Importance and vulnerability of the world's water towers.

Mountains are the water towers of the world, supplying a substantial part of both natural and anthropogenic water demands1,2. They are highly sensitive and prone to climate change3,4, yet their importance and vulnerability have not been quantified at the global scale. Here we present a global water tower index (WTI), which ranks all water towers in terms of their water-supplying role and the downstream dependence of ecosystems and society. For each water tower, we assess its vulnerability related to water stress, governance, hydropolitical tension and future climatic and socio-economic changes. We conclude that the most important (highest WTI) water towers are also among the most vulnerable, and that climatic and socio-economic changes will affect them profoundly. This could negatively impact 1.9 billion people living in (0.3 billion) or directly downstream of (1.6 billion) mountainous areas. Immediate action is required to safeguard the future of the world's most important and vulnerable water towers.

Germline-focused analysis of tumour-detected variants in 49,264 cancer patients: ESMO Precision Medicine Working Group recommendations.

BACKGROUND: The European Society for Medical Oncology Precision Medicine Working Group (ESMO PMWG) was reconvened to update its 2018/19 recommendations on follow-up of putative germline variants detected on tumour-only sequencing, which were based on an analysis of 17 152 cancers. METHODS: We analysed an expanded dataset including 49 264 paired tumour-normal samples. We applied filters to tumour-detected variants based on variant allele frequency, predicted pathogenicity and population variant frequency. For 58 cancer-susceptibility genes, we then examined the proportion of filtered tumour-detected variants of true germline origin [germline conversion rate (GCR)]. We conducted subanalyses based on the age of cancer diagnosis, specific tumour types and 'on-tumour' status (established tumour-gene association). RESULTS: Analysis of 45 472 nonhypermutated solid malignancy tumour samples yielded 21 351 filtered tumour-detected variants of which 3515 were of true germline origin. 3.1% of true germline pathogenic variants were absent from the filtered tumour-detected variants. For genes such as BRCA1, BRCA2 and PALB2, the GCR in filtered tumour-detected variants was >80%; conversely for TP53, APC and STK11 this GCR was <2%. CONCLUSION: Strategic germline-focused analysis can prioritise a subset of tumour-detected variants for which germline follow-up will produce the highest yield of most actionable true germline variants. We present updated recommendations around germline follow-up of tumour-only sequencing including (i) revision to 5% for the minimum per-gene GCR, (ii) inclusion of actionable intermediate penetrance genes ATM and CHEK2, (iii) definition of a set of seven 'most actionable' cancer-susceptibility genes (BRCA1, BRCA2, PALB2, MLH1, MSH2, MSH6 and RET) in which germline follow-up is recommended regardless of tumour type.

The value of allied health professional research engagement on healthcare performance: a systematic review.

BACKGROUND: Existing evidence suggests that clinician and organisation engagement in research can improve healthcare performance. With the increase in allied health professional (AHP) research activity, it is imperative for healthcare organisations, clinicians, managers, and leaders to understand research engagement specifically within allied health fields. This systematic review aims to examine the value of research engagement by allied health professionals and organisations on healthcare performance. METHODS: This systematic review had a two-stage search strategy. Firstly, the papers from a previous systematic review examining the effect of research engagement in healthcare were screened to identify papers published pre-2012. Secondly, a multi-database search was used to conduct a re-focused update of the previous review, focusing specifically on allied health to identify publications from 2012-2021. Studies which examined the value of allied health research engagement on healthcare performance were included. All stages of the review were conducted by two reviewers independently. Each study was assessed using the appropriate Joanna Briggs Institute critical appraisal tool. A narrative synthesis was completed to analyse the similarities and differences between and within the different study types. RESULTS: Twenty-two studies were included, comprising of mixed research designs, of which six were ranked as high importance. The findings indicated that AHP research engagement appears related to positive findings in improvements to processes of care. The review also identified the most common mechanisms which may link research engagement with these improvements. DISCUSSION: This landmark systematic review and narrative synthesis suggests value in AHP research engagement in terms of both processes of care and more tentatively, of healthcare outcomes. While caution is required because of the lack of robust research studies, overall the findings support the agenda for growing AHP research. Recommendations are made to improve transparent reporting of AHP research engagement and to contribute essential evidence of the value of AHP research engagement. TRIAL REGISTRATION: This systematic review protocol was registered with the international prospective register of systematic reviews, PROSPERO (registration number CRD42021253461 ).

Comparison between Clinical Profile and Outcome of Patients Admitted with Moderate and Severe COVID-19 Illness in the First and Second Wave of COVID-19 in a Tertiary Care Centre in South India.

Background: SARS-coronavirus-2 has caused large number of infections globally. The infections have presented in a wave form in most of the countries. There have been differences in the clinical presentation, course, and the outcomes in the different waves. Aim: This study describes the clinical features and course of the patients admitted with COVID-19 illness between the first and second wave of COVID-19 in a tertiary care center in South India. Materials and Methods: This was a cross-sectional study where case record analysis of the patients admitted with moderate and severe COVID-19 illness in a tertiary care center in South India was performed. Patients admitted between August 1, 2020, and November 30, 2020, were considered to be affected in the first wave and those admitted between April 30, 2021, and July 30, 2021, were considered to be in the second wave of COVID-19. First wave and second wave periods were determined by a steep surge in infections in India as per the epidemiological data. The symptoms, comorbidities, clinical profile, severity, laboratory parameters, need for assisted ventilation, medications used, and outcome were compared between the two-time frames. Results: A total of 123 patients' data were analyzed in each wave. 72 (58%) patients had fever, while 64 (52%) patients had fever in COVID second wave. In the first wave, five (4%) patients had diarrhea, and four (3.2%) patients had vomiting, whereas in second wave, 43 (34%) patients had diarrhea, and 25 (20 percent) patients had vomiting (P < 0.001). It was seen in the present study that more number of patients in the age group of 31 to 40 years had more serious illness and adverse outcomes in second wave compared with patients in first wave where age group of 51-60 years was more seriously affected. In COVID first wave, 80 (65.0%) were having moderate COVID-19 illness and 43 (35%) had severe illness. In the second wave, 70 (57%) had moderate illness and 53 (43%) patients had severe illness. In the first wave, 31 patients (25%) required non-invasive ventilation (NIV), whereas 79 patients (64%) required NIV in second wave (P < 0.001). First wave resulted in 12 (9.7%) deaths, whereas second wave resulted in 20 (16.2%) deaths. Conclusion: The patients with COVID-19 illness in the second wave presented with more non-respiratory symptoms like vomiting, diarrhea, and joint pains. The patients who had severe illness in the second wave were comparatively younger than the patients of the first wave. The requirement of ventilatory support and immunosuppressants was more in the second wave.

Correlation of fetal ventricular size and need for postnatal cerebrospinal fluid diversion surgery in open spina bifida.

OBJECTIVES: Open spina bifida is a common cause of hydrocephalus in the postnatal period. In-utero closure of the fetal spinal defect decreases the need for postnatal cerebrospinal fluid (CSF) diversion surgery. Good prenatal predictors of the need for postnatal CSF diversion surgery are currently lacking. In this study, we aimed to assess the association of fetal ventriculomegaly and its progression over the course of pregnancy with the rate of postnatal hydrocephalus requiring intervention. METHODS: In this retrospective study, fetuses with a prenatal diagnosis of open spina bifida were assessed longitudinally. Ventricular diameter, as well as other potential predictors of the need for postnatal CSF diversion surgery, were compared between fetuses undergoing prenatal closure and those undergoing postnatal repair. RESULTS: The diameter of the lateral ventricle increased significantly throughout gestation in both groups, but there was no difference in maximum ventricular diameter at first or last assessment between fetuses undergoing prenatal closure and those undergoing postnatal repair. There was no significant difference in the rate of progression of ventriculomegaly between the two groups, with a mean progression rate of 0.83 ± 0.5 mm/week in the prenatal-repair group and 0.6 ± 0.6 mm/week in the postnatal-repair group (P = 0.098). Fetal repair of open spina bifida was associated with a lower rate of postnatal CSF diversion surgery (P < 0.001). In all subjects, regardless of whether they had prenatal or postnatal surgery, the severity of ventriculomegaly at first and last assessments was associated independently with the need for postnatal CSF diversion surgery (P = 0.005 and P = 0.001, respectively), with a greater need for surgery in fetuses with larger ventricular size, even after controlling for gestational age at assessment. CONCLUSIONS: In fetuses with open spina bifida, fetal ventricular size increases regardless of whether spina bifida closure is performed prenatally or postnatally, but the need for CSF diversion surgery is significantly lower in those undergoing prenatal repair. Ventriculomegaly is associated independently with the need for postnatal CSF diversion in fetuses with open spina bifida, irrespective of timing of closure. © 2021 International Society of Ultrasound in Obstetrics and Gynecology.

TROPHY registry - status report.

INTRODUCTION: The TROPHY registry has been established to conduct an international multicenter prospective data collection on the surgical management of neonatal intraventricular hemorrhage (IVH)-related hydrocephalus to possibly contribute to future guidelines. The registry allows comparing the techniques established to treat hydrocephalus, such as external ventricular drainage (EVD), ventricular access device (VAD), ventricular subgaleal shunt (VSGS), and neuroendoscopic lavage (NEL). This first status report of the registry presents the results of the standard of care survey of participating centers assessed upon online registration. METHODS: On the standard of treatment forms, each center indicated the institutional protocol of interventions performed for neonatal post-hemorrhagic hydrocephalus (nPHH) for a time period of 2 years (Y1 and Y2) before starting the active participation in the registry. In addition, the amount of patients enrolled so far and allocated to a treatment approach are reported. RESULTS: According to the standard of treatment forms completed by 56 registered centers, fewer EVDs (Y1 55% Y2 46%) were used while more centers have implemented NEL (Y1 39%; Y2 52%) to treat nPHH. VAD (Y1 66%; Y2 66%) and VSGS (Y1 42%; Y2 41%) were used at a consistent rate during the 2 years. The majority of the centers used at least two different techniques to treat nPHH (43%), while 27% used only one technique, 21% used three, and 7% used even four different techniques. Patient data of 110 infants treated surgically between 9/2018 and 2/2021 (13% EVD, 15% VAD, 30% VSGS, and 43% NEL) were contributed by 29 centers. CONCLUSIONS: Our results emphasize the varying strategies used for the treatment of nPHH. The international TROPHY registry has entered into a phase of growing patient recruitment. Further evaluation will be performed and published according to the registry protocol.

Non-immune fetal hydrops: etiology and outcome according to gestational age at diagnosis.

OBJECTIVE: Fetal hydrops is associated with increased perinatal morbidity and mortality. The etiology and outcome of fetal hydrops may differ according to the gestational age at diagnosis. The aim of this study was to evaluate the cause, evolution and outcome of non-immune fetal hydrops (NIFH), according to the gestational age at diagnosis. METHODS: This was a retrospective cohort study of all singleton pregnancies complicated by NIFH, at the Fetal Medicine Unit at St George's University Hospital, London, UK, between 2000 and 2018. All fetuses had detailed anomaly and cardiac ultrasound scans, karyotyping and infection screening. Prenatal diagnostic and therapeutic intervention, gestational age at diagnosis and delivery, as well as pregnancy outcome, were recorded. Regression analysis was used to test for potential association between possible risk factors and perinatal mortality. RESULTS: We included 273 fetuses with NIFH. The etiology of the condition varied significantly in the three trimesters. Excluding 30 women who declined invasive testing, the cause of NIFH was defined as unknown in 62 of the remaining 243 cases (25.5%). Chromosomal aneuploidy was the most common cause of NIFH in the first trimester. It continued to be a significant etiologic factor in the second trimester, along with congenital infection. In the third trimester, the most common etiology was cardiovascular abnormality. Among the 152 (55.7%) women continuing the pregnancy, 48 (31.6%) underwent fetal intervention, including the insertion of pleuroamniotic shunts, fetal blood transfusion and thoracentesis. Fetal intervention was associated significantly with lower perinatal mortality (odds ratio (OR), 0.30 (95% CI, 0.14-0.61); P < 0.001); this association remained significant after excluding cases with a diagnosis of anemia or infection (OR, 0.29 (95% CI, 0.13-0.66); P = 0.003). In 104 fetuses not undergoing active fetal intervention, the gestational age at diagnosis was the only parameter that was significantly associated with the risk of perinatal mortality (OR, 0.92 (95% CI, 0.85-0.99); P = 0.035), while the affected body cavity and polyhydramnios were not (P > 0.05). CONCLUSIONS: An earlier gestational age at diagnosis of NIFH was associated with an increased risk of aneuploidy and worse pregnancy outcome, including a higher risk of perinatal loss. Fetal therapy was associated significantly with lower perinatal mortality. © 2020 Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

State-wide utilization and performance of traditional and cell-free DNA-based prenatal testing pathways: the Victorian Perinatal Record Linkage (PeRL) study.

OBJECTIVES: To perform individual record linkage of women undergoing screening with cell-free DNA (cfDNA), combined first-trimester screening (CFTS), second-trimester serum screening (STSS), and/or prenatal and postnatal cytogenetic testing with the aim to (1) obtain population-based estimates of utilization of prenatal screening and invasive diagnosis, (2) analyze the performance of different prenatal screening strategies, and (3) report the residual risk of any major chromosomal abnormality following a low-risk aneuploidy screening result. METHODS: This was a retrospective study of women residing in the state of Victoria, Australia, who underwent prenatal screening or invasive prenatal diagnosis in 2015. Patient-funded cfDNA referrals from multiple providers were merged with state-wide results for government-subsidized CFTS, STSS and invasive diagnostic procedures. Postnatal cytogenetic results from products of conception and infants up to 12 months of age were obtained to ascertain cases of false-negative screening results and atypical chromosomal abnormalities. Individual record linkage was performed using LinkageWizTM . RESULTS: During the study period, there were 79 140 births and 66 166 (83.6%) women underwent at least one form of aneuploidy screening. Linkage data were complete for 93.5% (n = 61 877) of women who underwent screening, and of these, 73.2% (n = 45 275) had CFTS alone, 20.2% (n = 12 486) had cfDNA alone; 5.3% (n = 3268) had STSS alone, 1.3% (n = 813) had both CFTS and cfDNA, and < 0.1% (n = 35) had both STSS and cfDNA. CFTS had a combined sensitivity for trisomies 21 (T21), 18 (T18) and 13 (T13) of 89.57% (95% CI, 82.64-93.93%) for a screen-positive rate (SPR) of 2.94%. There were 12 false-negative results in the CFTS pathway, comprising 10 cases of T21, one of T18 and one of T13. cfDNA had a combined sensitivity for T21, T18 and T13 of 100% (95% CI, 95.00-100%) for a SPR of 1.21%. When high-risk cfDNA results for any chromosome (including the sex chromosomes) and failed cfDNA tests were treated as screen positives, the SPR for cfDNA increased to 2.42%. The risk of any major chromosomal abnormality (including atypical abnormalities) detected on prenatal or postnatal diagnostic testing after a low-risk screening result was 1 in 1188 for CFTS (n = 37) and 1 in 762 for cfDNA (n = 16) (P = 0.13). The range of chromosomal abnormalities detected after a low-risk cfDNA result included pathogenic copy-number variants (n = 6), triploidy (n = 3), rare autosomal trisomies (n = 3) and monosomy X (n = 2). CONCLUSIONS: Our state-wide record-linkage analysis delineated the utilization and clinical performance of the multitude of prenatal screening pathways available to pregnant women. The sensitivity of cfDNA for T21, T18 and T13 was clearly superior to that of CFTS. While there was no statistically significant difference in the residual risk of any major chromosomal abnormality after a low-risk CFTS or cfDNA result, there were fewer live infants diagnosed with a major chromosomal abnormality in the cfDNA cohort. These data provide valuable population-based evidence to inform practice recommendations and health policies. Copyright © 2019 ISUOG. Published by John Wiley & Sons Ltd.

Germline-focussed analysis of tumour-only sequencing: recommendations from the ESMO Precision Medicine Working Group.

It is increasingly common in oncology practice to perform tumour sequencing using large cancer panels. For pathogenic sequence variants in cancer susceptibility genes identified on tumour-only sequencing, it is often unclear whether they are of somatic or constitutional (germline) origin. There is wide-spread disparity regarding both the extent to which systematic 'germline-focussed analysis' is carried out upon tumour sequencing data and for which variants follow-up analysis of a germline sample is carried out. Here we present analyses of paired sequencing data from 17 152 cancer samples, in which 1494 pathogenic sequence variants were identified across 65 cancer susceptibility genes. From these analyses, the European Society of Medical Oncology Precision Medicine Working Group Germline Subgroup has generated (i) recommendations regarding germline-focussed analyses of tumour-only sequencing data, (ii) indications for germline follow-up testing and (iii) guidance on patient information-giving and consent.

Clinical and economic impact of school-based nonavalent human papillomavirus vaccine on women in Singapore: a transmission dynamic mathematical model analysis.

OBJECTIVE: To examine the epidemiological and economic impact of a nine-valent (nonavalent) human papillomavirus (HPV) 6/11/16/18/31/33/45/52/58 vaccine programme for young teenagers in Singapore. DESIGN: Mathematical modelling. SETTING: Pharmaco-economic simulation projection. POPULATION: Singapore demography. METHODS: Clinical, epidemiological and financial data from Singapore were used in a validated HPV transmission dynamic mathematical model to analyse the impact of nonavalent HPV vaccination over quadrivalent and bivalent vaccines in a school-based 2-dose vaccination for 11- to 12-year-old girls in the country. The model assumed routine cytology screening in the current rate (50%) and vaccine coverage rate of 80%. MAIN OUTCOME MEASURES: Changes over a 100-year time period in the incidence and mortality rates of cervical cancer, case load of genital warts, and incremental cost-effectiveness ratio (ICER). RESULTS: Compared with bivalent and quadrivalent HPV vaccination programmes, nonavalent HPV universal vaccination resulted in an additional reduction of HPV31/33/45/52/58 related CIN1 of 40.5%, CIN 2/3 of 35.4%, cervical cancer of 23.5%, and cervical cancer mortality of 20.2%. Compared with bivalent HPV vaccination, there was an additional reduction in HPV-6/11 related CIN1 of 75.7%, and genital warts of 78.9% in women and 73.4% in men. Over the 100 years, after applying a discount of 3%, disease management cost will be reduced by 32.5% (versus bivalent) and 7.5% (versus quadrivalent). The incremental cost-effectiveness ratio (ICER) per quality-adjusted life-year gained was SGD 929 compared with bivalent vaccination and SGD 9864 compared with quadrivalent vaccination. CONCLUSION: Universal two-dose nonavalent HPV vaccination for 11- to 12-year-old adolescent women is very cost-effective in Singapore. TWEETABLE ABSTRACT: Nonavalent HPV vaccination of 11- to 12-year-old girls is cost-effective in Singapore.

The clinical utility of genetic testing of tissues from pregnancy losses.

OBJECTIVE: To map the current testing being undertaken following pregnancy loss across the UK and to examine the clinical utility in terms of identifying a cause for the loss and in identifying couples at risk of an unbalanced liveborn child. DESIGN: Retrospective audit. SETTING: UK, for the year 2014. POPULATION: An audit of 6465 referrals for genetic testing of tissue samples following pregnancy loss. METHODS: Data were obtained by questionnaire from 15 UK regional genetics laboratories. MAIN OUTCOME MEASURES: Data were analysed with respect to gestational age, the presence of identified fetal anomalies, methodologies used, abnormality rates and the presence of a parental balanced rearrangement. RESULTS: Of 6465 referrals a genetic cause was identified in 22% of cases (before 12 weeks' gestation, in 47%; at 12-24 weeks, in 14%; after 24 weeks, in 6%). In 0.4% of cases a balanced parental rearrangement was identified where there was a risk of an affected liveborn child in a future pregnancy. Eighty percent of genetic imbalances identified were aneuploidy or triploidy and could be identified by quantitative fluorescence polymerase chain reaction alone. There was significant variation across the UK in acceptance criteria, testing strategies and thus level of resolution of testing. CONCLUSIONS: Genetic testing of tissues following pregnancy loss identifies a probable cause of fetal demise in 22% of cases, but it is of low clinical utility in identifying couples at risk of a future unbalanced liveborn child. A comprehensive multidisciplinary review is needed to develop proposals for an affordable and equitable service. TWEETABLE ABSTRACT: UK audit of genetic testing of fetal loss shows variation in access to and resolution of analysis.

A Study of Microalbuminuria (MAU) and Advanced Glycation End Products (AGEs) Levels in Diabetic and Hypertensive Subjects.

The prevalence of non-communicable diseases like diabetes mellitus (DM) and hypertension (HTN) is growing worldwide. Both lead to nephropathy if not controlled effectively. Microalbuminuria (MAU) is recognized as an early predictor for nephropathy. Additionally, the timely detection of advanced glycation end products (AGEs) is also considered to be an important prognostic factor for diabetic nephropathies. Hence, screening for the early detection of MAU and AGEs would be an useful and relatively inexpensive laboratory test for early clinical diagnosis for the incidence of nephropathy in these diseases. This study was conducted in DM, HTN and pregnancy induced hypertensive (PIH) subjects. MAU and Nε-Carboxymethyllysine (CML) levels were estimated by in-house RIA kits in the patient groups and controls, while the total AGEs level in serum was determined by ELISA. The levels of MAU, CML and AGE-BSA were observed to be significantly higher in DM, HTN and PIH subjects compared to controls (p < 0.001). Increased serum CML and AGEs levels in DM, HTN and PIH subjects indicated ongoing glycemic damage and their susceptibility to develop renal complications.

Fetal myocardial deformation in maternal diabetes mellitus and obesity.

OBJECTIVE: Experimental evidence suggests that changes in the fetal myocardium result from intrauterine effects of maternal diabetes mellitus and obesity. The aim of this study was to assess fetal cardiac function using two-dimensional speckle-tracking echocardiography to determine the effects of maternal diabetes and obesity on the fetal myocardium. METHODS: Comparative cross-sectional evaluation of myocardial function in fetuses of mothers with diabetes mellitus (FDM) or obesity (FO) and normal gestational age-matched control fetuses (FC) was performed using two-dimensional speckle-tracking echocardiography at two centers. RESULTS: In total, 178 fetuses (82 FDM, 26 FO and 70 FC) met the enrolment criteria. Mean gestational age at assessment was similar among groups: 25.3 ± 5.1 weeks for FDM, 25.0 ± 4.6 weeks for FO and 25.1 ± 4.9 weeks for FC. Mean maternal body mass index was significantly higher in FDM and FO groups compared with the FC group. Statistically significant differences in fetal cardiac function were detected between FDM and FC for global longitudinal strain (mean ± SD, -21.4 ± 6.5% vs -27.0 ± 5.2%; P < 0.001), global circumferential strain (mean ± SD, -22.6 ± 6.5% vs -26.2 ± 6.8%; P = 0.002), average longitudinal systolic strain rate (median, -1.4 (interquartile range (IQR), -1.7 to -1.1)/s vs -1.6 (IQR, -2.0 to -1.4)/s; P = 0.001) and average circumferential systolic strain rate (median, -1.4 (IQR, -1.9 to -1.1)/s vs -1.6 (IQR, -2.1 to -1.3)/s; P = 0.006). Cases of non-obese FDM also had abnormal strain parameters compared with FC. Global longitudinal strain (mean ± SD, -21.1 ± 7.5%) and average circumferential systolic strain rate (median, -1.3 (IQR, -1.8 to -1.1)/s) were significantly lower in FO compared with FC. CONCLUSIONS: Unfavorable changes occur in the fetal myocardium in response to both maternal diabetes mellitus and obesity. The long-term prognostic implications of these changes require further study. Copyright © 2016 ISUOG. Published by John Wiley & Sons Ltd.

Cyclin-dependent kinase 5 is required for normal cerebellar development.

Cyclin-dependent kinase 5 (Cdk5) is a serine/threonine kinase, and its kinase activity is dependent upon its association with either of the activating subunits p35 or p39, which are mainly expressed in neurons. We previously reported that Cdk5 knockout (KO) mice exhibit perinatal lethality, defective neuronal migration, and abnormal positioning of neurons in the facial motor nucleus and inferior olive in the hindbrain and Purkinje cells (PCs) in the cerebellum. In this study, we focused on the analysis of the role of Cdk5 in cerebellar development. For this purpose we generated midbrain-hindbrain-specific Cdk5 conditional knockout (MHB-Cdk5 KO) mice because the cerebellum develops postnatally, whereas Cdk5 KO mice die perinatally. Histological analysis of the MHB-Cdk5 KO mice revealed a significant size reduction of the cerebellum. In addition, profound disturbance of inward migration of granule cells (GC) was observed in the developing cerebellum. A normal dendritic development of the Purkinje cells (PCs) was disturbed in MHB-Cdk5 KO mice. Cultured Cdk5-null PCs showed similar dendritic abnormalities. These results indicate that Cdk5/p35 plays an important role in neuronal migration of PCs and GCs and dendrite formation of PCs in cerebellar development.

Thoracoscopic and endovascular management of retained haemothoarx associated with an intercostal artery pseudoaneurysm.

Intercostal artery pseudoaneurysm (IAP) is a rare entity and may complicate a percutaneous intervention through an intercostal space or follow thoracic trauma. Its rupture into the pleural space can give rise to haemothorax, which if untreated may lead to a retained haemothorax (RH). Traditionally both the IAP and the RH are managed by a thoracotomy. We report a patient who developed an IAP with haemothorax following a trauma. The diagnosis was established by computed tomography. The patient was treated by endovascular embolisation of the IAP followed by thoracoscopic decortications of the RH.

Understanding osteoporosis and fractures: an introduction to the use of qualitative research.

BACKGROUND: Qualitative research has been recognized in recent years as a field of inquiry used to understand people's beliefs, attitudes, behaviors, culture or lifestyle. While quantitative results are challenging to apply in everyday practice, the qualitative paradigm can be useful to fill in a research context that is poorly understood or ill-defined. It can provide an in-depth study of interactions, a way to incorporate context, and a means to hear the voices of participants. Understanding experiences, motivation, and beliefs can have a profound effect on the interpretation of quantitative research and generating hypotheses. In this paper, we will review different qualitative approaches that healthcare providers and researchers may find useful to implement in future study designs, specifically in the context of osteoporosis and fracture. METHODS: We will provide insight into the qualitative paradigm gained from the osteoporosis literature on fractures using examples from the database Scopus. Five prominent qualitative techniques (narratives, phenomenology, grounded theory, ethnography, and case study) can be used to generate meanings of the social and clinical world. DISCUSSION AND CONCLUSION: We have highlighted how these strategies are implemented in qualitative research on osteoporosis and fractures and are anchored to specific methodological practices. We focus on studies that explore patient psychosocial experiences of diagnosis and treatment, cultural boundaries, and interprofessional communication. After reviewing the research, we believe that action research, that is not frequently used, could also effectively be used by many professions to improve programs and policies affecting those dealing with osteoporosis issues.