of ecological selectivity relating anoxia to survivorship were tested across stage boundaries with respect to faunality, mobility, and diet using generalized linear models. Interestingly, benthic taxa were consistently selected against throughout the Cretaceous regardless of the presence or absence of OAEs. These results suggest that: (1) the Cenomanian/Turonian boundary (OAE2) was associated with a decline in molluscan diversity and increase in extinction rate that were significantly more severe than Cretaceous background levels; and (2) no differential ecological selectivity was associated with OAE-related diversity declines among the variables tested here.
We assessed whether paternal demographic, anthropometric and clinical factors influence the risk of an infant being born large-for-gestational-age (LGA). We examined the data on 3659 fathers of term offspring (including 662 LGA infants) born to primiparous women from Screening for Pregnancy Endpoints (SCOPE). LGA was defined as birth weight >90th centile as per INTERGROWTH 21st standards, with reference group being infants ⩽90th centile. Associations between paternal factors and likelihood of an LGA infant were examined using univariable and multivariable models. Men who fathered LGA babies were 180 g heavier at birth (P<0.001) and were more likely to have been born macrosomic (P<0.001) than those whose infants were not LGA. Fathers of LGA infants were 2.1 cm taller (P<0.001), 2.8 kg heavier (P<0.001) and had similar body mass index (BMI). In multivariable models, increasing paternal birth weight and height were independently associated with greater odds of having an LGA infant, irrespective of maternal factors. One unit increase in paternal BMI was associated with 2.9% greater odds of having an LGA boy but not girl; however, this association disappeared after adjustment for maternal BMI. There were no associations between paternal demographic factors or clinical history and infant LGA. In conclusion, fathers who were heavier at birth and were taller were more likely to have an LGA infant, but maternal BMI had a dominant influence on LGA.
Background: Methionyl-tRNA synthetase (MARS) links methionine to its cognate tRNA required for translation. MARS mutations have been linked to adult-onset CMT2U. Methods: The proband had weakness in her first year of life, sitting at 11 months and walking at 20 months old. At 4 years old she was areflexic with distal > proximal weakness. Nerve conduction studies showed normal median and sural sensory responses with absent common peroneal, low median and tibial motor amplitudes. EMG noted denervation and quadriceps biopsy revealed neurogenic atrophy. Genetic testing for spinal muscular atrophy and sequencing of MNF2, RAB7A, LMNA, MPZ, HSPB1, NEFL, GADP1, TRPV4, HSPB8, GJB1 and PLEK8G5 were negative. She stopped walking at 9 years old and could not raise her arms above her head at 11 years old. Results: Exome sequencing identified MARS: c.1189G>A; p.Ala397Thr. To determine the functional consequences of p.A397T-MARS, yeast complementation assays were performed. Wild type or mutant MARS were cloned into yeast lacking the endogenous MARS ortholog. Wild-type MARS supported robust cellular growth, while the p.A397T-MARS insert did not support cellular growth confirming deleterious effect of this variant. Conclusions: Our patient’s phenotype was similar to children with motor-predominant GARS mutations. Functional data notes this MARS variant to be damaging and predictive of a severe, early-onset phenotype.
OBJECTIVES/SPECIFIC AIMS: Emotional processing theory and some observations suggest that activation of subjective and physiological distress during therapeutic exposure and habituation across exposure sessions are key to improvement. This study sought to determine whether initial subjective and physiological activation and between-session habituation would predict PTSD symptom reduction after a series of written trauma narrative exposure sessions. METHODS/STUDY POPULATION: In total, 29 urban-residing African-American participants with PTSD participated in four 30-minute writing sessions. Writing sessions 1 and 2 were 12 hours apart and session 3 and 4 were performed 1 week later, also 12 hours apart. PTSD symptoms were measured at baseline, after session 2, and 1 week after all 4 writing sessions with the Clinician Administered PTSD Scale. During each session, Subjective Units of Distress Scores (SUDS) were assessed 4 times and heart rate was measured continuously. RESULTS/ANTICIPATED RESULTS: Participants exhibited PTSD symptom improvement and habituation of subjective distress, but not physiological arousal, across writing sessions. First session baseline-corrected SUDS maximum and SUDS decrease from the initial to the final writing session were both positively associated with symptom improvement. DISCUSSION/SIGNIFICANCE OF IMPACT: Increased subjective, but not physiological, distress in the first exposure session and diminished subjective distress across sessions may be a helpful marker of emotional processing for clinicians and predictor of symptom improvement after written trauma narrative exposure.
Hemorrhage remains the major cause of preventable death after trauma. Recent data suggest that earlier blood product administration may improve outcomes. The purpose of this study was to determine whether opportunities exist for blood product transfusion by ground Emergency Medical Services (EMS).
This was a single EMS agency retrospective study of ground and helicopter responses from January 1, 2011 through December 31, 2015 for adult trauma patients transported from the scene of injury who met predetermined hemodynamic (HD) parameters for potential transfusion (heart rate [HR]≥120 and/or systolic blood pressure [SBP]≤90).
A total of 7,900 scene trauma ground transports occurred during the study period. Of 420 patients meeting HD criteria for transfusion, 53 (12.6%) had a significant mechanism of injury (MOI). Outcome data were available for 51 patients; 17 received blood products during their emergency department (ED) resuscitation. The percentage of patients receiving blood products based upon HD criteria ranged from 1.0% (HR) to 5.9% (SBP) to 38.1% (HR+SBP). In all, 74 Helicopter EMS (HEMS) transports met HD criteria for blood transfusion, of which, 28 patients received prehospital blood transfusion. Statistically significant total patient care time differences were noted for both the HR and the SBP cohorts, with HEMS having longer time intervals; no statistically significant difference in mean total patient care time was noted in the HR+SBP cohort.
In this study population, HD parameters alone did not predict need for ED blood product administration. Despite longer transport times, only one-third of HEMS patients meeting HD criteria for blood administration received prehospital transfusion. While one-third of ground Advanced Life Support (ALS) transport patients manifesting HD compromise received blood products in the ED, this represented 0.2% of total trauma transports over the study period. Given complex logistical issues involved in prehospital blood product administration, opportunities for ground administration appear limited within the described system.
MixFM, ZielinskiMD, MyersLA, BernsKS, LukeA, StubbsJR, ZietlowSP, JenkinsDH, SztajnkrycerMD. Prehospital Blood Product Administration Opportunities in Ground Transport ALS EMS – A Descriptive Study. Prehosp Disaster Med. 2018;33(3):230–236.
The use of monthly intranasal mupirocin was associated with a significant reduction in the rate of methicillin-resistant Staphylococcus aureus transmission and Staphylococcus aureus invasive infection in a large neonatal intensive care unit. Resistance to mupirocin emerged over time, but it was rare and was not associated with adverse clinical outcomes.
The Joint Commission Centre for Transforming Healthcare's Web-based Targeted Solutions Tool (TST) for improving hand hygiene was implemented to elucidate contributing factors to low compliance rates of hand hygiene. Monitoring of compliance was done by trained unknown and known observers and rates of hospital-acquired infections were tracked and correlated against the changes in hand hygiene compliance. In total, 5669 of hand hygiene observations were recorded by the secret observers. The compliance rate increased from 75·4% at baseline (May–August 2014) to 88·6% during the intervention (13 months) and the control periods (P < 0·0001). Reductions in healthcare-associated infection rates were recorded for Clostridium difficle infections from 7·95 (CI 0·8937–28·72) to 1·84 (CI 0·02411–10·26) infections per 10 000 patient-days (P = 0·23), central line-associated blood-stream infections from 5·9 (CI 1·194–17·36) to 2·9 (0·7856–7·475) per 1000 device days (P = 0·37) and catheter-associated urinary tract infections from 5·941 (CI 1·194–17·36) to 0 per 1000 device days (P = 0·42). The top contributing factors for non-compliance were: improper use of gloves, hands full of supplies or medications and frequent entry or exit in isolation areas. We conclude that the application of TST allows healthcare organisations to improve hand hygiene compliance and to identify the factors contributing to non-compliance.