Surgical innovation revisited: A historical narrative of the minimally invasive "Agarwal sliding-clip renorrhaphy" technique for partial nephrectomy and its application to an Australian cohort.

Objective To evaluate local clinical outcomes of sliding clip renorrhaphy, from inception to current utilization for open, laparoscopic, and robotically assisted partial nephrectomy. Methods We reviewed prospectively maintained databases of three surgeons performing partial nephrectomies with the sliding-clip technique at teaching hospitals between 2005 and 2019. Baseline characteristics, operative parameters, including surgical approach, RENAL Nephrometry Score, and post-operative outcomes, including Clavien-Dindo classification of complications, were recorded for 76 consecutive cases. We compared perioperative and 90-day events with patient and tumor characteristics, stratified by operative approach and case complexity, using Wilcoxon rank-sum test for continuous variables and the Chi-squared or Fisher's exact test, for binary and categorical variables, respectively. Results Open surgery (n = 15) reduced ischemia time and operative time, but increased hospital admission time. Pre- and post-operative estimated glomerular filtration rates did not change significantly by operative approach. Older patients (P = .007) and open surgery (P = .003) were associated with a higher rate of complications (any-grade). Six grade ≥3 complications occurred: these were associated with higher RENAL Nephrometry Score (P = .016) and higher pathological tumor stage (P = .045). Limits include smaller case volumes which incorporate the learning curve cases; therefore, these data are most applicable to lower volume teaching hospitals. Conclusion The sliding-clip technique for partial nephrectomy was first described by Agarwal et al and has low complication rates, acceptable operative time, and preserves renal function across open and minimally invasive surgeries. This series encompasses the initial learning curve with developing the technique through to present-day emergence as a routine standard of practice

A modified Delphi study to develop a practical guide for selecting patients with prostate cancer for active surveillance

This is the final version. Available on open access from BMC via the DOI in this recordAvailability of data and materials: The datasets generated and/or analysed during the current study are not publicly available as consent was not sought from participants to make data publically available. Data may be available from the corresponding author on reasonable request.Background Active surveillance (AS) is a management option for men diagnosed with lower risk prostate cancer. There is wide variation in all aspects of AS internationally, from patient selection to investigations and follow-up intervals, and a lack of clear evidence on the optimal approach to AS. This study aimed to provide guidance for clinicians from an international panel of prostate cancer experts. Methods A modified Delphi approach was undertaken, utilising two rounds of online questionnaires followed by a face-to-face workshop. Participants indicated their level of agreement with statements relating to patient selection for AS via online questionnaires on a 7-point Likert scale. Factors not achieving agreement were iteratively developed between the two rounds of questionnaires. Draft statements were presented at the face-to-face workshop for discussion and consensus building. Results 12 prostate cancer experts (9 Urologists, 2 academics, 1 radiation oncologist) participated in this study from a range of geographical regions (4 USA, 4 Europe, 4 Australia). Complete agreement on statements presented to the participants was 29.4% after Round One and 69.0% after Round Two. Following robust discussions at the face-to-face workshop, agreement was reached on the remaining statements. PSA, PSA density, Multiparametric MRI, and systematic biopsy (with or without targeted biopsy) were identified as minimum diagnostic tests required upon which to select patients to recommend AS as a treatment option for prostate cancer. Patient factors and clinical parameters that identified patients appropriate to potentially receive AS were agreed. Genetic and genomic testing was not recommended for use in clinical decision-making regarding AS. Conclusions The lack of consistency in the practice of AS for men with lower risk prostate cancer between and within countries was reflected in this modified Delphi study. There are, however, areas of common practice and agreement from which clinicians practicing in the current environment can use to inform their clinical practice to achieve the best outcomes for patients

Massless Spectra of Three Generation U(N) Heterotic String Vacua

We provide the methods to compute the complete massless spectra of a class of recently introduced supersymmetric E8 x E8 heterotic string models which invoke vector bundles with U(N) structure group on simply connected Calabi-Yau manifolds and which yield flipped SU(5) and MSSM string vacua of potential phenomenological interest. We apply Leray spectral sequences in order to derive the localisation of the cohomology groups H^i(X,V_a \times V_b), H^i(X,\bigwedge^2 V) and H^i(X,{\bf S}^2 V) for vector bundles defined via Fourier-Mukai transforms on elliptically fibered Calabi-Yau manifolds. By the method of bundle extensions we define a stable U(4) vector bundle leading to the first flipped SU(5) model with just three generations, i.e. without any vector-like matter. Along the way, we propose the notion of Lambda-stability for heterotic bundles.Comment: 48 page

Searching for the Standard Model in the String Landscape : SUSY GUTs

The goal of the present review article is to describe the ingredients necessary to find the Standard Model in the string landscape.Comment: 70 pages, 20 figures, this review article will be published in Reports on Progress in Physic

Diabetes and hypertension increase the placental and transcellular permeation of the lipophilic drug diazepam in pregnant women

Background: Previous studies carried out in our laboratories have demonstrated impaired drug permeation in diabetic animals. In this study the permeation of diazepam (after a single dose of 5 mg/day, administered intramuscularly) will be investigated in diabetic and hypertensive pregnant women.Methods: A total 75 pregnant women were divided into three groups: group 1 (healthy control, n = 31), group 2 (diabetic, n = 14) and group 3 (hypertensive, n = 30). Two sets of diazepam plasma concentrations were collected and measured (after the administration of the same dose of diazepam), before, during and after delivery. The first set of blood samples was taken from the mother (maternal venous plasma). The second set of samples was taken from the fetus (fetal umbilical venous and arterial plasma). In order to assess the effect of diabetes and hypertension on diazepam placental-permeation, the ratios of fetal to maternal blood concentrations were determined. Differences were considered statistically significant if p=0.05.Results: The diabetes and hypertension groups have 2-fold increase in the fetal umbilical-venous concentrations, compared to the maternal venous concentrations. Feto: maternal plasma-concentrations ratios were higher in diabetes (2.01 ± 1.10) and hypertension (2.26 ± 1.23) groups compared with control (1.30 ± 0.48) while, there was no difference in ratios between the diabetes and hypertension groups. Umbilical-cord arterial: venous ratios (within each group) were similar among all groups (control: 0.97 ± 0.32; hypertension: 1.08 ± 0.60 and diabetes: 1.02 ± 0.77).Conclusions: On line with our previous findings which demonstrate disturbed transcellular trafficking of lipophilic drugs in diabetes, this study shows significant increase in diazepam placental-permeation in diabetic and hypertensive pregnant women suggesting poor transcellular control of drug permeation and flux, and bigger exposure of the fetus to drug-placental transport

Non-clinical community interventions: a systematised review of social prescribing schemes

Abstract Background: This review focused on evaluation of United Kingdom social prescribing schemes published in peer-reviewed journals and reports. Schemes, including arts, books, education, and exercise ‘on prescription’ refer patients to community sources of non-clinical intervention. Method: A systematised review protocol appraised primary research material evaluating social prescribing schemes published 2000-15. Searches were performed in electronic databases using keywords, and articles were screened for evaluation of patient data, referral process, assessment method and outcomes; non-evaluated articles were excluded. Results: Of 86 schemes located including pilots, 40 evaluated primary research material: 17 used quantitative methods including six randomised controlled trials; 16 qualitative methods, and seven mixed methods; 9 exclusively involved arts on prescription. Conclusions: Outcomes included increase in self-esteem and confidence; improvement in mental wellbeing and positive mood; and reduction in anxiety, depression and negative mood. Despite positive findings, the review identifies a number of gaps in the evidence base and makes recommendations for future evaluation and implementation of referral pathways