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Chromosome axis-associated HORMA domain proteins (HORMADs), e.g. ASY1 in Arabidopsis, are crucial for meiotic recombination. ASY1, as other HORMADs, is assembled on the axis at early meiosis and depleted when homologous chromosomes synapse. Puzzlingly, both processes are catalyzed by AAA+ ATPase PCH2 together with its cofactor COMET. Here, we show that the ASY1 remodeling complex is temporally and spatially differently assembled. While PCH2 and COMET appear to directly interact in the cytoplasm in early meiosis, PCH2 is recruited by the transverse filament protein ZYP1 and brought to the ASY1-bound COMET assuring the timely removal of ASY1 during chromosome synapsis. Since we found that the PCH2 homolog TRIP13 also binds to the ZYP1 homolog SYCP1 in mouse, we postulate that this mechanism is conserved among eukaryotes. Deleting the PCH2 binding site of ZYP1 led to a failure of ASY1 removal. Interestingly, the placement of one obligatory crossover per homologous chromosome pair, compromised by ZYP1 depletion, is largely restored in this separation-of-function zyp1 allele suggesting that crossover assurance is promoted by synapsis. In contrast, this zyp1 allele, similar to the zyp1 null mutant, showed elevated type I crossover numbers indicating that PCH2-mediated eviction of ASY1 from the axis restricts crossover formation., (© The Author(s) 2022. Published by Oxford University Press on behalf of Nucleic Acids Research.)

Background: Healthcare events related to diabetic foot disease carry a burden of morbidity, mortality and economic cost. Prompt identification of clinical infection with appropriate tissue sampling limits use of broad spectrum empirical antibiotics and improves antibiotic stewardship. Staphylococcus aureus remains the commonest infecting organism and high-dose flucloxacillin remains the empirical antibiotic of choice for antibiotic naïve patients. Barriers to microbe-specific treatment include: adequate tissue sampling, delays in culture results, drug allergies and the emergence of multidrug-resistant organisms which can complicate the choice of targeted antibiotics. Even appropriate antibiotic treatment carries a risk of adverse events including the selection of resistant organisms., Aims: Multidisciplinary clinical assessment of a diabetic foot infection is supported by the use of appropriate imaging modalities and deep tissue sampling, both of which are encouraged to enhance sampling accuracy. Narrow-spectrum, high dose, short duration antimicrobial therapy is ideal. Further clarity in these areas would be of benefit to clinicians involved in management of diabetic foot infections., Methods: A combination of literature review with expert discussion was used to generate consensus on management of diabetic foot infection, with a specific focus on empirical antimicrobial therapy., Results: Gram positive organisms represent the commonest pathogens in diabetic foot infection. However there are developing challenges in antimicrobial resistance and antibiotic availability., Discussion: Recommendations for empirical therapy, including the choice of alternative oral agents and use of outpatient antibiotics would be of benefit to those involved in diabetic foot care., Conclusion: This paper provides advice on empirical antibiotic therapy that may be used as a framework for local guideline development to support clinicians in the management of diabetic foot infection., (© 2017 John Wiley & Sons Ltd.)

Quality improvement depends on data collection and audit of clinical services to inform clinical improvements. Various steps in the care of the diabetic foot can be used to audit a service but need defined audit standards. A diabetes foot service should have risk stratification system in place that should compare to the population-based figures of 76% having low-risk feet, 17% moderate risk and 7% being at high risk of ulceration. Resources can then be directed towards those with high-risk feet. Prevalence of foot ulceration needs to be audited. Community-based studies give an audit standard of around 2%, with 2 to 9% having had an ulcer at some stage in the past. Amputation rates should be easier to measure, and the best results are reported to be around 1.5-3 per 1000 people with diabetes. This is a useful benchmark figure, and the rate has been shown to decrease by approximately a third over the last 15 years in some centres. Ulceration rates and ulcer healing rates are the ultimate outcome audit measure as they are always undesirable, whilst occasionally for defined individuals, an amputation can be a good outcome. In addition to clinical outcomes, processes of care can be audited such as provision of clinical services, time from new ulcer to be seen by health care professional, inpatient foot care or use of antibiotics. Measurement of clinical services can be a challenge in the diabetic foot, but it is essential if clinical services and patient outcomes are to be improved., (Copyright © 2016 John Wiley & Sons, Ltd.)

Objective: To establish the incidence of nontraumatic lower-extremity amputation (LEA) in people with diabetes in Scotland., Research Design and Methods: This cohort study linked national morbidity records and diabetes datasets to establish the number of people with diabetes who underwent nontraumatic major and minor LEA in Scotland from 2004 to 2008., Results: Two thousand three hundred eighty-two individuals with diabetes underwent a nontraumatic LEA between 2004 and 2008; 57.1% (n = 1,359) underwent major LEAs. The incidence of any LEA among persons with diabetes fell over the 5-year study period by 29.8% (3.04 per 1,000 in 2004 to 2.13 per 1,000 in 2008, P < 0.001). Major LEA rates decreased by 40.7% from 1.87 per 1,000 in 2004 to 1.11 per 1,000 in 2008 (P < 0.001)., Conclusions: There has been a significant reduction in the incidence of LEA in persons with diabetes in Scotland between 2004 and 2008, principally explained by a reduction in major amputation.

The Scottish Diabetes Foot Action Group (SDG) has developed and introduced a national strategy plan for diabetic foot care across Scotland. This has involved the implementation of an evidence-based national foot screening and risk stratification programme that has already covered 61% of the population in just the first two years. Nationally agreed patient information foot leaflets and professional education material have been introduced, and a consensus for antibiotic use in the diabetic foot has been published. Information on multidisciplinary specialist foot services has been collected, indicating that 58% of Health Board areas have consultants with dedicated sessions in their job plan to a foot clinic, and 42% had integrated orthotic involvement. The SDG aims to increase these figures. Work has been undertaken to support local podiatry networks and improve communication between the specialist centre and the community. At a national level the SDG is working with Foot in Diabetes UK (FDUK) to recognize key podiatry skills by developing core competencies and a competency framework for the diabetes podiatrist and diabetes orthotist. The annual Scottish Diabetes Survey indicates some improvement in amputation rates with prevalence decreasing from 0.8% to 0.5%, and improved recording of foot ulceration at a national level. This national strategy has helped highlight the importance and difficulties facing diabetes foot care and should help to continue to improve the quality of care of people with diabetes who have foot-related problems.

Aims: We aimed to identify which individual risk factors best predict foot ulceration in routine clinical practice and whether an integrated clinical tool is a better screening tool for future foot ulceration., Methods: Routinely collected clinical information on foot and general diabetes indicators were recorded on the regional diabetes electronic register. Follow-up data on foot ulceration were collected from the same electronic record, the local multidisciplinary foot clinic and community and hospital podiatry paper records. Data were electronically linked to see which criteria best predicted future foot ulceration., Results: Foot risk scores were recorded on 3719 patients (44% female, mean age 59±15years) across community and hospital clinics. Overall, 851 (22.9%) had insensitivity to monofilaments, in 629 (17.2%) both pulses were absent and 184 (4.9%) had a prior ulcer. In multivariate analysis, the strongest predictors of foot ulceration were prior ulcer, insulin treatment, absent monofilaments, structural abnormality and proteinuria and retinopathy. The sensitivity of predicting foot ulceration was 52% for prior ulcer, 61% for absent monofilaments, 75% for 'high risk' on an integrated risk score and 91% for high and moderate risk combined. The corresponding specificities were 99, 81, 89 and 61%. Positive likelihood ratio was 52 for prior ulcer and 6.8 for foot risk, with negative likelihood ratios of 0.48 and 0.15, respectively., Conclusions: Integrated foot risk scores are more sensitive than individual clinical criteria in predicting future foot ulceration and are likely to be better screening tools, where excluding false negative results is of paramount importance., (© 2011 The Authors. Diabetic Medicine © 2011 Diabetes UK.)

We report on an universal method to achieve and sustain a large mode-hop free tuning range of an external cavity diode laser. By locking one of the resonators using a closed loop control based on polarization spectroscopy while tuning the laser we achieved mode-hop free tuning of up to 130 GHz with a non AR-coated, off-the-shelf laser diode.

Exposure duration has been found to have a strong impact on the affective value attributed to a variety of stimuli. The purpose of the study reported here was to examine the impact of this variable in projective testing, and im particular in the affective value subjects attribute to the TAT cards. Using 34 undergraduate students, a linear decrease in pleasantness was found as a function of exposure duration. Factors leading to variation in exposure duration might therefore be confounded with the interpretations made of a subject's protocol. It was suggested that the time a subject views a projective test stimulus should be controlled in the administration.

The mediating role of learning in the relationship between repeated exposure and affect was explored and supported in three experiments involving a total of 229 undergraduate participants. It was found that both learning and affect measures behaved in essentially the same way as a function of exposure duration (Experiments 1 and 3), serial position (Experiments 1 and 2), rating delay (Experiment 1) and stimulus properties (Experiment 1). These results suggest learning may be intrinsically rewarding and clarify one of the mechanisms involved in the relationship between exposure frequency and affect, extending Berlyne's two-factor theory of the effects of stimulus familiarity.