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Basal cell carcinoma is the most common cancer. Excisional surgery is associated with a high clearance rate, at the expense of significant functional and aesthetic morbidity, especially within the T-zone or for extensive lesions. We report five-year follow-up outcomes for carbon dioxide laser extirpation of cutaneous basal cell carcinoma, assisted by immediate methyl aminolevulinate photodynamic therapy and cost-benefit considerations. Retrospective cohort database analysis of adult patients with biopsy-proven primary cutaneous basal cell carcinoma, completing five years of follow-up. Direct per-lesion cost was compared with conventional wide local excision. Patients with morphoeic basal cell carcinoma were excluded. Treated lesions were up to 1% total body surface area and up to 3.8mm (1.38 ± 0.695cm, mean ± standard deviation) in biopsy-proven depth. At the five-year follow-up mark, 93.6% of treated areas remained free of recurrence. Nodular basal cell carcinoma was the most common subtype (41.5%). A mean tumour depth greater than 2 ± 0.872mm was significantly associated with recurrence (Mann-Whitney, = 0.0487). For a service delivered through the NHS at 2015 prices, we report a 43% saving, equating to a saving of £235 per basal cell carcinoma or a national annualised saving of £70 million by 2025 for the NHS. Our results suggest that CO -assisted photodynamic therapy is non-inferior to excision but may offer better functional and cosmetic preservation at a fraction of the direct like for like cost of operative surgery. Investigation of this method by randomised controlled methodology is warranted.

Golfing history was made last week when the US Supreme Court ruled that a disabled professional golfer can ride around golf links in a cart, rather than be made to walk the courses. In a questionnaire survey of 278 Finnish women and their partners, psychologists identified several factors that increase pregnancy related anxiety and fear of vaginal delivery (British Journal of Obstetrics and Gynaecology 2001;108:492-8).

Symplectic N-body integrators are widely used to study problems in celestial mechanics. The most popular algorithms are of 2nd and 4th order, requiring 2 and 6 substeps per timestep, respectively. The number of substeps increases rapidly with order in timestep, rendering higher-order methods impractical. However, symplectic integrators are often applied to systems in which perturbations between bodies are a small factor of the force due to a dominant central mass. In this case, it is possible to create optimized symplectic algorithms that require fewer substeps per timestep. This is achieved by only considering error terms of order epsilon, and neglecting those of order epsilon^2, epsilon^3 etc. Here we devise symplectic algorithms with 4 and 6 substeps per step which effectively behave as 4th and 6th-order integrators when epsilon is small. These algorithms are more efficient than the usual 2nd and 4th-order methods when applied to planetary systems.

Given the impressive investment by the nation in observational Astronomy and Astrophysics facilities coming on line now and in the near future, we advocate for an increased investment in applied and fundamental research on Astrophysical and Celestial Dynamics (ACD). Specifically we call for a) continued and expanded support for applied research in ACD, b) creation of support for fundamental research in ACD and its subfields, and c) the creation of a unified program to help scientists coordinate and collaborate in their research in these fields. The benefits of this proposal are threefold. First, it will enable researchers to interpret and understand the implications of newly observed phenomena that will invariably arise from new facilities and surveys. Second, research on fundamentals will foster connections between specialists, leveraging advances found in one sub-field and making them available to others. Third, a coordinated approach for applied and fundamental research in ACD will help academic institutions in the United States to produce future researchers trained and knowledgeable in essential subfields such as Mathematical Celestial Mechanics and able to continue its advancement in conjunction with the increase in observations.

Although intratumor heterogeneity has been inferred in multiple myeloma (MM), little is known about its subclonal phylogeny. To describe such phylogenetic trees in a series of patients with MM, we perform whole-exome sequencing and single-cell genetic analysis. Our results demonstrate that at presentation myeloma is composed of two to six different major clones, which are related by linear and branching phylogenies. Remarkably, the earliest myeloma-initiating clones, some of which only had the initiating t(11;14), were still present at low frequencies at the time of diagnosis. For the first time in myeloma, we demonstrate parallel evolution whereby two independent clones activate the RAS/MAPK pathway through RAS mutations and give rise subsequently to distinct subclonal lineages. We also report the co-occurrence of RAS and interferon regulatory factor 4 ( IRF4 ) p.K123R mutations in 4% of myeloma patients. Lastly, we describe the fluctuations of myeloma subclonal architecture in a patient analyzed at presentation and relapse and in NOD/SCID-IL2Rγ null xenografts, revealing clonal extinction and the emergence of new clones that acquire additional mutations. This study confirms that myeloma subclones exhibit different survival properties during treatment or mouse engraftment. We conclude that clonal diversity combined with varying selective pressures is the essential foundation for tumor progression and treatment resistance in myeloma.

The measurement and treatment of acute pain in animals is essential from a welfare perspective. Valid pain-related outcome measures are also crucial for ensuring reliable and translatable findings in veterinary clinical trials. The short form of the Glasgow Composite Measure Pain Scale (CMPS-SF) is a multi-item behavioral pain assessment tool, developed and validated using a psychometric approach, to measure acute pain in the dog. Here we conduct a scoping review to identify prospective research studies that have used the CMPS-SF. We aim to describe the contexts in which it has been used, verify the correct use of the scale, and examine whether these studies are well - designed and adequately powered. We identify 114 eligible studies, indicating widespread use of the scale. We also document a limited number of modifications to the scale and intervention level, which would alter its validity. A variety of methods, with no consensus, were used to analyse data derived from the scale. However, we also find many deficiencies in reporting of experimental design in terms of the observers used, the underlying hypothesis of the research, the statement of primary outcome, and the use of a priori sample size calculations. These deficiencies may predispose to both type I and type II statistical errors in the small animal pain literature. We recommend more robust use of the scale and derived data to ensure success of future studies using the tool ensuring reliable and translatable outcomes.

Lyme disease cases reported in seven Canadian provinces from 2009 to 2019 through the Lyme Disease Enhanced Surveillance System are described herein by demographic, geography, time and season. The proportion of males was greater than females. Bimodal peaks in incidence were observed in children and older adults (≥60 years of age) for all clinical signs except cardiac manifestations, which were more evenly distributed across age groups. Proportions of disease stages varied between provinces: Atlantic provinces reported mainly early Lyme disease, while Ontario reported equal proportions of early and late-stage Lyme disease. Early Lyme disease cases were mainly reported between May through November, whereas late Lyme disease were reported in December through April. Increased awareness over time may have contributed to a decrease in the proportion of cases reporting late disseminated Lyme disease. These analyses help better describe clinical features of reported Lyme disease cases in Canada.

Background: The most commonly used predictive equation for basal metabolic rate (BMR) is the Schofield equation, which only uses information on body weight, age and sex to derive the prediction. However, because body composition is a key influencing factor, there will be error in calculating an individual's basal requirements based on this prediction. Objective: To investigate whether adding additional anthropometric measures to the standard measures can enhance the predictability of BMR and to cross-validate this within a separate subgroup. Design: Cross-sectional study of 150 Caucasian adults from Scotland, with a body mass index range of 16.7-49.3 kg/m2. All subjects underwent measurement of BMR, body composition, and 148 also had basic skinfold and circumference measures taken. The resultant equation was tested in a subgroup of 39 obese males. Results: The average difference between the predicted (Schofield equation) and measured BMR was 502 kJ/day. There was a slight systematic bias in this error, with the Schofield equation underestimating the lowest values. The average discrepancy between predicted and actual BMR was reduced to 452 kJ/day, with the addition of fat mass, fat-free mass, an overall 10% improvement on the Schofield equation (P=0.054). Using an equation derived from principal components analysis of anthropometry measurements similarly decreased the difference to 458 kJ/day (P=0.039). Testing the equation in a separate group indicated a 33% improvement in predictability of BMR, compared to the Schofield equation. Conclusions: In the absence of detailed information on body composition, utilizing anthropometric data provides a useful alternative methodology to improve the predictability of BMR beyond that achieved from the standard Schofield prediction equation. This should be confirmed in more individuals, both within the obese and normal weight category.