Site-saturation studies of β-lactamase: Production and characterization of mutant β-lactamases with all possible amino acid substitutions at residue 71

A mutagenic technique that "saturates" a particular site in a protein with all possible amino acid substitutions was used to study the role of residue 71 in β-lactamase (EC 3.5.2.6). Threonine is conserved at residue 71 in all class A β-lactamases and is adjacent to the active site Ser-70. All 19 mutants of the enzyme were characterized by the penam and cephem antibiotic resistance they provided to Escherichia coli LS1 cells. Surprisingly, cells producing any of 14 of the mutant β-lactamases displayed appreciable resistance to ampicillin; only cells with mutants having Tyr, Trp, Asp, Lys, or Arg at residue 71 had no observable resistance to ampicillin. However, the mutants are less stable to cellular proteases than wild-type enzyme is. These results suggest that Thr-71 is not essential for binding or catalysis but is important for stability of the β-lactamase protein. An apparent change in specificity indicates that residue 71 influences the region of the protein that accommodates the side chain attached to the β-lactam ring of the substrate

Market-Based Instruments for the Optimal Control of Invasive Insect Species: B. Tabaci in Arizona

Invasive insect species represent perhaps one of the most significant potential sources of economic risk to U.S. agricultural production. Private control of invasive insect species is likely to be insufficient due to negative externality and weaker-link public good problems. In this study, we compare a system of Pigouvian taxes with tradable permits for invasive species control. While the emissions control literature shows that taxes are preferred to permits under cost uncertainty, invasive-species control involves correlated cost and benefit uncertainty. Hence, we expect a quantity-based system to be preferred. Monte Carlo simulations of optimal steady-state outcomes confirm our expectations.externalities, invasive species, optimal control, permits, spatial-temporal model, taxes, Crop Production/Industries, Resource /Energy Economics and Policy,

Market-Based Instruments for the Optimal Control of Invasive Insect Species: B. Tabaci in Arizona

Invasive insect species represent perhaps one of the most significant potential sources of economic risk to U.S. agricultural production. Private control of invasive insect species is likely to be insufficient due to negative externality and weaker-link public good problems. In this study, we compare a system of Pigouvian taxes with tradable permits for invasive species control. While the emissions control literature shows that taxes are preferred to permits under cost uncertainty, invasive species control involves correlated cost and benefit uncertainty, so we expect a quantity-based system to be preferred. Monte Carlo simulations of optimal steady-state outcomes confirm our expectations.externalities, invasive species, optimal control, permits, spatial-temporal model, taxes., Environmental Economics and Policy, Public Economics, Risk and Uncertainty, H23, L51, Q28, Q57.,

Developing teaching for mathematical resilience in further education

The construct ‘Mathematical Resilience’ [1] has been developed to describe a positive stance towards mathematics; resilient learners develop approaches to mathematical learning which help them to overcome the affective barriers and setbacks that can be part of learning mathematics for many people. A resilient stance towards mathematics can be engineered by a strategic and explicit focus on the culture of learning mathematics within both formal and informal learning environments. As part of that engineering, we have developed the notion of ‘Teaching for Mathematical Resilience’. The work described here is focused on developing teachers who know how explicitly to develop resilient learners of mathematics. Teachers for Mathematical Resilience develop a group culture of ‘can do’ mathematics which works to counter the prevalent culture of mathematics helplessness and mathematics anxiety in the general population when faced with mathematical ideas. This paper discusses the changes in awareness brought about by a one-day course designed to develop ‘teaching for mathematical resilience’. The course presentations ran between November 2015 and July 2016 and recruited participants who work as teachers of numeracy or mathematics in Further Education (FE) institutions in England – predominantly in the Midlands. Many of these teachers were being required to teach beyond their own level of mathematical confidence. The data shows that it is possible within a one day course to increase teachers’ awareness of negative past experiences as a possible cause of difficulty with mathematics; teachers become aware of how patterns of behaviour such as avoidance and disruption may have developed as safe-preservation habits and how mathematics anxiety can be transmitted from teacher to student in a vicious cycle. Teachers are supported to work through personal anxieties towards mathematics in a safe and collaborative environment and to develop elements of personal mathematical resilience and awareness of the affective domain. Thus we have sought to break the cycle of mathematics anxiety by educating teacher awareness. However, we have also found that many UK FE teachers request and would likely benefit from further courses

Early discharge hospital at home

Background: Early discharge hospital at home is a service that provides active treatment by healthcare professionals in the patient's home for a condition that otherwise would require acute hospital inpatient care. This is an update of a Cochrane review. Objectives To determine the effectiveness and cost of managing patients with early discharge hospital at home compared with inpatient hospital care. Search methods We searched the following databases to 9 January 2017: the Cochrane Effective Practice and Organisation of Care Group (EPOC) register, Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, CINAHL, and EconLit. We searched clinical trials registries. Selection criteria Randomised trials comparing early discharge hospital at home with acute hospital inpatient care for adults. We excluded obstetric, paediatric and mental health hospital at home schemes. Data collection and analysis We followed the standard methodological procedures expected by Cochrane and EPOC. We used the GRADE approach to assess the certainty of the body of evidence for the most important outcomes. Main results: We included 32 trials (N = 4746), six of them new for this update, mainly conducted in high-income countries. We judged most of the studies to have a low or unclear risk of bias. The intervention was delivered by hospital outreach services (17 trials), community-based services (11 trials), and was co-ordinated by a hospital-based stroke team or physician in conjunction with community-based services in four trials. Studies recruiting people recovering from stroke: Early discharge hospital at home probably makes little or no difference to mortality at three to six months (risk ratio (RR) 0.92, 95% confidence interval (CI) 0.57 to 1.48, N = 1114, 11 trials, moderate-certainty evidence) and may make little or no difference to the risk of hospital readmission (RR 1.09, 95% CI 0.71 to 1.66, N = 345, 5 trials, low-certainty evidence). Hospital at home may lower the risk of living in institutional setting at six months (RR 0.63, 96% CI 0.40 to 0.98; N = 574, 4 trials, low-certainty evidence) and might slightly improve patient satisfaction (N = 795, low-certainty evidence). Hospital at home probably reduces hospital length of stay, as moderate-certainty evidence found that people assigned to hospital at home are discharged from the intervention about seven days earlier than people receiving inpatient care (95% CI 10.19 to 3.17 days earlier, N = 528, 4 trials). It is uncertain whether hospital at home has an effect on cost (very low-certainty evidence). Studies recruiting people with a mix of medical conditions: Early discharge hospital at home probably makes little or no difference to mortality (RR 1.07, 95% CI 0.76 to 1.49; N = 1247, 8 trials, moderate-certainty evidence). In people with chronic obstructive pulmonary disease (COPD) there was insufficient information to determine the effect of these two approaches on mortality (RR 0.53, 95% CI 0.25 to 1.12, N = 496, 5 trials, low-certainty evidence). The intervention probably increases the risk of hospital readmission in a mix of medical conditions, although the results are also compatible with no difference and a relatively large increase in the risk of readmission (RR 1.25, 95% CI 0.98 to 1.58, N = 1276, 9 trials, moderate-certainty evidence). Early discharge hospital at home may decrease the risk of readmission for people with COPD (RR 0.86, 95% CI 0.66 to 1.13, N = 496, 5 trials low-certainty evidence). Hospital at home may lower the risk of living in an institutional setting (RR 0.69, 0.48 to 0.99; N = 484, 3 trials, low-certainty evidence). The intervention might slightly improve patient satisfaction (N = 900, low-certainty evidence). The effect of early discharge hospital at home on hospital length of stay for older patients with a mix of conditions ranged from a reduction of 20 days to a reduction of less than half a day (moderate-certainty evidence, N = 767). It is uncertain whether hospital at home has an effect on cost (very low-certainty evidence). Studies recruiting people undergoing elective surgery: Three studies did not report higher rates of mortality with hospital at home compared with inpatient care (data not pooled, N = 856, low-certainty evidence; mainly orthopaedic surgery). Hospital at home may lead to little or no difference in readmission to hospital for people who were mainly recovering from orthopaedic surgery (N = 1229, low-certainty evidence). We could not establish the effects of hospital at home on the risk of living in institutional care, due to a lack of data. The intervention might slightly improve patient satisfaction (N = 1229, low-certainty evidence). People recovering from orthopaedic surgery allocated to early discharge hospital at home were discharged from the intervention on average four days earlier than people allocated to usual inpatient care (4.44 days earlier, 95% CI 6.37 to 2.51 days earlier, , N = 411, 4 trials, moderate-certainty evidence). It is uncertain whether hospital at home has an effect on cost (very low-certainty evidence). Authors' conclusions: Despite increasing interest in the potential of early discharge hospital at home services as a less expensive alternative to inpatient care, this review provides insufficient evidence of economic benefit (through a reduction in hospital length of stay) or improved health outcomes

Implications of the problem orientated medical record (POMR) for research using electronic GP databases: a comparison of the Doctors Independent Network Database (DIN) and the General Practice Research Database (GPRD).

Background The General Practice Research Database (GPRD) and Doctor's Independent Network Database (DIN), are large electronic primary care databases compiled in the UK during the 1990s. They provide a valuable resource for epidemiological and health services research. GPRD (based on VAMP) presents notes as a series of discrete episodes, whereas DIN is based on a system (MEDITEL) that used a Problem Orientated Medical Record (POMR) which links prescriptions to diagnostic problems. We have examined the implications for research of these different underlying philosophies. Methods Records of 40,183 children from 141 practices in DIN and 76,310 from 464 practices in GRPD who were followed to age 5 were used to compare the volume of recording of prescribing and diagnostic codes in the two databases. To assess the importance and additional value of the POMR within DIN, the appropriateness of diagnostic linking to skin emollient prescriptions was investigated. Results Variation between practices for both the number of days on which prescriptions were issued and diagnoses were recorded was marked in both databases. Mean number of "prescription days" during the first 5 years of life was similar in DIN (19.5) and in GPRD (19.8), but the average number of "diagnostic days" was lower in DIN (15.8) than in GPRD (22.9). Adjustment for linkage increased the average "diagnostic days" to 23.1 in DIN. 32.7% of emollient prescriptions in GPRD appeared with an eczema diagnosis on the same day compared to only 19.4% in DIN; however, 86.4% of prescriptions in DIN were linked to an earlier eczema diagnosis. More specifically 83% of emollient prescriptions appeared under a problem heading of eczema in the 121 practices that were using problem headings satisfactorily. Conclusion Prescribing records in DIN and GPRD are very similar, but the usage of diagnostic codes is more parsimonious in DIN because of its POMR structure. Period prevalence rates will be underestimated in DIN unless this structure is taken into account. The advantage of the POMR is that in 121 of 141 practices using problem headings as intended, most prescriptions can be linked to a problem heading providing a specific reason for their issue

Federal Grant Applications: What You Need to Know Before You Start Writing

Sometimes disaster relief arrives as a US Department of Agriculture (USDA) grant, and there may be more grants resulting from the COVID-19 pandemic. While obtaining a grant is appealing, many producers overlook grant application details causing many grant proposals to be rejected immediately, before they are read or considered. The checklist provided by this brief will help producers prepare grant applications and avoid common pitfalls

Improved ruminant genetics: Implementation guidance for policymakers and investors

Genetics makes use of natural variation among animals. Selecting preferred animals as parents can yield permanent and cumulative improvements in the population. More efficient animals can greatly reduce greenhouse gas emissions and feed costs. Breeding, including cross-breeding between indigenous and imported species, can also improve resilience to diseases and heat stress and increase reproductive performance

Detection and drivers of exposure and effects of pharmaceuticals in higher vertebrates

Pharmaceuticals are highly bioactive compounds now known to be widespread environmental contaminants. However, research regarding exposure and possible effects in non-target higher vertebrate wildlife remains scarce. The fate and behaviour of most pharmaceuticals entering our environment via numerous pathways remain poorly characterized, and hence our conception and understanding of the risks posed to wild animals is equally constrained. The recent decimation of Asian vulture populations owing to a pharmaceutical (diclofenac) offers a notable example, because the exposure route (livestock carcasses) and the acute toxicity observed were completely unexpected. This case not only highlights the need for further research, but also the wider requirement for more considered and comprehensive ‘ecopharmacovigilance’. We discuss known and potential high risk sources and pathways in terrestrial and freshwater ecosystems where pharmaceutical exposure in higher vertebrate wildlife, principally birds and mammals, may occur. We examine whether approaches taken within existing surveillance schemes (that commonly target established classes of persistent or bioaccumulative contaminants) and the risk assessment approaches currently used for pesticides are relevant to pharmaceuticals, and we highlight where new approaches may be required to assess pharmaceutical-related risk