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To compare the effects of empiric carbapenems versus cycling cefepime and piperacillin/tazobactam on the rates of vancomycin-resistant Enterococcus (VRE) colonization, bloodstream infections, and outcomes of patients admitted with acute leukemia.
Retrospective clinical study with VRE molecular strain typing and gastrointestinal microbiome comparison.
A regional referral center for acute leukemia.
342 consecutive patients admitted with newly diagnosed acute leukemia.
In September 2015, we changed our empiric antibiotic of choice for neutropenic fever from a carbapenem to the cycling regimen. We studied 214 consecutive patients during the carbapenem period and 128 during the cycling period. Surveillance for VRE stool colonization was conducted weekly. Representative stool samples were analyzed for VRE MLST types and changes in the composition and diversity of the fecal microbiota.
The change in empiric antibiotics was associated with a significant decrease in VRE colonization (hazard ratio [HR], 0.35; 95% confidence interval [CI], 0.27–0.66), a switch in the dominant VRE MLST types on the unit, and some modifications in the gastrointestinal microbiome. There were no differences in total gram-positive or gram-negative BSIs. During the carbapenem period, we observed higher absolute numbers of Candida spp and fewer ESBL BSIs, but these did not reach statistical significance. Patients during the carbapenem period had longer lengths of stay and durations of severe neutropenia and 10% higher hospital cost.
Carbapenem-sparing empiric antibiotic regimens may have advantages related to VRE ecology, gastrointestinal dysbiosis, duration of neutropenia, cost and length of stay.
Tear staining (TS) in the pig has been related to different stressors and may be a useful tool for assessing animal welfare on farm. The aim of the current study was to investigate TS across the finisher period and its possible relation to age, growth, sex and experimentally induced stressors. The study included 80 finisher pens divided between three batches. Within each batch, the pens either included pigs with docked or undocked tails, had straw provided (150 g/pig/day) or not and had a low (1.21 m2/pig, 11 pigs) or high stocking density (0.73 m2/pig, 18 pigs). Tear staining (scores 1 to 4; from smaller to larger tear stain area, respectively) and tail damage were scored on each individual pig three times per week over the 9-week study period, and the individual maximum TS score within each week was chosen for further analysis. Data were analysed using logistic regression separately for each of the four possible TS score levels. The TS scores 1 and 2 decreased with weeks into the study period and were negatively related to the average daily gain (ADG) of the pigs, whereas the TS score 4 increased with weeks into the study period and was positively related to ADG. None of the TS scores differed between females and castrated males, and neither straw provision nor lowering the stocking density affected the TS scores. However, the TS score 1 decreased the last week before an event of tail damage (at least one pig in the pen with a bleeding tail wound), whereas the TS score 4 increased. The results of the current study advocates for a relation between TS and the factors such as age, growth and stress in the pig, while no relation was found between TS and the environmental factors straw provision and lowered stocking density. The relations to age and growth are important to take into consideration if using TS as a welfare assessment measure in the pig in the future.
Loose farrowing pens have been considered as alternatives to crates to enhance sow welfare. A major concern with pen systems is often higher piglet pre-weaning mortality, especially due to crushing by the sow. An optimal management of light and mat surface temperature may promote greater piglet use of the creep, which has been associated with reduced piglet crushing. A total of 108 sows and their piglets were studied in sow welfare and piglet protection pens on a commercial piggery, across two replicates. Sows were randomly assigned to pens arranged within two creep treatments (bright creep: 300 lx v. dark creep: 4 lx), considering mat temperature as a covariate. Twelve sows and their litters in each treatment (24 in total) had their behaviour continuously recorded for 72-h postpartum (pp), and four focal piglets per litter were weighed on the first and third days pp. In situ behaviour observations were performed daily (from 0800 to 1700 h) on all sows and their litters, every 15 min over 72-h pp to record piglet time spent in the creep, latency to enter the creep for the first time, latency for the litter to remain in the creep for at least 10 min, and piglet and sow use of pen areas immediately in front of (A2) and farthest from the creep (A3). Piglets with access to bright creeps spent on average 7.2% more time (P<0.01) in the creeps than piglets in pens with Dark creeps. In addition, for each degree increase in mat temperature, piglets spent on average 2.1% more time (P<0.01) in the creep. Piglets in pens with bright creeps spent less time in A2 (P=0.04) and the least time in A3 (P=0.01). Light or mat temperature did not affect sow use of pen areas or piglet weight gain. Piglets with bright creeps tended (P=0.06) to take longer to enter the creep for the first time after birth, but the latency for 30.0% of the litter to remain clustered for 10 min tended (P=0.08) to be shorter in bright compared to dark creeps. Overall, piglet use of the creep increased with warm mat temperatures and brightness, which should be further investigated as potential strategies to promote piglet safety and reduce crushing in pen farrowing systems.
Landraces (including heritage varieties) are an important agrobiodiversity resource offering considerable value as a buffer against crop failures, as a crop for niche markets, and as a source of diversity for crop genetic improvement activities underpinning future food security. Home gardens are reservoirs of landrace diversity, but some of the accessions held in them are vulnerable or threatened with extinction. Those associated with seed saving networks have added security, for example, ca. 800 varieties are stored in the Heritage Seed Library (HSL) of Garden Organic, UK. In this study, Amplified Fragment Length Polymorphisms-based genetic analysis of accessions held in the HSL was used to (a) demonstrate the range of diversity in the collection, (b) characterize accessions to aid collection management and (c) promote broader use of the collection. In total, 171 accessions were included from six crops: Vicia faba L., Pisum sativum L., Daucus carota L., Cucumis sativus L., Lactuca sativa L. and Brassica oleracea L. var. acephala (DC.) Metzq. Average expected heterozygosity ranged from 0.18 to 0.28 in D. carota; 0.02–0.18 in P. sativum; 0.05–0.18 in L. sativa; 0.15–0.26 in B. oleracea var. acephala; 0.15–0.37 in C. sativus and 0.07–0.36 in V. faba. Genetic diversity and Fst values generally reflected the breeding system and cultivation history of the different crops. Comparisons of the diversity found in heritage varieties with that found in commercial varieties did not show a consistent pattern. Principal coordinates analysis and Unweighted Pair Group Method with Arithmetic Mean cluster analysis were used to identify four potential duplicate accession pairs.
During vocalization, efference copy/corollary discharge mechanisms suppress the auditory cortical response to self-generated sounds. Previously, we found attenuated vocalization-related auditory cortical suppression in psychosis and a similar trend in the psychosis risk syndrome. Here, we report data from the final sample of early illness schizophrenia patients (ESZ), individuals at clinical high risk for psychosis (CHR), and healthy controls (HC).
Event-related potentials (ERP) were recorded from ESZ (n = 84), CHR (n = 71), and HC (n = 103) participants during a vocalization paradigm. The N1 ERP component was elicited during production (Talk) and playback (Listen) of vocalization. Age effects on N1 suppression (Talk–Listen), Talk N1, and Listen N1 were compared across groups. N1 measures were adjusted for normal aging before testing for group differences.
Both ESZ and CHR groups showed reduced Talk–Listen N1 suppression relative to HC, but did not differ from each other. Listen N1 was reduced in ESZ, but not in CHR, relative to HC. Deficient Talk–Listen N1 suppression was associated with greater unusual thought content in CHR individuals. N1 suppression increased with age in HC (12–36 years), and while CHR individuals showed a similar age-related increase, no such relationship was evident in ESZ.
Putative efference copy/corollary discharge-mediated auditory cortical suppression during vocalization is deficient in ESZ and precedes psychosis onset, particularly in CHR individuals with greater unusual thought content. Furthermore, this suppression increases from adolescence through early adulthood, likely reflecting the effects of normal brain maturation. This maturation effect is disrupted in ESZ, presumably due to countervailing illness effects.
Trans-10, cis-12-conjugated linoleic acid (CLA) is a potent bioactive fatty acids (FA) that causes milk fat depression in lactating animals. FA are transferred to milk directly through chylomicrons and indirectly by recycling through other tissues. The objective of this study was to characterise the kinetics of trans-10, cis-12 CLA transfer to plasma and milk after a single bolus infusion. Five multiparous mid-lactation cows received a single abomasal bolus infusion of an enriched CLA mixture providing 15 g of trans-10, cis-12 CLA and 15 g of cis-9, trans-11 CLA over a 30-min period. Plasma concentration of trans-10, cis-12 and cis-9, trans-11 CLA peaked 2 h post-bolus, reaching 0·29 and 0·38 % of total plasma FA, respectively, and returned to pre-bolus values at 72 h post-infusion. Milk trans-10, cis-12 CLA yield and concentration peaked 14 h post-bolus (0·25 g/h) and was not detectable in milk after 86 h. Total apparent transfer of trans-10, cis-12 CLA to milk was 41 %, with 73 % transferred to milk through the direct pool (chylomicrons) and the remaining 27 % transferred through the indirect pool (tissue recycling). Compartmental modelling revealed the existence of a transient unavailable pool of trans-10, cis-12 CLA in extravascular tissues represented primarily by the mammary gland, which slowly exchanges with an available pool for secretion in milk fat and transfer to milk. In conclusion, trans-10, cis-12 CLA is predominantly transferred to milk through the direct pathway; however, how this CLA isomer is processed within the mammary gland requires further investigation.
Group housing of gestating sows benefits their welfare by allowing them freedom of movement and the opportunity for social interaction. However, social life could also bring disadvantages for individuals who receive direct aggression or are displaced from the feeder. The aim of this study was to investigate associations between social behaviour, body condition and live weight. Gestating sows (n=298) were investigated on a commercial farm. Sows were housed in mixed parity groups where two single space, ad libitum trough feeders served 12 animals. Sows were weighed, body condition scored and had their back fat layer measured at mixing, 4 weeks after insemination and again before farrowing. Social status was estimated based on the numbers of won and lost agonistic interactions at mixing and at the end of gestation. In addition, tear staining was scored before the farrowing and reproductive performance data were collected. With the aid of video recordings, 100 to 150 interactions per group were observed. Winning percentage at mixing and at the end of gestation were associated (P<0.05) and appeared relatively stable within individuals. Tear staining scores and litter sizes were not associated with winning percentage at the end of gestation. However, live weight, relative weight, body condition and back fat thickness were associated with winning percentage (P<0.05), giving heavier animals an advantage. Low winning percentage related to lower live weight gain, probably due to poorer success in competition for feed. Live weight within a mixed parity group could be used as a proxy measure for social status. Sows with low body condition score and submissive sows might need special attention with regard to group dynamics and housing to alleviate the effects of competition in group housing.
We aimed to explore multiple perspectives regarding barriers to and facilitators of advance care planning (ACP) among African Americans to identify similarities or differences that might have clinical implications.
Qualitative study with health disparities experts (n = 5), community members (n = 9), and seriously ill African American patients and caregivers (n = 11). Using template analysis, interviews were coded to identify intrapersonal, interpersonal, and systems-level themes in accordance with a social ecological framework.
Participants identified seven primary factors that influence ACP for African Americans: religion and spirituality; trust and mistrust; family relationships and experiences; patient-clinician relationships; prognostic communication, care preferences, and preparation and control. These influences echo those described in the existing literature; however, our data highlight consistent differences by group in the degree to which these factors positively or negatively affect ACP. Expert participants reinforced common themes from the literature, for example, that African Americans were not interested in prognostic information because of mistrust and religion. Seriously ill patients were more likely to express trust in their clinicians and to desire prognostic communication; they and community members expressed a desire to prepare for and control the end of life. Religious belief did not appear to negate these desires.
Significance of results
The literature on ACP in African Americans may not accurately reflect the experience of seriously ill African Americans. What are commonly understood as barriers to ACP may in fact not be. We propose reframing stereotypical barriers to ACP, such as religion and spirituality, or family, as cultural assets that should be engaged to enhance ACP. Although further research can inform best practices for engaging African American patients in ACP, findings suggest that respectful, rapport-building communication may facilitate ACP. Clinicians are encouraged to engage in early ACP using respectful and rapport building communication practices, including open-ended questions.
Reducing sugar-sweetened beverage consumption is a public health priority, yet finding an effective and acceptable policy intervention is challenging. One strategy is to use proportional pricing (a consistent price per fluid ounce) instead of the typical value-priced approach where large beverages offer better value. The purpose of the present study was to evaluate whether proportional pricing affects the purchasing of fountain beverages at a university cinema concession stand.
Four price strategies for beverages were evaluated over ten weekends of film screenings. We manipulated two factors: the price structure (value pricing v. proportional pricing) and the provision of information about the price per fluid ounce (labels v. no labels). The key outcomes were the number and size of beverages purchased. We analysed data using regression analyses, with standard errors clustered by film and controlling for the day and time of purchase.
A university cinema concession stand in Minnesota, USA, in spring 2015.
Over the study period (360 beverages purchased) there were no significant effects of the proportional pricing treatment. Pairing a label with the standard value pricing increased the likelihood of purchasing large drinks but the label did not affect purchasing when paired with proportional pricing.
Proportional prices did not significantly affect the size of beverages purchased by students at a university cinema, but adding a price-per-ounce label increased large drink purchases when drinks were value-priced. More work is needed to address whether pricing and labelling strategies might promote healthier beverage purchases.
To quantifying the interdependency within the regulatory environment governing human subject research, including Institutional Review Boards (IRBs), federally mandated Medicare coverage analysis and contract negotiations.
Over 8000 IRB, coverage analysis and contract applications initiated between 2013 and 2016 were analyzed using traditional and machine learning analytics for a quality improvement effort to improve the time required to authorize the start of human research studies.
Staffing ratios, study characteristics such as the number of arms, source of funding and number and type of ancillary reviews significantly influenced the timelines. Using key variables, a predictive algorithm identified outliers for a workflow distinct from the standard process. Improved communication between regulatory units, integration of common functions, and education outreach improved the regulatory approval process.
Understanding and improving the interdependencies between IRB, coverage analysis and contract negotiation offices requires a systems approach and might benefit from predictive analytics.
Recent research has identified several potentially modifiable risk factors for dementia, including mental disorders. Psychotic disorders, such as schizophrenia and delusional disorder, have also been associated with increased risk of cognitive impairment and dementia, but currently available data difficult to generalise because of bias and confounding. We designed the present study to investigate if the presence of a psychotic disorder increased the risk of incident dementia in later life.
Prospective cohort study of a community-representative sample of 37 770 men aged 65–85 years who were free of dementia at study entry. They were followed for up to 17.7 years using electronic health records. Clinical diagnoses followed the International Classification of Diseases guidelines. As psychotic disorders increase mortality, we considered death a competing risk.
A total of 8068 (21.4%) men developed dementia and 23 999 (63.5%) died during follow up. The sub-hazard ratio of dementia associated with a psychotic disorder was 2.67 (95% CI 2.30–3.09), after statistical adjustments for age and prevalent cardiovascular, respiratory, gastrointestinal and renal diseases, cancer, as well as hearing loss, depressive and bipolar disorders, and alcohol use disorder. The association between psychotic disorder and dementia risk varied slightly according to the duration of the psychotic disorder (highest for those with the shortest illness duration), but not the age of onset. No information about the use of antipsychotics was available.
Older men with a psychotic disorder have nearly three times greater risk of developing dementia than those without psychosis. The pathways linking psychotic disorders to dementia remain unclear but may involve mechanisms other than those associated with Alzheimer's disease and other common dementia syndromes.
Schizophrenia (SZ) is a severe neuropsychiatric disorder associated with disrupted connectivity within the thalamic-cortico-cerebellar network. Resting-state functional connectivity studies have reported thalamic hypoconnectivity with the cerebellum and prefrontal cortex as well as thalamic hyperconnectivity with sensory cortical regions in SZ patients compared with healthy comparison participants (HCs). However, fundamental questions remain regarding the clinical significance of these connectivity abnormalities.
Resting state seed-based functional connectivity was used to investigate thalamus to whole brain connectivity using multi-site data including 183 SZ patients and 178 matched HCs. Statistical significance was based on a voxel-level FWE-corrected height threshold of p < 0.001. The relationships between positive and negative symptoms of SZ and regions of the brain demonstrating group differences in thalamic connectivity were examined.
HC and SZ participants both demonstrated widespread positive connectivity between the thalamus and cortical regions. Compared with HCs, SZ patients had reduced thalamic connectivity with bilateral cerebellum and anterior cingulate cortex. In contrast, SZ patients had greater thalamic connectivity with multiple sensory-motor regions, including bilateral pre- and post-central gyrus, middle/inferior occipital gyrus, and middle/superior temporal gyrus. Thalamus to middle temporal gyrus connectivity was positively correlated with hallucinations and delusions, while thalamus to cerebellar connectivity was negatively correlated with delusions and bizarre behavior.
Thalamic hyperconnectivity with sensory regions and hypoconnectivity with cerebellar regions in combination with their relationship to clinical features of SZ suggest that thalamic dysconnectivity may be a core neurobiological feature of SZ that underpins positive symptoms.
Most indoor sows in Denmark and the UK continue to farrow in crates. Before farrowing, sows are highly motivated to nest-build and gilts farrowing in crates without straw have an especially large stress response over the nest-building period (Jarvis et al., 1997). In non-crated sows, the inability to nest-build affects the subsequent maternal behaviour of the sow after farrowing (Herskin et al., 1999). This study aimed to determine whether supplying straw before farrowing increased the anti-crushing and anti-predator behaviour of the crated sow after farrowing and improved piglet survival.
Current commercial dairy practice involves the removal of the calf from the dam within the first two days of life. This early separation may result in stress for both cow and calf. However, it may also be that separation occurs before the cow-calf bond is established. The aim of this study was to determine if cows and calves respond to each other's calls after separation and whether they could distinguish their own calf's or dam's calls from another calf's or cow's calls.
The ‘standard’ human approach test has been used extensively since the early 1980's to assess fear responses in most farmed species. However, in recent years, there has been considerable debate questioning its efficacy given the short duration of the familiarisation period and the suitability of the location of the testing environment, i.e. the home pen versus a novel arena (Pedersen, 1997). It is possible that the test simply reflects an animal's level of motivation to explore the novel arena and any novel objects therein rather than a specific response to the presence of a human. This work addresses both the length of acclimatisation period and the location of the test arena.