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The majority of paediatric Clostridioides difficile infections (CDI) are community-associated (CA), but few data exist regarding associated risk factors. We conducted a case–control study to evaluate CA-CDI risk factors in young children. Participants were enrolled from eight US sites during October 2014–February 2016. Case-patients were defined as children aged 1–5 years with a positive C. difficile specimen collected as an outpatient or ⩽3 days of hospital admission, who had no healthcare facility admission in the prior 12 weeks and no history of CDI. Each case-patient was matched to one control. Caregivers were interviewed regarding relevant exposures. Multivariable conditional logistic regression was performed. Of 68 pairs, 44.1% were female. More case-patients than controls had a comorbidity (33.3% vs. 12.1%; P = 0.01); recent higher-risk outpatient exposures (34.9% vs. 17.7%; P = 0.03); recent antibiotic use (54.4% vs. 19.4%; P < 0.0001); or recent exposure to a household member with diarrhoea (41.3% vs. 21.5%; P = 0.04). In multivariable analysis, antibiotic exposure in the preceding 12 weeks was significantly associated with CA-CDI (adjusted matched odds ratio, 6.25; 95% CI 2.18–17.96). Improved antibiotic prescribing might reduce CA-CDI in this population. Further evaluation of the potential role of outpatient healthcare and household exposures in C. difficile transmission is needed.
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 development of laser wakefield accelerators (LWFA) over the past several years has led to an interest in very compact sources of X-ray radiation – such as “table-top” free electron lasers. However, the use of conventional undulators using permanent magnets also implies system sizes which are large. In this work, we assess the possibilities for the use of novel mini-undulators in conjunction with a LWFA so that the dimensions of the undulator become comparable with the acceleration distances for LWFA experiments (i.e., centimeters). The use of a prototype undulator using laser machining of permanent magnets for this application is described and the emission characteristics and limitations of such a system are determined. Preliminary electron propagation and X-ray emission measurements are taken with a LWFA electron beam at the University of Michigan.
The properties of the acoustic modes are sensitive to magnetic activity. The unprecedented long-term Kepler photometry, thus, allows stellar magnetic cycles to be studied through asteroseismology. We search for signatures of magnetic cycles in the seismic data of Kepler solar-type stars. We find evidence for periodic variations in the acoustic properties of about half of the 87 analysed stars. In these proceedings, we highlight the results obtained for two such stars, namely KIC 8006161 and KIC 5184732.
Perennial ryegrass varieties bred to express high water-soluble carbohydrate (WSC) concentrations have been shown to improve liveweight gain in pre-weaned lambs of grazing ewes (Lee et al., 2001) compared to conventional ryegrass. Studies have shown that the largest differential in WSC between ryegrass varieties bred for high WSC concentrations and control ryegrasses occurs 5-6 weeks after the plant is allowed to re-grow following cutting or grazing (Miller et al., 2001). Therefore, the benefits, in terms of lamb performance, of using these grasses with high WSC concentrations may be best achieved when they are rotationally rather than continuously grazed. The aim of this experiment was to compare lambs rotationally or continuously grazing either a ryegrass variety bred for high WSC concentrations or a control ryegrass.
Nutritional manipulation during the dry period can alter subsequent animal responses to feeding in terms of milk yield and composition. Previous research has shown interesting differences in milk production and composition due to energy or protein supply in the dry period (Moorby et al., 1996). The objective of this experiment was to test the interaction between energy and protein supplies during the dry period on subsequent milk production and composition. Effects on live weight gains and condition scores are reported in a separate summary (Jaurena et al., 2001).
Previous results have shown that during late gestation even under conditions of live weight (LW) gain, maternal body protein can be in negative balance due to the highly demanding gravid uterus and udder. It has also been claimed that current feeding standards underpredict dry cow nitrogen (N) requirement. Considering that it is not possible to measure maternal body N status independently of the requirements of the conceptus and the udder, estimation of conceptus and udder N requirements by mathematical models can help to predict maternal N requirement. The aim of this study was to assess cow N requirement during late gestation by predicting maternal N balance through a mathematical model. Previous results related with this study were presented in Jaurena et al, (2001).
The high intake characteristics of red clover silage has been recognised for many years (e.g. Thomas et al., 1985). Our previous study (Dewhurst et al., 2000) demonstrated the considerable intake and milk production potential of clover silages made using a new approach based on preparation of big-bales from wilted material with the use of biological inoculant additives. The objective of this study was to verify the positive results obtained with red and white clover silages using material taken from a further series of cuts taken in a subsequent year and to evaluate the legume silages with low levels of concentrate feeding.
Energy and protein supply during the dry period can affect subsequent milk production and composition (Moorby et al., 1996). Grass silage is a common ingredient of dry cow diets, but although it is usually adequate in crude protein concentration (CP), a high proportion is frequently in non-protein forms. Red clover silage has shown interesting characteristics that would increase true protein supply to ruminants (Broderick et al., 2000), which could avoid the use of more expensive concentrate supplements. The objective of this experiment was to compare red clover and ryegrass silage when fed as the sole source of forage to dry cows with a diet comprising ryegrass silage and a protein supplement.
With increasing emphasis in the meat sector on better and more consistent quality, carcass leanness and conformation is now an important issue for sheep breeders. In 1999, only 47% of all carcasses in the UK met the target specifications for weight, fat and conformation (MLC, 2000), highlighting the potential for improvement. In the current stratified crossbreeding system, crossbred wether lambs are a by-product of the production of dam line ewes for the lowland sector. If their carcass quality is sufficient, they can give a valuable boost to the economics of the breeding programme. Genetic improvement of carcass quality in crossing sire breeds would benefit the crossbred wethers, as well as filter through to the terminal sire cross lambs produced by the crossbred ewes. This work aims to assess the influence of selection index and live conformation score of crossing sires (in this case Bluefaced Leicesters) on growth and carcass quality traits of their crossbred progeny, as a first step towards designing a genetic improvement programme for crossing sire sheep.
Our earlier studies with dry cows have highlighted a number of factors that affect performance in the subsequent lactation, including forage intake in the peri-parturient period, body condition at calving and supply of Metabolisable Protein (MP) (Moorby et al., 1996; Dewhurst et al., 2000). There is now increased interest in making more use of grazed grass, as a cheap feed, particularly through extending grazing into the late-autumn and winter. Dry cows are suited to extended grazing because they do not need to be brought in for milking each day. The high voluntary intakes of grass may be beneficial for dry cows, though the low MP supply from autumn-grass might be a disadvantage. This experiment evaluated the effects of extended grazing, compared with housing and silage-feeding of dry cows.
Earlier work showed that red clover silage has considerable potential for milk production (e.g. Thomas et al., 1985), though low digestibility and difficulties ensiling clovers were seen as problems that needed to be addressed. Advances in legume breeding and conservation technology as well as a renewed emphasis on extensive organic production systems within Agenda 2000 meant that it was timely to reconsider the potential of legume silages for milk production.
Body fat and protein reserves at calving can affect milk production and composition (Garnsworthy, 1988; Moorby et al., 1996). Milk producers frequently feed their dry cows with a low quality diet to prevent them from becoming too fat before calving. However, the cow must nourish the foetus and develop mammary secretory tissues, which can be a problem if she is offered a low protein diet. This experiment was designed to test the interaction between energy and protein supplies during the dry period on changes in live weight (LW), condition score (CS) and muscle Longissimus dorsi depth (LD). Subsequent milk production and composition data are reported in a separate summary (Jaurena et al., 2001).
Genetic potential for milk production has increased rapidly in the Holstein-Friesian breed and there is concern that this might be causing an increased incidence of health problems. We have recently (Ingvartsen et al., 2002) reviewed the inter-relationships between lactation performance and health, demonstrating the importance of considering effects on/of body reserves as well as effects on/of milk production. Whilst we identified mechanisms whereby body reserves can have a direct effect on susceptibility to disease, disease also affects body reserves making it difficult to study their inter-relationships. The dry period is a particularly interesting period in this regard, because additional nutrients are directed towards reserves, whilst it is followed by a period (early lactation) of high disease incidence. The objective of this study was to investigate the effects of body condition score (BCS) at calving, as well as the effects of dry period diets designed to alter BCS, on disease incidences in the first 100 days of lactation.
Earlier studies (e.g. Dewhurst et al., 1996, 1999) have shown marked declines in forage voluntary intake as calving approaches. The resultant reduction in nutrient supply may compromise performance in the next lactation, because it coincides with a period of intense metabolic activity in preparation for the next lactation. Feeding concentrates to dry cows did not overcome this problem (Dewhurst et al., 1999). The objective of the current experiment was to investigate alternative dry cow strategies, using only high-quality grass silage, to minimise the severity and consequences for subsequent milk production of the reduction in nutrient supply in this period.
Research has shown both production and health benefits for the use of chicory (Cichorium intybus) within ruminant diets. Despite this, little was known about the effects of this forage, containing differing fatty acid profiles and secondary plant compounds compared with ryegrass, on beef stability, fatty acid composition or sensory properties. An experiment was conducted to investigate whether the inclusion of chicory in the diet of grazing beef steers would alter these three properties in the M. Longissimus muscle when compared with beef steers grazing perennial ryegrass (Lolium perenne). Triplicate 2 ha plots were established with a chicory (cv. Puna II)/perennial ryegrass mix or a perennial ryegrass control. A core group of 36 Belgian Blue – cross steers were used within a 2-year beef finishing experiment (n=6/replicate plot). In the 2nd grazing year, steers were slaughtered as they reached a target fat class of 3. Muscle pH was checked 2 and 48 h post-slaughter. A section of the hindloin joint containing the M. Longissimus lumborum muscle was removed and a 20 mm-thick steak was cut and muscle samples were taken for analysis of vitamin E and fatty acid analysis. The remaining section of the loin was vacuum packed in modified atmosphere packs and subjected to simulated retail display. A section of the conditioned loin was used for sensory analysis. Data on pH, vitamin E concentration and colour stability in a simulated retail display showed there were no effects of including chicory in the diet of grazing beef steers on meat stability. There were also no differences found in the fatty acid composition or the overall eating quality of the steaks from the two treatments. In conclusion, there were no substantive effects of including chicory in the swards of grazing beef cattle on meat stability, fatty acid composition or sensory properties of the M. Longissimus muscle when compared with beef steers grazing ryegrass-only swards.
A two-beam Martin-Puplett polarizing interferometer has been used in the rapid-scan mode on the 15 meter JCMT in conjunction with the facility detector, UKT14, to survey the solar sub-millimeter and millimeter spectrum in the four wavebands at 7-11, 11-15, 21-24 and 27-30 cm–1 to a spectral resolution of 0.01 cm–1 and at spatial resolutions of 19″, 16″, 7″ and 6″, respectively. Overall atmospheric transmission through these windows has been evaluated by comparison with synthetic spectra generated with FASCOD/HITRAN. A search has been made for contributions to these spectra from high-n transitions of H and heavier elements by several methods, including the comparison of solar with lunar and limb with disk center spectra.
We conducted a prospective cohort study between 1 January 2010 and 31 December 2012 at five adult and paediatric academic medical centres to identify factors associated with persistent methicillin-resistant Staphylococcus aureus (MRSA) colonisation. Adults and children presenting to ambulatory settings with a MRSA skin and soft tissue infection (i.e. index cases), along with household members, performed self-sampling for MRSA colonisation every 2 weeks for 6 months. Clearance of colonisation was defined as two consecutive negative sampling periods. Subjects without clearance by the end of the study were considered persistently colonised and compared with those who cleared colonisation. Of 243 index cases, 48 (19·8%) had persistent colonisation and 110 (45·3%) cleared colonisation without recurrence. Persistent colonisation was associated with white race (odds ratio (OR), 4·90; 95% confidence interval (CI), 1·38–17·40), prior MRSA infection (OR 3·59; 95% CI 1·05–12·35), colonisation of multiple sites (OR 32·7; 95% CI 6·7–159·3). Conversely, subjects with persistent colonisation were less likely to have been treated with clindamycin (OR 0·28; 95% CI 0·08–0·99). Colonisation at multiple sites is a risk factor for persistent colonisation and may require more targeted decolonisation efforts. The specific effect of clindamycin on MRSA colonisation needs to be elucidated.
The anticipated release of EnlistTM cotton, corn, and soybean cultivars likely will increase the use of 2,4-D, raising concerns over potential injury to susceptible cotton. An experiment was conducted at 12 locations over 2013 and 2014 to determine the impact of 2,4-D at rates simulating drift (2 g ae ha−1) and tank contamination (40 g ae ha−1) on cotton during six different growth stages. Growth stages at application included four leaf (4-lf), nine leaf (9-lf), first bloom (FB), FB + 2 wk, FB + 4 wk, and FB + 6 wk. Locations were grouped according to percent yield loss compared to the nontreated check (NTC), with group I having the least yield loss and group III having the most. Epinasty from 2,4-D was more pronounced with applications during vegetative growth stages. Importantly, yield loss did not correlate with visual symptomology, but more closely followed effects on boll number. The contamination rate at 9-lf, FB, or FB + 2 wk had the greatest effect across locations, reducing the number of bolls per plant when compared to the NTC, with no effect when applied at FB + 4 wk or later. A reduction of boll number was not detectable with the drift rate except in group III when applied at the FB stage. Yield was influenced by 2,4-D rate and stage of cotton growth. Over all locations, loss in yield of greater than 20% occurred at 5 of 12 locations when the drift rate was applied between 4-lf and FB + 2 wk (highest impact at FB). For the contamination rate, yield loss was observed at all 12 locations; averaged over these locations yield loss ranged from 7 to 66% across all growth stages. Results suggest the greatest yield impact from 2,4-D occurs between 9-lf and FB + 2 wk, and the level of impact is influenced by 2,4-D rate, crop growth stage, and environmental conditions.