Deconstruction of plant biomass by a Cellulomonas strain isolated from an ultra-basic (lignin-stripping) spring.

Plant material falling into the ultra-basic (pH 11.5-11.9) springs within The Cedars, an actively serpentinizing site in Sonoma County, California, is subject to conditions that mimic the industrial pretreatment of lignocellulosic biomass for biofuel production. We sought to obtain hemicellulolytic/cellulolytic bacteria from The Cedars springs that are capable of withstanding the extreme alkaline conditions wherein calcium hydroxide-rich water removes lignin, making cell wall polysaccharides more accessible to microorganisms and their enzymes. We enriched for such bacteria by adding plant debris from the springs into a synthetic alkaline medium with ground tissue of the biofuel crop switchgrass (Panicum virgatum L.) as the sole source of carbon. From the enrichment culture we isolated the facultative anaerobic bacterium Cellulomonas sp. strain FA1 (NBRC 114238), which tolerates high pH and catabolizes the major plant cell wall-associated polysaccharides cellulose, pectin, and hemicellulose. Strain FA1 in monoculture colonized the plant material and degraded switchgrass at a faster rate than the community from which it was derived. Cells of strain FA1 could be acclimated through subculturing to grow at a maximal concentration of 13.4% ethanol. A strain FA1-encoded β-1, 4-endoxylanase expressed in E. coli was active at a broad pH range, displaying near maximal activity at pH 6-9. Discovery of this bacterium illustrates the value of extreme alkaline springs in the search for microorganisms with potential for consolidated bioprocessing of plant biomass to biofuels and other valuable bio-inspired products

Non-compliance with clinical guidelines increases the risk of complications after primary total hip and knee joint replacement surgery

Background Total hip and total knee replacement (THR/TKR) are common and effective surgeries to reduce the pain and disability associated with arthritis but are associated with small but significant risks of preventable complications such as surgical site infection (SSI) and venous-thrombo-embolism (VTE). This study aims to determine the degree to which hospital care was compliant with clinical guidelines for the prevention of SSI and VTE after THR/TKR; and whether non-compliant prophylaxis is associated with increased risk of complications. Methods and findings A prospective multi-centre cohort study was undertaken in consenting adults with osteoarthritis undergoing elective primary TKR/THR at one of 19 high-volume Australian public or private hospitals. Data were collected prior to surgery and for one-year post-surgery. Four adjusted logistic regression analyses were undertaken to explore associations between binary non-compliance and the risk of surgical complications: (1) composite (simultaneous) non-compliance with both (VTE and antibiotic) guidelines and composite complications [all-cause mortality, VTE, readmission/reoperation for joint-related reasons (one-year) and non-joint-related reasons (35-days)], (2) VTE non-compliance and VTE outcomes, (3) antibiotic non-compliance and any SSI, and (4) antibiotic non-compliance and deep SSI. Data were analysed for 1875 participants. Guideline non-compliance rates were high: 65% (VTE), 87% (antibiotics) and 95% (composite guideline). Composite non-compliance was not associated with composite complication (12.8% vs 8.3%, adjusted odds ratio [AOR] = 1.41, 95%CI 0.68–3.45, p = 0.40). Non-compliance with VTE guidelines was associated with VTE outcomes (5% vs 2.4%, AOR = 2.83, 95%CI 1.59–5.28,p < 0.001). Non-compliance with antibiotic guidelines was associated with any SSI (14.8% vs 6.1%, AOR = 1.98, 95%CI 1.17–3.62,p = 0.02) but not deep infection (3.7% vs 1.2%,AOR = 2.39, 95%CI 0.85–10.00, p = 0.15). Conclusions We found high rates of clinical variation and statistically significant associations between non-compliance with VTE and antibiotic guidelines and increased risk of VTE and SSI, respectively. Complications after THR/TKR surgery may be decreased by improving compliance with clinical guidelines

Associations between pre-surgical daily opioid use and short-term outcomes following knee or hip arthroplasty : a prospective, exploratory cohort study

Background: Retrospective studies have found that daily opioid use pre-arthroplasty predicts worse longer-term service, clinical and patient-reported outcomes. Prospective studies are needed to confirm these observations. This prospective, exploratory study aimed to determine: the proportion of total knee or hip arthroplasty (TKA, THA) patients who use opioids regularly (daily) pre-surgery; if opioid use pre-surgery is associated with acute and sub-acute outcomes to 12-weeks post-surgery. Methods: Consecutive patients undergoing primary TKA or THA were prospectively enrolled pre-surgery and followed-up by telephone to 12-weeks post-surgery. Acute-care (oral morphine equivalent dosage (OMED), length of stay, discharge to inpatient rehabilitation, complications) and 12-week outcomes (Oxford Knee or Hip Score, Euroqol 'today' health score, current use of opioids, and complications including readmissions) were monitored. Unadjusted and adjusted Odds Ratios (ORs) (95% Confidence Interval, CI), Rate Ratios and β coefficients (standard error) were calculated. Results: Five Hundred Twenty-One patients were included (TKA n = 381). 15.7% (95%CI 12.6 to 18.9) used opioids regularly pre-surgery. 86.8% (452/521) were available for follow-up at 12-weeks. In unadjusted analyses, pre-surgical opioid use was significantly associated with higher average acute daily OMED [β 0.40 (0.07), p < 0.001], presence of an acute complication [OR 1.75 (1.02 to 3.00)], and ongoing use of opioids at 12-weeks [OR 5.06 (2.86 to 8.93)]. After adjusting for covariates, opioid use pre-surgery remained significantly associated with average acute daily OMED [β 0.40 (0.07), p < 0.001] and ongoing use at 12-weeks [OR 5.38 (2.89 to 9.99)]. Conclusion: People who take daily opioids pre-surgery have significantly greater odds for greater opioid consumption acutely and ongoing use post-surgery. Adequately powered prospective studies are required to confirm whether pre-surgical opioid use is or is not associated with poorer joint and quality of life scores or a complication in the short-term

Association between VTE and antibiotic prophylaxis guideline compliance and patient-reported outcomes after total hip and knee arthroplasty : an observational study

Background: Surgical site infection (SSI) and venous thromboembolism (VTE) are associated with high burden and cost and are considered largely preventable following total knee or hip arthroplasty (TKA, THA). The risk of developing VTE and SSI is reduced when prophylaxis is compliant with evidence-based clinical guidelines. However, the association between VTE and antibiotic prophylaxis clinical guideline compliance and patient-reported outcome measures (PROMs) after THA/TKA is unknown. This study aims to explore whether care that is non-compliant with VTE and antibiotic guideline recommendations is associated with PROMs (Oxford Hip/Knee Score and EQ-5D Index scores) at 90- and 365-days after surgery. Methods: This prospective observational study included high-volume arthroplasty public and private sites and consenting eligible participants undergoing elective primary THA/TKA. We conducted multiple linear regression and linear mixed-effects modelling to explore the associations between non-compliance with VTE and antibiotic guidelines, and PROMs. Results: The sample included 1838 participants. Compliance with VTE and antibiotic guidelines was 35% and 13.2% respectively. In adjusted modelling, non-compliance with VTE guidelines was not associated with 90-day Oxford score (β = − 0.54, standard error [SE] = 0.34, p = 0.112) but was significantly associated with lower (worse) 365-day Oxford score (β = − 0.76, SE = 0.29, p = 0.009), lower EQ-5D Index scores at 90- (β = − 0.02 SE = 0.008, p = 0.011) and 365-days (β = − 0.03, SE = 0.008, p = 0.002). The changes in Oxford and EQ-5D Index scores were not clinically important. Noncompliance with antibiotic guidelines was not associated with either PROM at 90- (Oxford: β = − 0.45, standard error [SE] = 0.47, p = 0.341; EQ-5D: β = − 0.001, SE = 0.011, p = 0.891) or 365-days (Oxford score: β = − 0.06, SE = 0.41, p = 0.880 EQ-5D: β = − 0.010, SE = 0.012, p = 0.383). Results were consistent when complications were included in the model and in linear mixed-effects modelling with the insurance sector as a random effect. Conclusions: Non-compliance with VTE prophylaxis guidelines, but not antibiotic guidelines, is associated with statistically significant but not clinically meaningful differences in Oxford scores and EQ-5D Index scores at 365 days

Developing physical activity interventions for adults with spinal cord injury. Part 2: Motivational counseling and peer-mediated interventions for people intending to be active

Objective: The majority of people with spinal cord injury (SCI) do not engage in sufficient leisure-time physical activity (LTPA) to attain fitness benefits; however, many have good intentions to be active. This paper describes two pilot interventions targeting people with SCI who are insufficiently active but intend to be active (i.e., intenders ). Method: Study 1 examined the effects of a single, telephone-based counseling session on self-regulatory efficacy, intentions, and action plans for LTPA among seven men and women with paraplegia or tetraplegia. Study 2 examined the effects of a home-based strengthtraining session, delivered by a peer and a fitness trainer, on strength-training task self-efficacy, intentions, action plans, and behavior. Participants were 11 men and women with paraplegia. Results: The counseling session (Study 1) yielded medium- to large-sized increases in participants\u27 confidence to set LTPA goals and intentions to be active. The home visit (Study 2) produced medium- to large-sized increases in task self-efficacy, barrier self-efficacy, intentions, action planning, and strength-training behavior from baseline to 4 weeks after the visit. Conclusions/Implications: Study 1 findings provide preliminary evidence that a single counseling session can impact key determinants of LTPA among intenders with SCI. Study 2 findings demonstrate the potential utility of a peer-mediated, home-based strength training session for positively influencing social cognitions and strength-training behavior. Together, these studies provide evidence and resources for intervention strategies to promote LTPA. among intenders with SCI, a population for whom LTPA interventions and resources are scarcely available. © 2013 American Psychological Association

Pharmacists in Pharmacovigilance: Can Increased Diagnostic Opportunity in Community Settings Translate to Better Vigilance?

The pharmacy profession has undergone substantial change over the last two to three decades. Whilst medicine supply still remains a central function, pharmacist’s roles and responsibilities have become more clinic and patient focused. In the community (primary care), pharmacists have become important providers of healthcare as Western healthcare policy advocates patient self-care. This has resulted in pharmacists taking on greater responsibility in managing minor illness and the delivery of public health interventions. These roles require pharmacists to more fully use their clinical skills, and often involve diagnosis and therapeutic management. Community pharmacists are now, more than ever before, in a position to identify, record and report medication safety incidents. However, current research suggests that diagnostic ability of community pharmacists is questionable and they infrequently report to local or national schemes. The aim of this paper is to highlight current practice and suggest ways in which community pharmacy can more fully contribute to patient safety

Implementing early mobilisation after knee or hip arthroplasty to reduce length of stay : a quality improvement study with embedded qualitative component

Background: Models of care for managing total knee or hip arthroplasty (TKA, THA) incorporating early mobilisation are associated with shorter acute length-of-stay (LOS). Few studies have examined the effect of implementing early mobilisation in isolation, however. This study aimed to determine if an accelerated mobilisation protocol implemented in isolation is associated with a reduced LOS without undermining care. Method: A Before-After (quasi-experimental) study was used. Standard practice pre-implementation of the new protocol was physiotherapist-led mobilisation once per day commencing on post-operative Day 1 (Before phase). The new protocol (After phase) aimed to mobilise patients four times by end of Day 2 including an attempt to commence on Day 0; physiotherapy weekend coverage was necessarily increased. Poisson regression modelling was used to determine associations between study period and LOS. Additional outcomes to 12 weeks post-surgery were monitored to identify unintended consequences of the new protocol. Time to first mobilisation (hours) and proportion mobilising Day 0 were monitored to assess protocol compliance. An embedded qualitative component captured staff perspectives of the new protocol. Results: Five hundred twenty consecutive patients (n = 278, Before; n = 242, After) were included. The new protocol was associated with no change in unadjusted LOS, a small reduction in adjusted LOS (8.1%, p = 0.046), a reduction in time to first mobilisation (28.5 (10.8) vs 22.6 (8.1) hrs, p < 0.001), and an increase in the proportion mobilising Day 0 (0 vs 7%, p < 0.001). Greater improvements were curtailed by an unexpected decrease in physiotherapy staffing (After phase). There were no significant changes to the rates of complications or readmissions, joint-specific pain and function scores or health-related quality of life to 12 weeks post-surgery. Qualitative findings of 11 multidisciplinary team members highlighted the importance of morning surgery, staffing, and well-defined roles. Conclusion: Small reductions in LOS are possible utilising an early mobilisation protocol in isolation after TKA or THA although staff burden is increased likely undermining both sustainability and the magnitude of the change. Simultaneous incorporation of other changes within the pathway would likely secure larger reductions in LOS

Critical Reflections on Methodological Challenge in Arts and Dementia Evaluation and Research

Methodological rigour, or its absence, is often a focus of concern for the emerging field of evaluation and research around arts and dementia. However, this paper suggests that critical attention should also be paid to the way in which individual perceptions, hidden assumptions and underlying social and political structures influence methodological work in the field. Such attention will be particularly important for addressing methodological challenges relating to contextual variability, ethics, value judgement, and signification identified through a literature review on this topic. Understanding how, where and when evaluators and researchers experience such challenges may help to identify fruitful approaches for future evaluation. This paper is based upon a presentation on the subject given at the First International Research Conference on the Arts and Dementia: Theory, Methodology and Evidence on 9 March 2017

Response and Acquired Resistance to Everolimus in Anaplastic Thyroid Cancer

Everolimus, an inhibitor of the mammalian target of rapamycin (mTOR), is effective in treating tumors harboring alterations in the mTOR pathway. Mechanisms of resistance to everolimus remain undefined. Resistance developed in a patient with metastatic anaplastic thyroid carcinoma after an extraordinary 18-month response. Whole-exome sequencing of pretreatment and drug-resistant tumors revealed a nonsense mutation in TSC2, a negative regulator of mTOR, suggesting a mechanism for exquisite sensitivity to everolimus. The resistant tumor also harbored a mutation in MTOR that confers resistance to allosteric mTOR inhibition. The mutation remains sensitive to mTOR kinase inhibitors

The Oxytricha trifallax Mitochondrial Genome

The Oxytricha trifallax mitochondrial genome contains the largest sequenced ciliate mitochondrial chromosome (∼70 kb) plus a ∼5-kb linear plasmid bearing mitochondrial telomeres. We identify two new ciliate split genes (rps3 and nad2) as well as four new mitochondrial genes (ribosomal small subunit protein genes: rps- 2, 7, 8, 10), previously undetected in ciliates due to their extreme divergence. The increased size of the Oxytricha mitochondrial genome relative to other ciliates is primarily a consequence of terminal expansions, rather than the retention of ancestral mitochondrial genes. Successive segmental duplications, visible in one of the two Oxytricha mitochondrial subterminal regions, appear to have contributed to the genome expansion. Consistent with pseudogene formation and decay, the subtermini possess shorter, more loosely packed open reading frames than the remainder of the genome. The mitochondrial plasmid shares a 251-bp region with 82% identity to the mitochondrial chromosome, suggesting that it most likely integrated into the chromosome at least once. This region on the chromosome is also close to the end of the most terminal member of a series of duplications, hinting at a possible association between the plasmid and the duplications. The presence of mitochondrial telomeres on the mitochondrial plasmid suggests that such plasmids may be a vehicle for lateral transfer of telomeric sequences between mitochondrial genomes. We conjecture that the extreme divergence observed in ciliate mitochondrial genomes may be due, in part, to repeated invasions by relatively error-prone DNA polymerase-bearing mobile elements