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Objectives To report our experience of bladder urothelial cell carcinoma (UCC) in children and review contemporary management and follow-up of paediatric UCC. Patients and methods Between 2004 and 2020, five patients (4 boys and 1 girl) were managed at our centre for urothelial cell carcinoma of the bladder. Data was collected by note review for age at presentation, symptoms, clinical findings, investigations, treatment and follow-up. Results All five patients presented with visible haematuria, two had dysuria and one had suprapubic pain. Bladder ultrasound scan (USS) showed exophytic bladder lesions in only 4 patients. Definitive diagnosis and treatment were achieved by cystoscopic excision. Four patients had PUNLMP while one had Grade 3 pTa UCC of the bladder which required further cystoscopic excision and intravesical Mitomycin C (MMC) instillation. All patients were followed up clinically, with renal USS and cystoscopy. We have observed recurrence of the carcinoma in two patients requiring further cystoscopic excision and intravesical MMC. Conclusion Bladder urothelial cell carcinoma in children should be suspected in children presenting with haematuria. If renal USS is normal, cystoscopy should be considered for diagnosis and treatment. Compared to adults, children with bladder UCC often have favourable histopathology and prognosis. Close follow-up is necessary with renal USS and cystoscopy to detect recurrence even in PUNLMP.

Contains fulltext : 244686.pdf (Publisher’s version ) (Open Access) Cloacal malformations are among the most complex types of anorectal malformation and are characterized by the urological, genital, and intestinal tracts opening through a single common channel in the perineum. Long-term outcome is affected by multiple factors, which include anatomical variants of the malformation itself, associated anomalies, and the surgical approach. Reconsidering these variables and their influence on "patient important" function might lead to strategies that are more outcome-driven than focused on the creation of normal anatomy. Key outcomes reflect function in each of the involved tracts and the follow-up needed should therefore not only include the classical fields of colorectal surgery and urology but also focus on items such as gynecology, sexuality, family-building, and quality of life as well as other psychological aspects. Involving patients and families in determining optimal treatment strategies and outcome measures could lead to improved outcomes for the individual patient. A strategy to support delivery of personalized care for patients with cloacal malformations by aiming to define the best functional outcomes achievable for any individual, then select the treatment pathway most likely deliver that, with the minimum morbidity and cost, would be attractive. Combining the current therapies with ongoing technological advances such as tissue expansion might be a way to achieve this.

Background: The Global Matrix 4.0 on physical activity (PA) for children and adolescents was developed to achieve a comprehensive understanding of the global variation in children’s and adolescents’ (5–17 y) PA, related measures, and key sources of influence. The objectives of this article were (1) to summarize the findings from the Global Matrix 4.0 Report Cards, (2) to compare indicators across countries, and (3) to explore trends related to the Human Development Index and geo-cultural regions. Methods: A total of 57 Report Card teams followed a harmonized process to grade the 10 common PA indicators. An online survey was conducted to collect Report Card Leaders’ top 3 priorities for each PA indicator and their opinions on how the COVID-19 pandemic impacted child and adolescent PA indicators in their country. Results: Overall Physical Activity was the indicator with the lowest global average grade (D), while School and Community and Environment were the indicators with the highest global average grade (C+). An overview of the global situation in terms of surveillance and prevalence is provided for all 10 common PA indicators, followed by priorities and examples to support the development of strategies and policies internationally. Conclusions: The Global Matrix 4.0 represents the largest compilation of children’s and adolescents’ PA indicators to date. While variation in data sources informing the grades across countries was observed, this initiative highlighted low PA levels in children and adolescents globally. Measures to contain the COVID-19 pandemic, local/international conflicts, climate change, and economic change threaten to worsen this situation.

To produce a best practice consensus guideline for the conduct of scrotal exploration for suspected testicular torsion using formal consensus methodology.A panel of 16 expert urologists, representing adult, paediatric, general, and andrological urology used the RAND/UCLA Appropriateness Consensus Methodology to score a 184 statement pre-meeting questionnaire on the conduct of scrotal exploration for suspected testicular torsion. The collated responses were presented at a face-to-face online meeting and each item was rescored anonymously after a group discussion, facilitated by an independent chair with expertise in consensus methodology. Items were scored for agreement and consensus and the items scored with consensus were used to derive a set of best practice guidelines.Statements scored as with consensus increased from Round 1 (122/184, 66.3%) to Round 2 (149/200, 74.5%). Recommendations were generated in ten categories: consent, assessment under anaesthetic, initial incision, intraoperative decision making, fixation, medical photography, closure, operation note, logistics and follow-up after scrotal exploration. Our statements assume that the decision to operate has already been made. Key recommendations in the consent process included the discussion of the possibility of orchidectomy and the possibility of subsequent infection of the affected testis or wound requiring antibiotic therapy. If after the examination under anaesthesia, the index of suspicion of testicular torsion is lower than previously thought, then the surgeon should still proceed to scrotal exploration as planned. A flow chart guiding decision making dependent on intraoperative findings has been designed. If no torsion is present on exploration and the bell clapper deformity is absent, the testis should not be fixed. When fixing a testis using sutures, 3 or 4-point is acceptable and non-absorbable sutures are preferred.We have produced consensus recommendations to inform best practice in the conduct of scrotal exploration for suspected testicular torsion.

This study aims to explore the perceptions of foundation doctors (FDs) in the United Kingdom (UK) surrounding raising concerns in the workplace. An online survey was sent to all FDs in the UK between February and March 2018. Respondents were asked what they had observed or experienced that had been ethically challenging during their foundation training. The qualitative responses were coded into themes. Reasons why FDs wished to raise concerns in the workplace included disagreements about clinical decisions within the team, insufficient availability of resources, lack of senior colleague support and having to work beyond their competencies. Challenges faced by FDs when raising concerns included organisational resistance to change, difficulties in communicating ideas to those higher up in the hierarchy and the emotional stress of whistleblowing regarding senior colleagues. Perceived consequences of raising concerns included negative impact on FDs’ reputation and career, and fear of bullying. To overcome these barriers, changes within organisations at all levels must take place in order to provide an environment where FDs are encouraged to raise concerns and thus make positive changes to their work environments for themselves, their colleagues and patients.

Large technology and software engineering programmes, such as enterprise system pro- grammes, are increasingly implemented through a mixture of customer and specialist third-party resources. These multi-partner working environments can be thought of as a complex social system, which oftentimes experience various forms of conflict. This can be due to competing objectives and priorities of the various organizations, along with incompatibilities of team members within the work-based social network of the implementation programme. If not brought under control, conflict can lead to complex emergent behaviours and dynamics within the wider social network, which can severely impact the likelihood of successful programme implementation of these software-intensive systems. Using social network analysis and thematic coding analysis within a case study, we show that the project management of complex software-intensive implementations requires considerable focus on control and communication across the programme-wide social network of team members, which we represent as a cybernetic system. A conceptual framework has been developed that extends extant literature around conflict in teams by framing the individual projects and the overall programme-wide implementation as cybernetic systems. The conceptual framework illustrates how a cybernetics approach to conflict within enterprise system implementations, can provide new insights into how conflict develops within project teams. Finally, we argue that the cybernetic approach allows us to develop project management interventions to mitigate the risk of conflict development, or control and regulate conflict once it has developed. We conclude by setting the agenda for future research on how conflict can be controlled within the implementation of software-intensive systems, such as enterprise systems.

Background: Heritability explains 45-82% of muscle mass and strength variation, yet polygenic models for muscle phenotypes in older women are scarce. Therefore, the objective of the present study was to (1) assess if total genotype predisposition score (GPSTOTAL) for a set of polymorphisms differed between older women with low and high muscle mass, and (2) utilise a data-driven GPS (GPSDD) to predict the variance in muscle size and strength-related phenotypes. Methods: In three-hundred 60- to 91-year-old Caucasian women (70.7 ± 5.7 years), skeletal muscle mass, biceps brachii thickness, vastus lateralis anatomical cross-sectional area (VLACSA), hand grip strength (HGS), and elbow flexion (MVCEF) and knee extension (MVCKE) maximum voluntary contraction were measured. Participants were classified as having low muscle mass if the skeletal muscle index (SMI) < 6.76 kg/m2 or relative skeletal muscle mass (%SMMr) < 22.1%. Genotyping was completed for 24 single-nucleotide polymorphisms (SNPs). GPSTOTAL was calculated from 23 SNPs and compared between the low and high muscle mass groups. A GPSDD was performed to identify the association of SNPs with other skeletal muscle phenotypes. Results: There was no significant difference in GPSTOTAL between low and high muscle mass groups, irrespective of classification based on SMI or %SMMr. The GPSDD model, using 23 selected SNPs, revealed that 13 SNPs were associated with at least one skeletal muscle phenotype: HIF1A rs11549465 was associated with four phenotypes and, in descending number of phenotype associations, ACE rs4341 with three; PTK2 rs7460 and CNTFR rs2070802 with two; and MTHFR rs17421511, ACVR1B rs10783485, CNTF rs1800169, MTHFR rs1801131, MTHFR rs1537516, TRHR rs7832552, MSTN rs1805086, COL1A1 rs1800012, and FTO rs9939609 with one phenotype. The GPSDD with age included as a predictor variable explained 1.7% variance of biceps brachii thickness, 12.5% of VLACSA, 19.0% of HGS, 8.2% of MVCEF, and 9.6% of MVCKE. Conclusions: In older women, GPSTOTAL did not differ between low and high muscle mass groups. However, GPSDD was associated with muscle size and strength phenotypes. Further advancement of polygenic models to understand skeletal muscle function during ageing might become useful in targeting interventions towards older adults most likely to lose physical independence. ispartof: GENES vol:13 issue:6 ispartof: location:Switzerland status: published

We evaluated the efficacy and safety outcomes of endoscopic intradetrusor botulinum toxin A (BTA) injections for the treatment of children with neuropathic bladder (NB) and non-neuropathic bladder (NNB) with or without detrusor overactivity in a single centre with a retrospective analysis. For the period 2006–2015, children who received BTA in our hospital were analysed. They were divided into group 1, those with underlying NB and group 2, those without a clear neuropathic cause of symptoms (NNB). Data are given as percentages or medians (interquartile range). Over the study period, 52 children (28 boys, 54%) received BTA, 28 in group 1 (54%; 17 (61%) boys) and 24 in group 2 (46%; 11 (46%) boys). Age at first injection was 11.8 (9.5–14.4) years. After initial injection, 40 (77%) reported symptomatic improvement, 17 (43%) becoming dry. There was no significant difference in response to initial injection between groups (p = 0.11). Duration of improvement after first injection was 7 (5.8–14) months. Twenty-five (48%) had further injections, of whom 3 (12%) were initial non-responders. Ongoing improvement was reported in 20 (80%), 11 (44%) of whom were dry. There was no significant difference in overall response to injections between groups (p = 0.11). Of the 11 non-responders, none (0/3) improved after subsequent injection and 3 (27%) subsequently underwent major urological surgery. Of the 40 who responded, 2 (5%) underwent major surgery. BTA injection produced symptomatic improvement in 77% of our study population, with no significant differences in response between NB and NNB groups. In 95% of those who improved, major urinary tract procedures were avoided during the period studied. None of the initial non-responders improved after subsequent BTA injection. BTA injection is effective and reliable in the management of children with NB and NNB refractory to medical therapy.

Background The evidence base underlying clinical practice in children’s general surgery is poor and high-quality collaborative clinical research is required to address current treatment uncertainties. The aim of this study was, through a consensus process, to identify research priorities for clinical research in this field amongst surgeons who treat children. Methods Questions were invited in a scoping survey amongst general surgeons and specialist paediatric surgeons. These were refined by the study team and subsequently prioritized in a two-stage modified Delphi process. Results In the scoping survey, a total of 226 questions covering a broad scope of children’s elective and emergency general surgery were submitted by 76 different clinicians. These were refined to 71 research questions for prioritization. A total of 168 clinicians took part in stage one of the prioritization process, and 157 in stage two. A ‘top 10’ list of priority research questions was generated for both elective and emergency general surgery of childhood. These cover a range of conditions and concepts, including inguinal hernia, undescended testis, appendicitis, abdominal trauma and enhanced recovery pathways. Conclusion Through consensus amongst surgeons who treat children, 10 priority research questions for each of the elective and emergency fields have been identified. These should provide a basis for the development of high-quality multicentre research projects to address these questions, and ultimately improve outcomes for children requiring surgical care.

War and asymmetrical conflicts are becoming increasingly prevalent in the modern world. Due to improvements in conflict medicine, survivable injuries are now more severe than they once were. Therefore, it is now more important than ever that there exist scientific and engineering methods for replicating wartime injuries in the context of the laboratory. We have developed one such method: a shock tube platform for testing ex vivo samples of the porcine respiratory system. Using this platform, we can, to some extent, simulate the pathophysiological consequences of blast lung. This is a condition commonly present in victims of explosive blasts, both those due to typical armaments and Improvised Explosive Devices (IEDs). Presented here are the results of experiments conducted using porcine bronchiole tissue as ex vivo organ cultures. Data presented show epithelial damage, consistent with known trauma-induced cell injury that can lead to acute respiratory distress syndrome (ARDS).

BACKGROUND: Congenital portosystemic shunt (cPSS) is one of the most common congenital disorders diagnosed in dogs. Hepatic encephalopathy (HE) is a frequent complication in dogs with a cPSS and is a major cause of morbidity and mortality. Despite HE been a major cause of morbidity in dogs with a cPSS, little is known about the cellular changes that occur in the central nervous system of dogs with a cPSS.OBJECTIVES: The objective of this study was to characterise the histological changes in the cerebral cortex and cerebellum of dogs with cPSS with particular emphasis on astrocyte morphology.METHODS: Eight dogs with a confirmed cPSS were included in the study.RESULTS: Six dogs had substantial numbers of Alzheimer type II astrocytes and all cases had increased immunoreactivity for glial fibrillary acidic protein in the cerebral cortex, even if there were minimal other morphological changes.CONCLUSIONS: This study demonstrates that dogs with a cPSS have marked cellular changes in the cerebral cortex and cerebellum. The cellular changes that occur in the cerebral cortex and cerebellum of dogs with spontaneously arising HE are similar to changes which occur in humans with HE, further validating dogs with a cPSS as a good model for human HE.

The complexity of systems now under consideration (be they biological, physical, chemical, social, etc), together with the technicalities of experimentation in the real-world and the non-linear nature of system dynamics, means that computational modelling is indispensible in the pursuit of furthering our understanding of complex systems. Agent-based modelling and simulation is rapidly increasing in its popularity, in part due to the increased appreciation of the paradigm by the non-computer science community, but also due to the increase in the usability, sophistication and number of modelling frameworks that use the approach. The Flexible Large-scale Agent-based Modelling Environment (FLAME) is a relatively recent addition to the list. FLAME was designed and developed from the outset to deal with massive simulations, and to ensure that the simulation code is portable across different scales of computing and across different operating systems. In this study, we report our experiences when using FLAME to model the development and propagation of conflict within large multi-partner enterprise system implementations, which acts as an example of a complex dynamical social system. We believe FLAME is an excellent choice for experienced modellers, who will be able to fully harness the capabilities that it has to offer, and also be competent in diagnosing and solving any limitations that are encountered. Conversely, because FLAME requires considerable development of instrumentation tools, along with development of statistical analysis scripts, we believe that it is not suitable for the novice modeller, who may be better suited to using a graphical user interface driven framework until their experience with modelling and competence in programming increases.

Tissues of the upper airways of critically ill patients are particularly vulnerable to mechanical damage associated with the use of ventilators. Ventilation is known to disrupt the structural integrity of respiratory tissues and their function. This damage contributes to the vulnerability of these tissues to infection. We are currently developing tissue models of damage and infection to the upper airways. As part of our studies, we have compared how tissue storage conditions affect mechanical properties of excised respiratory tissues using a quasi-static platform. Data presented here show considerable differences in mechanical responses of stored specimens compared to freshly excised specimens. These data indicate that implementation of storage and maintenance procedures that minimize rapid degradation of tissue structure are essential for retaining the material properties in our tissue trauma models.

An exceptional tear resistance is required of the skin to protect the body from external attacks, environmental damage, and other forms of aggression. To estimate the toughness of juvenile porcine skin, we conduct two types of experiments on pre-notched specimens, placing the tissue under shear (Mode III) by using the classical trouser test with a 25 mm long pre-notch, and opening (Mode I) with an experimental setup with the same pre-notch length. We obtain two distinct average toughness values of J I I I c ≈ 20.4 k J / m 2 and J I c = 30.4 k J / m 2 , as a result of differences between these two modes of crack-tip loading and propagation, and collagen alignment. Digital image correlation coupled with single edge notch tests of 10 mm × 30 mm skin samples enables the mapping of the local strains around the tip of the crack. Effects of sample orientation and initial notch size ratio on the strain profile and on the net-section failure stress are discussed. The evaluation of the structure at the crack tip and regions undergoing more uniform states of deformation is conducted by ex situ transmission electron microscopy and in situ environmental scanning electron microscopy. Prior to crack propagation, the stress concentration is decreased by redistributing loads away from the crack tip, illustrated by gradual recruitment of collagen fibers ahead of the crack tip, thus delaying crack growth. After the crack has propagated, collagen fibers are substantially damaged, marked by delamination and recoil of the collagen fibrils.

Vesicoureteric reflux (VUR), the retrograde flow of urine from the bladder into the upper tracts, is a common finding during investigation of the urinary tract. It is a risk factor for urinary tract infection (UTI). The gold standard for diagnosis is a direct micturating cystourethrogram (MCUG). VUR may resolve spontaneously, and in recent years the trend has been towards conservative management to lower the risk of UTI. However, in some circumstances for example when conservative treatment fails, surgery may be required. Surgery for VUR is reliable at downgrading the extent of VUR, and lowers the frequency of UTI but probably does not influence the outcome of the kidneys. For this reason, patients and their families must be selected and counselled carefully. As with many surgical procedures there has been interest in minimal access although the fundamental principles of abolishing reflux remain the same. This article briefly reviews the roles of medical and surgical treatment in the management of VUR.

The field of agent-based modelling (ABM) has gained a significant following in recent years, and it is often marketed as an excellent introduction to modelling for the novice modeller or non-programmer. The typical objective of developing an agent-based model is to either increase our mechanistic understanding of a real-world system, or to predict how the dynamics of the real-world system are likely to be affected by changes to internal or external factors. Although there are some excellent ABMs that have been used in a predictive capacity across a number of domains, we believe that the promotion of ABM as an ‘accessible to all’ approach, could potentially lead to models being published that are flawed and therefore generate inaccurate predictions of real-world systems. The purpose of this article is to use our experiences in modelling complex dynamical systems, to reinforce the view that agent-based models can be useful for answering questions of the real-world domain through predictive modelling, but also to emphasise that all modellers, expert and novice alike, must make a concerted effort to adopt robust methods and techniques for constructing, validating and analysing their models, if the result is to be meaningful and grounded in the system of interest.

Elizabeth Drayson’s forensic and admirable study of the last sultan of the Nasrid Dynasty in the Emirate of Granada is a ripping tale. Her mission to rescue the ruler, Muhammad XII – or Boabdil as ...

One of the crucial issues facing enterprise modelling (EM) practices is that EM is considered technical, and rarely or never has a social focus. Social aspects referred to here are the soft aspects of the organisation that lead to organic organisation development (communication, collaboration, culture, skills and personal goals). There are many EM approaches and enterprise architecture frameworks were proposed recently. These cover different enterprise aspects, perspectives, artefacts and models with different qualities and levels of details. Yet, the imperative determination has overlaid the declarative exploration in EM as a necessity of the design effort. Rethinking the assumptions underlying EM should bring a new and different understanding on how EM can be tackled within the enterprise, in particular the joint development and optimisation of socio-technical systems. This paper discusses EM from a socio-technical systems (STS) perspective, and towards forming a new model of EM that is driven from STS theory and combined with STS practices. Then proposes a conceptual integrated model that incorporates the new concepts of STS toward building an EM framework for balanced socio-technical joint development and optimisation. The approach is illustrated in a scenario from healthcare industry. A combination between modelling and STS practices proved powerful for holistic IT modernisation, future work discussed toward the end of the paper.

Drawing on the central themes of open innovation of the knowledge inflows and outflows for a firm’s innovative achievement, this research investigates the application of external knowledge (i.e. competitor intelligence) for product innovation. We posit that open-mindedness and inter-functional coordination mediate the relationship between competitor intelligence and product innovation. We further explore the joint moderating effect of the dynamic emerging market environment on the effects of open-mindedness and inter-functional coordination on product innovation. Survey data were collected from 284 executives from Chinese IT SMEs. Analysis methods of Confirmatory Factor Analysis (CFA) and Structural Equation Modelling (SEM) are applied. Results showed that competitor intelligence has a positive and direct effect on product innovation, and their relationships can be further strengthened by the mediators—open-mindedness and inter-functional coordination. In testing the interaction with the dynamic emerging market, we found that the external environment interacts positively with open-mindedness, but negatively with inter-functional coordination on the effect on product innovation. This research enriches our understanding of external knowledge inflow for open innovation application. It contextualises the positive impact of being an open-minded and inter-functional coordinated on a firm’s product innovation. Managerial implications and future research avenues are discussed

Foundation doctors (FDs) encounter a wide range of ethical and legal issues during their first two years of work. Despite ethics being a key part of most modern undergraduate curricula, FDs can struggle with the issues they see. This study is based on results from an on-line survey answered by 479 UK FDs regarding their medical law and ethics learning needs, and their undergraduate training in this area. Over two-thirds stated they would wish to receive MEL training as an FD on self-discharge against medical advice (∼71%), sedating patients (∼70%), decision making in emergency medicine (∼67%), and withholding and withdrawing treatment (∼66%). Over half of all respondents want MEL training during their Foundation Programme on DNACPR orders (∼63%), dealing with patients with suicidal intent (∼59%), Mental Health Act (∼55%), Deprivation of Liberty Safeguards (∼54%), and end of life care (∼53%). We therefore propose a minimum curriculum for ethics and law training for FDs based on these topics, as well as cases brought by the FDs themselves.

Study Objective Children with adnexal masses might be managed by pediatric surgeons, urologists or gynecologists, with the potential for different management strategies between specialties. In this study we compared ovarian conservation rates and surgical approach for adnexal masses in children and adolescents managed either by pediatric surgeons/urologists or gynecologists at a tertiary care institution. Design Retrospective cohort review. Setting Tertiary pediatric and adult university hospital. Participants Patients younger than 18 years of age with an adnexal mass managed surgically with removal of histologically confirmed ovarian or fallopian tube tissue from 2008 to 2015. Interventions Laparoscopic or open procedure for adnexal mass. Main Outcome Measures The primary outcome was rate of ovarian conservation relative to surgical specialty. The secondary outcome was surgical approach relative to surgical specialty. Results Forty-eight patients underwent surgery for adnexal masses; 26 (54%) under pediatric surgery/urology and 22 (46%) under gynecology care. Laparoscopy was performed in 5 (19%) pediatric and 19 (86%) gynecology cases (P = .000006). Of 24 patients older than 12 years of age with a benign tumor, 10 (42%) underwent procedures resulting in loss of an ovary with or without fallopian tube; 8 of these (80%) were under pediatric care. Of the remaining 14 (58%) who underwent ovarian conserving surgery, 12 (80%) were under gynecology care (P = .0027). Conclusion Patients with a benign tumor were significantly more likely to undergo ovary-preserving surgery under gynecology care than under pediatric surgery/urology care. A multidisciplinary team approach involving gynecology and pediatric surgical specialties would be valuable in assessing the merits of ablative or conservative surgery in each case.

Late acute cellular rejection (LACR) is associated with poorer graft outcomes and non-adherence. Non-adherence to tacrolimus can be indirectly assessed by the intra-patient variability (IPV) of tacrolimus trough levels. The threshold of IPV associated with rejection is not known. We conducted a case-control study comparing 25 patients with biopsy-proven LACR against 25 stable controls matched for age group, primary diagnosis and time post-transplant. IPV was calculated using coefficient of variance (CV) and mean absolute deviation (MAD) using tacrolimus levels in the preceding 12 months. We also assessed the percentage time for tacrolimus levels

Aims: Renovascular hypertension is a rare cause of paediatric hypertension. It is however, a potentially treatable cause particularly when caused by renal artery stenosis (RAS). Materials and Methods: We present the case of an 11-month-old girl presenting with cardiac dysfunction. She was found to be hypertensive with a systolic blood pressure >180mmHg. DMSA demonstrated a small right kidney and a divided renal function of 6% on the right and 94% on the left. Spectral analysis demonstrated abnormal waveforms suggestive of RAS of the left kidney. Results: Angioplasty with a cutting balloon was successful. Blood pressure measurements, renal function and left ventricular function improved. Conclusion: RAS can be successfully treated with cutting balloon angioplasty after failure of convention balloon angioplasty to relieve the narrowing. In our case, there was an immediate successful angiographic result that on mid-term follow-up demonstrated significant improvement in clinical and biochemical outcomes and cessation of all anti-hypertensive medication.

The landscape of transition is complex and variable. There is variability at the level of individuals (whose transition needs may be quite different), at the level of service provision, and in the type of health and social care system. The ability to understand and measure these variables in the process of transition, and how that may relate to the outcome for individuals is important. Such metrics will begin to inform how best to tackle complexity and variation in all these areas. The direction of travel for many adults with long term childhood conditions is largely unknown.

Improved bladder and renal management benefit patients with congenital uropathy and congenital pediatric kidney disease. This may translate to delayed initial renal transplantation in these patients, and improved graft and patient survival. Our primary study purpose was to determine whether patients with congenital uropathy and congenital pediatric kidney disease have demonstrated later time to first transplantation and/or graft survival.SRTR (Scientific Registry of Transplant Recipients) was analyzed for first renal transplant and survival data in patients with congenital uropathy and congenital pediatric kidney disease from 1996 to 2012. Congenital uropathy included chronic pyelonephritis/reflux, prune belly syndrome and congenital obstructive uropathy. Congenital pediatric kidney disease included polycystic kidney disease, hypoplasia, dysplasia, dysgenesis, agenesis and familial nephropathy.A total of 7,088 patients with congenital uropathy and 24,315 with congenital pediatric kidney disease received a first renal transplant from 1996 to 2012. A significant shift was seen in both groups toward older age at initial renal transplantation in those 18 through 64 years old. In the congenital uropathy group this effect was most facilitated by decreased renal transplantion in patients between 18 and 35 years old (38% in 1996 vs 26% in 2012). The congenital pediatric kidney disease group showed a substantial decrease in patients who were 35 to 49 years old (from 39% to 29%). At 10-year followup the congenital uropathy group showed better graft and patient survival than the congenital pediatric kidney disease group. However, aged matched comparison revealed comparable survival rates in the 2 groups.Analysis of trends in the last 14 years demonstrated that patients with both lower and upper tract congenital anomalies experienced delayed time to the first renal transplant. Furthermore, patients had similar age matched graft and patient survival whether the primary source of renal demise was the congenital lower or upper tract. These findings may indicate that improved urological and nephrological care are promoting renal preservation in both groups.

There is increasing interest in the role of the glycosylphosphatidylinositol (GPI) anchor attached to the cellular prion protein (PrP(C)). Since GPI anchors can alter protein targeting, trafficking and cell signaling, our recent study examined how the structure of the GPI anchor affected prion formation. PrP(C) containing a GPI anchor from which the sialic acid had been removed (desialylated PrP(C)) was not converted to PrP(Sc) in prion-infected neuronal cell lines and in scrapie-infected primary cortical neurons. In uninfected neurons desialylated PrP(C) was associated with greater concentrations of gangliosides and cholesterol than PrP(C). In addition, the targeting of desialylated PrP(C) to lipid rafts showed greater resistance to cholesterol depletion than PrP(C). The presence of desialylated PrP(C) caused the dissociation of cytoplasmic phospholipase A2 (cPLA2) from PrP-containing lipid rafts, reduced the activation of cPLA2 and inhibited PrP(Sc) production. We conclude that the sialic acid moiety of the GPI attached to PrP(C) modifies local membrane microenvironments that are important in PrP-mediated cell signaling and PrP(Sc) formation.

This paper investigates the medical law and ethics (MEL) learning needs of Foundation doctors (FYs) by means of a national survey developed in association with key stakeholders including the General Medical Council and Health Education England. Four hundred sevnty-nine doctors completed the survey. The average self-reported level of preparation in MEL was 63%. When asked to rate how confident they felt in approaching three cases of increasing ethical complexity, more FYs were fully confident in the more complex cases than in the more standard case. There was no apparent relationship with confidence and reported teaching at medical school. The less confident doctors were no more likely to ask for further teaching on the topic than the confident doctors. This suggests that FYs can be vulnerable when facing ethical decisions by being underprepared, not recognising their lack of ability to make a reasoned decision or by being overconfident. Educators need to be aware of this and provide practical MEL training based on trainee experiences and real-world ethics and challenge learners’ views. Given the complexities of many ethical decisions, preparedness should not be seen as the ability to make a difficult decision but rather a recognition that such cases are difficult, that doubt is permissible and the solution may well be beyond the relatively inexperienced doctor. Educators and supervisors should therefore be ensuring that this is clear to their trainees. This necessitates an environment in which questions can be asked and uncertainty raised with the expectation of a supportive response.

Health and social care professionals are required to work together to deliver person-centered care. Professionals therefore find themselves making decisions within multidisciplinary teams. For educators, there has been a call to bring students from differing professions together to learn to enable more effective teamwork, interprofessional communication, and collaborative practice. This multidisciplinary working is complicated by the increasingly complex nature of ethical dilemmas that health and social care professionals face. It is therefore widely recognized that the teaching and learning of ethics within health and social care courses is valuable. In this paper, we briefly make the case in support of teaching and learning health and social care ethics through the medium of interprofessional education (IPE). The purpose of this paper is to provide guidance to educators intending to design ethics-orientated IPE for health and social care students. The guidance is based on the ongoing experiences of designing and implementing ethics-orientated IPE across five departments within two universities located in the North of England over a five-year period. Descriptions of the ethics-orientated IPE activities are included in the guide, along with key resources recommended.

Skin, the outermost layer of the body, fulfills a broad range of functions, protecting internal organs from damage and infection, while regulating the body's temperature and water content via the exchange of heat and fluids. It must be able to withstand and recover from extensive deformation and damage that can occur during growth, movement, and potential injuries. A detailed investigation of the evolution of the collagen architecture of the dermis as a function of deformation is conducted, which reveals new aspects that help us to understand the mechanical response of skin. Juvenile pig is used as a model material because of its similarity to human skin. The dermis is found to have a tridimensional woven structure of collagen fibers, which evolves with deformation. After failure, we observe that the fibers have straightened and aligned in the direction of tension. The effects of strain-rate change, cyclic loading, stress relaxation, and orientation are quantitatively established. Digital image correlation techniques are implemented to quantify skin's anisotropy; measurements of the Poisson ratio are reported. This is coupled with transmission electron microscopy which enables obtaining quantitative strain parameters evaluated through the orientation and curvature of the collagen fibers and their changes, for the first time in all three dimensions of the tissue. A model experiment using braided human hair in tension exhibits a similar J-curve response to skin, and we propose that this fiber configuration is at least partially responsible for the monotonic increase of the tangent modulus of skin with strain. The obtained results are intended to serve as a basis for structurally-based models of skin. STATEMENT OF SIGNIFICANCE: Our study reveals a new aspect of the dermis: it is comprised of a tridimensional woven structure of collagen fibers, which evolves with deformation. This is enabled by primarily two techniques, transmission electron microscopy on three perpendicular planes and confocal images with second harmonic generation fluorescence of collagen, captured at different intervals of depth. After failure, the fibers have straightened and aligned in the direction of tension. Digital image correlation techniques are implemented to quantify skin's anisotropy; measurements of the Poisson ratio are reported. A model experiment using braided human hair in tension exhibits a similar J-curve response to skin, and we propose that this fiber configuration is at least partially responsible for the monotonic increase of the tangent modulus of skin with strain.

Objective Despite poor clinic communication and staff treatment being reported by donors, high rates of overall satisfaction are still reported in surveys. This study will evaluate the importance of communication and interaction between donors and fertility clinic staff in gamete donor care. Methods We report on 120 egg and sperm donors’ responses to a UK-wide online satisfaction survey. The survey focused on donors’ interactions with fertility clinic staff pre-, during, and post- donation. Basic cross-tabulation was performed on the data using online survey software. Textual data was read and extracts identified, which illustrated and expanded on the findings from the numerical data. Diagrammatic modeling was also utilised to analyse the textual data, with particular focus to relationships between the donors and clinic staff, the main activities within the gamete donation process, and how these activities may affect donor satisfaction with the gamete donation process. Results Donors expressed concern for the infertile couple and the resulting child; conveyed frustration at not receiving information on the expenses they could claim; felt lost in the system regarding the ease of making clinic appointments, and once made they were routinely not seen on time for these appointments. Donors also negatively commented on aftercare, the location and condition of the donation room, and information on contraception. In addition, Ovarian Hyperstimulation Syndrome was frequently reported, with these egg donors believing that clinic staff were not concerned with their physical or emotional well-being, but were instead disproportionately focused on extracting the eggs. Conclusions The multifaceted notion of donors highlights the complexity inherent to the gamete donation process, which comprises various aspects of uncertainty in the donation system, and ambiguity in the donation process. Categorising donors as Altruist, Customer, and Patient, conveys the particular importance of staff communication and treatment in donor care. These categories are not mutually exclusive however, in that an individual donor may experience more than one of these perspectives during the course of their gamete donation journey. Finally, there were a number of exemplar cases, where donors reported high satisfaction throughout, and these correlated with them being given a single point of contact at the clinic. Subject to resource constraints, we suggest that this practice should be implemented throughout clinics in the UK, so that donors have access to dedicated clinic staff who not only support them emotionally and physically throughout the gamete donation process, but also ensure that communication is open, clear, timely, and consistent.