Provision of revision knee arthroplasty services across Scotland: A national audit.

BACKGROUND: There is increasing evidence that both low surgeon and centre case volumes are associated with poorer outcomes following Revision Knee Arthroplasty (rTKA). Given the unique challenges faced in Scotland relating to funding and geography, understanding details on the complexity of cases is required to guide development of future rTKA services. METHODS: Utilising the Scottish Collaborative Orthopaedic Trainee Research Network (SCOTnet) a retrospective review of all Scottish 2019 rTKA cases was undertaken. Regional leads co-ordinated local data collection using individual case note review. The number of cases performed by regions, hospitals and individual surgeons were identified. Patient demographics and case complexity (Revision Knee Complexity Classification [RKCC]) were also collected. Results were compared against current standards. RESULTS: 17 units performed rTKA, delivered by 77 surgeons. A total of 506 cases were included. The mean age was 69 years (46% male). Revision for infection accounted for 147/506 (29%) cases. Extensor compromise was present in 35/506 (7%) and 11/506 (2%) required soft tissue reconstruction. According to the RKCC - 214/503 (43%) were classified as R1 (Less complex cases), 228/503 (45%) R2 (complex cases), and 61/503 (12%) R3 (most complex / salvage cases). 5/17 (29%) units met current national guidelines for case volume/year, with only 11/77 (14%) surgeons meeting recommended individual case volumes. 37/77 (48%) surgeons performed ≤ 2 cases per year. CONCLUSIONS: Most individual centre volumes could be increased by re-organising services or locations providing rTKA within a region. This should provide better access to Multidisciplinary Team (MDT) involvement. We recorded a significant number of very low volume surgeons (≤2 year) that is contradictory to current evidence-based practice.

Aberrant right posterior sectoral duct injury necessitating liver resection.

Aberrant insertion of the right posterior sectoral duct is a particularly hazardous variation of biliary anatomy which makes it prone to injury during laparoscopic cholecystectomy. Such injuries are challenging to manage, as multiple therapeutic options are available with no clear consensus in the literature for an optimal approach. Options include conservative management, intraoperative ligation of the injured duct, Roux-en-Y reconstruction and segmental liver resection. Most cases in the literature advocate for nonoperative management or hepaticojejunostomy. We present an unusual case of aberrant right posterior sectoral duct injury in which neither of these approaches was viable, necessitating a bi-segmental liver resection.

Kinetics of biological and chemical processes in anoxic-aerobic digestion of phosphorus rich waste activated sludge.

Because the functions of these water and resource recovery facilities (WRRFs) stretches beyond simply meeting effluent requirements (i.e., also includes optimisation of products to be generated as recovered resources), a high level of accuracy is required in using mathematical models that virtually replicate (hence predict) WRRF system responses to dynamic conditions. The currently developed mathematical models embrace the majority of advances made towards tracking nitrogen (N) and phosphorus (P) through the entire WRRF, and significant effort has been made towards calibrating them to predict realistic outcomes. This paper presents the stepwise calibration of the PWMSA model (Ikumi et al., 2015) for aerobic (AerD) and anoxic-aerobic digestion (AAD) processes, through predictions of (i) mineral precipitation potential, in isolation to biological reactions (ii) AerD bioprocesses (including nitrification, orthophosphate (OP) release, and endogenous respiration), in isolation to mineral precipitation (iii) predicted interaction of the mineral precipitation and the biological processes of organic removal and nitrification, excluding P accumulating organisms (PAOs) and polyphosphate (PP) release during AerD, (iv) replicated interaction of mineral precipitation and bioprocesses of P release and nitrification kinetics (v) predicted PAO behavioural kinetics of anaerobic OP release with acetate uptake and aerobic PP uptake, in isolation to nitrification and (vi) predicted nitrate denitrification and anoxic OP release. The calibrated kinetic parameters allowed for the model capability of reproducing the data from the key biological, physical and chemical processes occurring in the various environments of sludge treatment (aerobic, anoxic and anaerobic) within satisfactory level of accuracy.

Assessment of the Effectiveness of Combat Eyewear Protection Against Blast Overpressure.

It is unclear whether combat eyewear used by U. S. Service members is protective against blast overpressures (BOPs) caused by explosive devices. Here, we investigated the mechanisms by which BOP bypasses eyewear and increases eye surface pressure. We performed experiments and developed three-dimensional (3D) finite element (FE) models of a head form (HF) equipped with an advanced combat helmet (ACH) and with no eyewear, spectacles, or goggles in a shock tube at three BOPs and five head orientations relative to the blast wave. Overall, we observed good agreement between experimental and computational results, with average discrepancies in impulse and peak-pressure values of less than 15% over 90 comparisons. In the absence of eyewear and depending on the head orientation, we identified three mechanisms that contributed to pressure loading on the eyes. Eyewear was most effective at 0 deg orientation, with pressure attenuation ranging from 50 (spectacles) to 80% (goggles) of the peak pressures observed in the no-eyewear configuration. Spectacles and goggles were considerably less effective when we rotated the HF in the counter-clockwise direction around the superior-inferior axis of the head. Surprisingly, at certain orientations, spectacles yielded higher maximum pressures (80%) and goggles yielded larger impulses (150%) than those observed without eyewear. The findings from this study will aid in the design of eyewear that provides better protection against BOP.

Surgical management of splenic marginal zone lymphoma.

OBJECTIVES: Splenic marginal zone lymphoma (SMZL) is a rare indolent B-cell lymphoma with variable prognosis. As a result, there is sparse knowledge on the role of splenectomy and best management approaches. We aim to explore management strategies and outcomes amongst the cohort of SMZL patients at our centre. METHOD: A retrospective review of all splenectomies performed at a tertiary referral unit over a 23-year period was assessed. Immunohistochemical and pathological results of splenic samples, bone marrow biopsies, and peripheral blood were compiled. Operative management, surgical, and survival outcomes were assessed. Prognostic stratifications were applied and survival rates were calculated. RESULTS: Eight cases of SMZL from a database of 693 splenectomies were identified. All patients had intermediate/high-risk disease. All patients underwent splenectomy with one patient receiving preoperative rituximab. All patients had progression-free survival and resolution of disease. CONCLUSION: Based on the data obtained, current practice requires defined guidelines and centralised care.

A gene expression signature distinguishes innate response and resistance to proteasome inhibitors in multiple myeloma.

Extensive interindividual variation in response to chemotherapy is a major stumbling block in achieving desirable efficacy in the treatment of cancers, including multiple myeloma (MM). In this study, our goal was to develop a gene expression signature that predicts response specific to proteasome inhibitor (PI) treatment in MM. Using a well-characterized panel of human myeloma cell lines (HMCLs) representing the biological and genetic heterogeneity of MM, we created an in vitro chemosensitivity profile in response to treatment with the four PIs bortezomib, carfilzomib, ixazomib and oprozomib as single agents. Gene expression profiling was performed using next-generation high-throughput RNA-sequencing. Applying machine learning-based computational approaches including the supervised ensemble learning methods Random forest and Random survival forest, we identified a 42-gene expression signature that could not only distinguish good and poor PI response in the HMCL panel, but could also be successfully applied to four different clinical data sets on MM patients undergoing PI-based chemotherapy to distinguish between extraordinary (good and poor) outcomes. Our results demonstrate the use of in vitro modeling and machine learning-based approaches to establish predictive biomarkers of response and resistance to drugs that may serve to better direct myeloma patient treatment options.

Mobile technology in clinical teaching.

Technology is having a profound effect on education in the 21st century and nurse educators are being challenged to integrate technological innovation to assist students in their learning. This paper reports a study on the introduction of smart mobile technology to support student learning in the clinical environment. In a climate of collaborative inquiry, clinical lecturers and two researchers from the same department carried out a project in three phases: formation, implementation and analysis. Following the formation phase, six clinical lecturers adopted iPads to support their clinical teaching (implementation phase). At this time they also kept reflective journals. In the analysis phase a thematic analysis of the data from the journals and from a focus group found both enabling and constraining factors influenced the use of iPads by clinical lecturers. The themes categorised as enablers were: resources and technology; and, management and technology support. Those identified as barriers or constraining factors were: clinical staff engagement; and lecturer experience with technology. Student engagement and learning, and connectivity were both enabling and constraining factors. This paper concludes that the use of a mobile device such as an iPad can enhance teaching in clinical settings but that in order for such devices to be successfully integrated into clinical teaching consideration needs to be given to professional development needs, adequate resourcing and technology support.

Single-cell analysis of targeted transcriptome predicts drug sensitivity of single cells within human myeloma tumors.

Multiple myeloma (MM) is characterized by significant genetic diversity at subclonal levels that have a defining role in the heterogeneity of tumor progression, clinical aggressiveness and drug sensitivity. Although genome profiling studies have demonstrated heterogeneity in subclonal architecture that may ultimately lead to relapse, a gene expression-based prediction program that can identify, distinguish and quantify drug response in sub-populations within a bulk population of myeloma cells is lacking. In this study, we performed targeted transcriptome analysis on 528 pre-treatment single cells from 11 myeloma cell lines and 418 single cells from 8 drug-naïve MM patients, followed by intensive bioinformatics and statistical analysis for prediction of proteasome inhibitor sensitivity in individual cells. Using our previously reported drug response gene expression profile signature at the single-cell level, we developed an R Statistical analysis package available at https://github.com/bvnlabSCATTome, SCATTome (single-cell analysis of targeted transcriptome), that restructures the data obtained from Fluidigm single-cell quantitative real-time-PCR analysis run, filters missing data, performs scaling of filtered data, builds classification models and predicts drug response of individual cells based on targeted transcriptome using an assortment of machine learning methods. Application of SCATT should contribute to clinically relevant analysis of intratumor heterogeneity, and better inform drug choices based on subclonal cellular responses.

Risk factors for post-thyroidectomy haematoma.

BACKGROUND: There has been increasing emphasis on performing 'same-day' or 'out-patient' thyroidectomy to reduce associated costs. However, acceptance has been limited by the risk of potentially life-threatening post-operative bleeding. This study aimed to review current rates of post-operative bleeding in a metropolitan teaching hospital and identify risk factors. METHOD: Medical records of patients undergoing thyroidectomy between January 2007 and March 2012 were reviewed retrospectively. Pre-operative, operative and pathological data, and post-operative complication data, were examined. RESULTS: The study comprised 205 thyroidectomy cases. Mean age was 51.6 years (standard deviation = 14.74), with 80 per cent females. Unilateral thyroidectomy was performed in 81 cases (39.5 per cent) and total thyroidectomy was performed in 74 cases (36.1 per cent; 5.3 per cent with concomitant lymph node dissection). Nine patients (4.4 per cent) suffered post-operative bleeding, of which six required re-operation. Analysis showed that post-operative systolic blood pressure of 180 mmHg or greater was associated with post-operative bleeding (p = 0.003, chi-square test). CONCLUSION: Rates of significant post-operative bleeding are consistent with recent literature. Post-operative hypertension, diabetes and high post-operative drain output were identified as independent risk factors on multivariate analysis; when identified, these may be caveats to same-day discharge of thyroidectomy patients.

Biodegradability of wastewater and activated sludge organics in anaerobic digestion.

The investigation provides experimental evidence that the unbiodegradable particulate organics fractions of primary sludge and waste activated sludge calculated from activated sludge models remain essentially unbiodegradable in anaerobic digestion. This was tested by feeding the waste activated sludge (WAS) from three different laboratory activated sludge (AS) systems to three separate anaerobic digesters (AD). Two of the AS systems were Modified Ludzack - Ettinger (MLE) nitrification-denitrification (ND) systems and the third was a membrane University of Cape Town (UCT) ND and enhanced biological P removal system. One of the MLE systems and the UCT system were fed the same real settled wastewater. The other MLE system was fed raw wastewater which was made by adding a measured constant flux (gCOD/d) of macerated primary sludge (PS) to the real settled wastewater. This PS was also fed to a fourth AD and a blend of PS and WAS from settled wastewater MLE system was fed to a fifth AD. The five ADs were each operated at five different sludge ages (10-60d). From the measured performance results of the AS systems, the unbiodegradable particulate organic (UPO) COD fractions of the raw and settled wastewaters, the PS and the WAS from the three AS systems were calculated with AS models. These AS model based UPO fractions of the PS and WAS were compared with the UPO fractions calculated from the performance results of the ADs fed these sludges. For the PS, the UPO fraction calculated from the AS and AD models matched closely, i.e. 0.30 and 0.31. Provided the UPO of heterotrophic (OHO, fE_OHO) and phosphorus accumulating (PAO, fE_PAO) biomass were accepted to be those associated with the death regeneration model of organism "decay", the UPO of the WAS calculated from the AS and AD models also matched well - if the steady state AS model fE_OHO = 0.20 and fE_PAO = 0.25 values were used, then the UPO fraction of the WAS calculated from the AS models deviated significantly from those calculated with the AD models. Therefore in plant wide wastewater treatment models the characterization of PS and WAS as defined by the AS models can be applied without modification in AD models. The observed rate limiting hydrolysis/acidogenesis rates of the sludges are listed.

Alteration of the amount and morphology of wear particles by the addition of loading profile transitions during artificial hip wear testing.

Current validation tests of total hip arthroplasty endo-prostheses capture only a single activity performed by patients: continuous walking. A more representative test that includes transitions from a static loaded position to dynamic motion would simulate common motions by patients in which they change from standing to walking. The introduction of such transitions into a traditional test protocol could provide insight into actual wear behaviours and more realistic wear particle properties such as size and shape. First, the introduction of transitions will increase the measured wear rate. Second, the amount of wear will be positively correlated to the number of transitions per day. Finally, the size and shape of polyethylene particle produced via testing with transitions will differ from those of a conventional continuous walking test. Three identical sets of four cobalt chromium femoral heads and sterilized acetabular cups sterilized in ethylene oxide were tested in 30 per cent bovine serum under three conditions: continuous walking (0 transitions/day), 10 transitions/day, and 100 transitions/day. A day was defined as 2500 steps. The static and peak dynamic loads were 260 N and 1.9 kN respectively. A testing duration of 106 cycles was completed for each of the three tests. The wear rate was found to be inversely related to the number of transitions. Particle analysis showed that the particle size decreased as the number of transitions increased. Particles from the 100 transitions/day test were more fibular and produced more particles of the size known to promote an immune reactive response. Contrary to our hypothesis, as the number of transitions performed by patients increased, the wear rate and accumulated wear decreased. In addition, as the number of transitions increased, a larger percentage of wear particles were in the submicron size range. Consequently, despite a decrease in wear due to the presence of loading profile transitions, there is a potentially greater risk of osteolysis owing to the increased production of immunoreactive particles.

Euthanasia and assisted suicide: comparison of legal aspects in Switzerland and other countries.

The purpose of this paper is to present the legal aspects associated with assisted suicide in Switzerland and compare them with those in other countries. Like euthanasia, assisted suicide is a subject that induces much discussion in many countries. While the law is very liberal in some countries, such as Belgium and the Netherlands (where both euthanasia and assisted suicide take place), these practices are very controversial in other countries, such as France, where they remain taboo subjects. In the United States of America, the laws concerning assisted suicide can differ greatly from one state to another. For example, in Oregon, assisted suicide is allowed if applied by a medical doctor; in others, this act is illegal. In Canada, it is punishable according to the Criminal Code. In Switzerland euthanasia is punishable by law. However, the penal code does not condemn assisted suicide, whether carried out by a medical doctor or another person, provided it is not carried out through selfish motives. The application of these practices has become simplified in recent years and societies for the right to die with dignity based on this principle have come into being (Exit and Dignitas). In the French- and German-speaking parts of Switzerland the association Exit assists individuals living in Switzerland with serious progressive and incurable disease in their engagement to end their life. The association Dignitas, in the German-speaking part of Switzerland, also undertakes--in the same circumstances--to assist individuals coming from foreign countries. Dignitas welcomes several such individuals every year, especially from Germany, where a similar approach does not currently exist.

Intravenous administration of an AAV-2 vector for the expression of factor IX in mice and a dog model of hemophilia B.

Previous experiments have demonstrated the stable expression of factor IX (FIX) protein in mice and canine models of hemophilia B following portal vein gene transfer with a recombinant adeno-associated virus (rAAV) vector encoding FIX. Here, we present the results of studies that further optimized the rAAV vector transgene cassette used to express FIX and explored the use of the less-invasive intravenous (i.v.) route of vector administration for the treatment of hemophilia B. First, a liver-specific promoter was evaluated in conjunction with cis-acting regulatory elements in mice. Constructs that included both the beta-globin intron and the woodchuck hepatitis virus post-transcriptional regulatory element resulted in the highest level of FIX expression in vivo. Using this optimized vector, we demonstrate that i.v. injection was feasible for hepatic gene transfer in mice, achieving 70-80% of portal vein expression levels of FIX. In further studies using the Chapel Hill strain of hemophilia B dogs, we demonstrate for the first time FIX expression and partial correction of the bleeding disorder following i.v. administration of an AAV vector.

Huntington's disease: do future physicians and lawyers think eugenically?

The availability of presymptomatic and prenatal genetic tests could give rise to societal pressures on persons at risk for Huntington's disease (HD). The objective of this study was to identify future lawyers' and physicians' views on eugenics and genetic testing for HD. Five-hundred and ninety-nine Swiss law students and advanced medical students from 11 courses received teaching about HD and patient autonomy. They filled out questionnaires after having seen an audio/video recording of an interview with an HD mutation carrier. Participation rates were 68-97%. Attitudes of future lawyers and physicians were significantly different for most questions: 73.2% of law students vs 39.4% of medical students agreed that society should do everything possible to diminish the frequency of HD, including non-governmental pressure on carriers to undergo systematic genetic testing and recommendation of sterilization; 94% of all students agreed to the systematic proposal of prenatal testing to all women at risk; and 83.4% of medical students, but only 40.3% of law students, agreed that the wishes of a person at risk not to have her/himself and future children tested must be entirely respected. More education is needed to discourage eugenic pressures and discrimination of persons at risk of HD and other genetic diseases.

Should cancer patients be informed about their diagnosis and prognosis? Future doctors and lawyers differ.

OBJECTIVES: To compare attitudes of medical and law students toward informing a cancer patient about diagnosis and prognosis and to examine whether differences are related to different convictions about benefit or harm of information. SETTING AND DESIGN: Anonymous questionnaires were distributed to convenience samples of students at the University of Geneva containing four vignettes describing a cancer patient who wishes, or alternatively, who does not wish to be told the truth. PARTICIPANTS: One hundred and twenty seven medical students and 168 law students. MAIN OUTCOME MEASURES: Five point Likert scale of responses to the vignettes ranging from "certainly inform" to "certainly not inform" the patient. RESULTS: All medical students and 96% of law students favoured information about the diagnosis of cancer if the patient requests it. Seventy four per cent of medical students and 82% of law students favoured informing a cancer patient about his or her prognosis (p = 0.0003). Thirty five per cent of law students and 11.7% of medical students favoured telling about the diagnosis (p = 0.0004) and 25.6% of law students and 7% of medical students favoured telling about the prognosis (p < 0.0001) even if the patient had clearly expressed his wish not to be informed. Law students indicated significantly more often than medical students reasons to do with the patient's good, legal obligations, and the physician's obligation to tell the truth, and significantly less often than medical students that their attitude had been determined predominantly by respect for the autonomous choice of the patient. CONCLUSION: Differences in attitudes according to the type of case and the type of studies were related to convictions about the benefit or harm to the patient caused by being given information. The self reported reasons of future physicians and future lawyers are helpful when considering means to achieve a better acceptance of patients' right to know and not to know.

Terminally ill patients and Jehovah's Witnesses: teaching acceptance of patients' refusals of vital treatments.

OBJECTIVES: To find out whether and how the teaching of medical ethics can influence attitudes on accepting treatment refusals. SETTING AND DESIGN: Anonymous questionnaires were distributed to 4 groups of students at the University of Geneva who had participated (P) or not (nP) in teaching modules on medical law and ethics. One vignette described a terminally ill patient refusing mechanical ventilation, another a Jehovah's Witness refusing a life-saving blood transfusion. PARTICIPANTS: 127 medical and 168 law students. MAIN OUTCOME MEASURES: 5-point Likert scale of responses to the vignettes reaching from certain acceptance to certain non-acceptance of the treatment refusal. RESULTS: More than 80% of law students (nP) said that a good physician should accept the terminally ill patient's refusal. 84% (P) compared to 68% (nP) of medical students (P=0.03) would accept this refusal. The acceptance of the Jehovah's Witness refusal of a life-saving transfusion was less among all students. Students from the groups (P) reported significantly more often (P < 0.001) that they would accept (76% of medical students) or that a good physician should accept (63% of law students) the treatment refusal of the Jehovah's Witness than medical students (48%) and law students (27%) from the two other groups (nP). CONCLUSION: (P) students showed significantly more acceptance of treatment refusals in the hypothetical case scenarios than (nP) students from the same faculty. Religion, cultural origin and school education of the parents had less influence on attitudes than participation in ethical teaching and type of student (medicine vs. law).

Signaling and antiproliferative effects mediated by GnRH receptors after expression in breast cancer cells using recombinant adenovirus.

GnRH receptors (GnRH-Rs) are found in human cancers, including those of the breast, and GnRH can inhibit the growth of cell lines derived from such cancers. Although pituitary and extrapituitary GnRH-R transcripts appear identical, their functional characteristics may differ. Most extrapituitary GnRH-Rs have low affinity for GnRH analogs and may not activate PLC or discriminate between agonists and antagonists in the same way as pituitary GnRH-Rs. Here we have assessed whether GnRH-Rs expressed exogenously in breast cancer cells differ from those in gonadotropes. We found no evidence for endogenous GnRH-Rs in MCF7 cells, but after infection with adenovirus expressing the GnRH-R (Ad GnRH-R) at a multiplicity of infection of 10 or greater, at least 80% expressed GnRH-Rs. These had high affinity (K(d) for [(125)I]buserelin, 1.4 nM) and specificity (rank order of potency, buserelin>GnRH>>chicken GnRH-II) and mediated stimulation of [(3)H]IP accumulation. Increasing viral titer [from multiplicity of infection, 3-300] increased receptor number (10,000-225,000 sites/cell) and [(3)H]IP responses. GnRH stimulated ERK2 phosphorylation in Ad GnRH-R-infected cells, and this effect, like stimulation of [(3)H]IP accumulation, was blocked by GnRH-R antagonists. GnRH also inhibited [(3)H]thymidine incorporation into Ad GnRH-R-infected cells (but not control cells). This effect was mimicked by agonist analogs and inhibited by two antagonists. Thus, when exogenous GnRH-Rs are expressed at density comparable to that in gonadotropes, they are functionally indistinguishable from the endogenous GnRH-Rs in gonadotropes, and increasing expression of high affinity GnRH-Rs can dramatically enhance the direct antiproliferative effect of GnRH agonists on breast cancer cells.