The impacts of a global pandemic on the efficacy and stability of contemporary wildlife conservation: South Africa as a case study.

Conservationists speculated on potential benefits to wildlife of lockdown restrictions because of the COVID-19 pandemic but voiced concern that restrictions impeded nature conservation. We assessed the effects of lockdown restrictions on biodiversity conservation in South Africa, a biodiverse country with economic inequality and reliance on wildlife resources. We solicited expert opinion using the IUCN's Threats Classification Scheme to structure a questionnaire and illustrated responses with individual case studies from government parastatal and non-governmental conservation organisations. The most highly reported threats were biological resource use, residential/commercial developments, invasive species, and human intrusions. The trends reported by 90 survey respondents were supported by case studies using environmental compliance data from parastatal conservation organisations. Lack of tourism revenue and funding were cited as hindrances to conservation. Mechanisms to prevent environmental degradation in the face of global emergencies must be implemented and 'ring-fenced' to ensure conservation is not a casualty during future global crises.

Dystrophic calcinosis cutis successfully treated with extracorporeal shockwave lithotripsy.

This case illustrates a presentation with dystrophic calcinosis cutis recalcitrant to several treatment modalities. Treatment with extracorporeal shockwave lithotripsy was initiated with near complete resolution of calcium deposits.

Radiotherapy, immunotherapy, and the tumour microenvironment: Turning an immunosuppressive milieu into a therapeutic opportunity.

Immune checkpoint blockade (ICB) has revolutionised the treatment of solid tumours, yet most patients do not derive a clinical benefit. Resistance to ICB is often contingent on the tumour microenvironment (TME) and modulating aspects of this immunosuppressive milieu is a goal of combination treatment approaches. Radiation has been used for over a century in the management of cancer with more than half of all cancer patients receiving radiotherapy. Here, we outline the rationale behind combining radiotherapy with ICB, a potential synergy through mutually beneficial remodelling of the TME. We discuss the pleiotropic effects radiation has on the TME including immunogenic cell death, activation of cytosolic DNA sensors, remodelling the stroma and vasculature, and paradoxical infiltration of both anti-tumour and suppressive immune cell populations. These events depend on the radiation dose and fractionation and optimising these parameters will be key to develop safe and effective combination regimens. Finally, we highlight ongoing efforts that combine radiation, immunotherapy and inhibitors of DNA damage response, which can help achieve a favourable equilibrium between the immunogenic and tolerogenic effects of radiation on the immune microenvironment.

'Flower of the body': menstrual experiences and needs of young adolescent women with cerebral palsy in Bangladesh, and their mothers providing menstrual support.

BACKGROUND: This study offers voice to young adolescent women with cerebral palsy (CP) in Bangladesh as they describe their menstrual experiences and needs, and their mothers providing menstrual support. METHOD: Semi-structured focus groups with adolescents with CP, and separately their mother. Data was analysed using a material discursive framework and drawing on feminist disability theory. Participants were recruited from the Bangladesh CP Register (BCPR); a population-based surveillance of children and adolescents with CP in rural Bangladesh. RESULTS: Participants were 45 women including 12 female adolescents with CP and 33 female caregivers. Participants reported a wide range of experiences and needs; menarche acted as a gateway to menstrual information although for some a discourse of silence prevailed due to exclusion from peer and familial networks. Menstruation was discursively constructed as a sign of 'female maturation' marked by an expectation of 'independence', required for acceptance into socially valued adult roles, and was positioned alongside increased vulnerability to sexual abuse. Young adolescent women with CP were expected to 'quietly endure' the material aspects of menstruation although unmanaged pain and distress were described. Mothers reported an imperative for meeting their adolescent's menstrual needs however this role was discursively positioned as 'painful', 'irritating' and 'shameful', in part due to an absence of affordable, functional menstrual resources. CONCLUSION: The findings of the present study provide motivation for disability services in Bangladesh to account for the menstrual needs of young adolescent women with CP within service delivery through strategies such as providing menstrual education and by embedding value in constructs such as 'interdependence'. Moreover, interventions focused on alleviating menstrual pain among young adolescent women with CP as well as those targeted to alleviate distress among mothers providing menstrual care are required. Finally, policy responses are required to ensure that 'inclusive development' considers the needs of menstruating women with disability.

A framework to measure the wildness of managed large vertebrate populations.

As landscapes continue to fall under human influence through habitat loss and fragmentation, fencing is increasingly being used to mitigate anthropogenic threats and enhance the commercial value of wildlife. Subsequent intensification of management potentially erodes wildness by disembodying populations from landscape-level processes, thereby disconnecting species from natural selection. Tools are needed to measure the degree to which populations of large vertebrate species in formally protected and privately owned wildlife areas are self-sustaining and free to adapt. We devised a framework to measure such wildness based on 6 attributes relating to the evolutionary and ecological dynamics of vertebrates (space, disease and parasite resistance, exposure to predation, exposure to limitations and fluctuations of food and water supply, and reproduction). For each attribute, we set empirical, species-specific thresholds between 5 wildness states based on quantifiable management interventions. We analysed data from 205 private wildlife properties with management objectives spanning ecotourism to consumptive utilization to test the framework on 6 herbivore species representing a range of conservation statuses and commercial values. Wildness scores among species differed significantly, and the proportion of populations identified as wild ranged from 12% to 84%, which indicates the tool detected site-scale differences both among populations of different species and populations of the same species under different management regimes. By quantifying wildness, this framework provides practitioners with standardized measurement units that link biodiversity with the sustainable use of wildlife. Applications include informing species management plans at local scales; standardizing the inclusion of managed populations in red-list assessments; and providing a platform for certification and regulation of wildlife-based economies. Applying this framework may help embed wildness as a normative value in policy and mitigate the shifting baseline of what it means to truly conserve a species.

Un Marco de Trabajo para Medir el Estado Salvaje de Poblaciones de Vertebrados Mayores bajo Manejo Resumen Conforme los paisajes siguen cayendo bajo la influencia del humano por causa de la pérdida del hábitat y la fragmentación, cada vez se usa más el encercado para mitigar las amenazas antropogénicas o incrementar el valor comercial de la fauna. La intensificación subsecuente del manejo tiene el potencial para erosionar el estado salvaje al desincorporar a las poblaciones de los procesos a nivel de paisaje, desconectando así a las especies del proceso de selección natural. Por lo tanto, se necesitan herramientas para medir el grado al cual las poblaciones de especies de vertebrados mayores dentro de áreas de fauna protegidas y privadas son autosostenibles y libres de adaptarse. Diseñamos un marco de trabajo para medir dicho estado salvaje con base en seis atributos relacionados con las dinámicas evolutivas y ecológicas de los vertebrados (espacio, resistencia a las enfermedades y a los parásitos, exposición a la depredación, exposición a las limitaciones y fluctuaciones en las reservas de agua y alimentos, y reproducción). Para cada atributo, establecimos umbrales empíricos y específicos por especie entre cinco estados salvajes basados en las intervenciones de manejo cuantificables. Usamos datos de 205 propiedades privadas de fauna con objetivos de manejo que abarcan desde el ecoturismo hasta el uso para consumo para probar el marco de trabajo en seis especies de herbívoros con una gama de estados de conservación y valores comerciales. Los puntajes de estado salvaje entre las especies difirieron significativamente y la proporción de poblaciones identificadas como salvajes osciló del 12% al 84%, lo que indica que la herramienta detectó diferencias a escala de sitio entre las poblaciones de diferentes especies y las poblaciones de la misma especie bajo diferentes regímenes de manejo. Si cuantificamos el estado salvaje, este marco de trabajo les proporciona a los practicantes las unidades de medida estandarizadas que vinculan a la biodiversidad con el uso sostenible de la fauna. Las aplicaciones de este marco de trabajo incluyen informar a los planes de manejo de las especies a escalas locales; estandarizar la inclusión de las poblaciones manejadas en las evaluaciones de listas rojas; y proporcionar una plataforma para la certificación y regulación de las economías basadas en la fauna. La aplicación de este marco de trabajo puede ayudar a insertar a la fauna como un valor normativo dentro de la política y a mitigar la línea base cambiante de lo que significa conservar verdaderamente a una especie.

Long-term outcomes of en-bloc renal transplantation from paediatric donors into adult recipients.

INTRODUCTION: Transplant units are exploring strategies to increase the availability of donor kidneys. The use of en-bloc kidney transplantation (EBKT) from paediatric donors represents one potential solution. We present our long-term experience with paediatric EBKT among adult recipients. METHODS: Twenty-three paediatric to adult EBKTs were performed by the Irish National Kidney Transplant Service between 1990 and 2016. The primary outcome variable was long-term en-bloc allograft survival rate. Secondary outcome variables were incidence of allograft thrombosis, incidence of delayed graft function, overall patient survival and serum creatinine at most recent follow-up. Outcomes were compared to single kidney transplant recipients from the same time period. RESULTS: Mean donor age was 1.8 ± 0.97 years (range: 7 months to 3 years). Recipient age was 46 ± 12 years. Mean follow-up was 133 ± 64 months (range: 36-264). Overall graft survival was 100%, 91% and 80% after 1, 5 and 10 years respectively, compared to 92%, 79% and 61% in single kidney transplant recipients (p = 0.04). There were 5 cases of allograft failure, 3 due to death from unrelated causes. Median time to graft failure was 108 months (range: 36-172). Mean serum creatinine was 72.6 ± 21.6 µmol/l after the follow-up period. There were no cases of graft thrombosis or delayed graft function. Overall survival was 96.4%, 88.0%, 76.23% and 50.5% at 1, 5, 10 and 20 years respectively. CONCLUSION: En-bloc paediatric kidney transplantation is associated with excellent long-term allograft and patient survival and is a feasible strategy for increasing the transplant donor pool in carefully selected recipients.

A Comparison of Perceived and Measured Paternal Weight and BMI, and Relationship to Weight and BMI of his Children.

INTRODUCTION: Nineteen percent of 9 years old Irish children are overweight; seven percent are obese. Our aims were: to examine whether differences exist between paternal self-reported and measured height, weight and BMI in a population representative sample; and to explore paternal perceptions of their own weight status. METHODS: Measures of height and weight for fathers and for their children from the National Longitudinal Study of Children Growing Up in Ireland were obtained using validated methods. RESULTS: Three quarters of fathers (6,263 of 8,568 study children) with a mean age of 42 years (SD 5.04) responded. The mean difference between self-reported and measured weight was -1.03kg (SD=4.52), indicating that weight was underestimated. Obese fathers were more likely to have an obese son (9.4% compared to 5.3% for the full cohort) and an obese daughter (12.4% compared to 7.7%). DISCUSSION: These data suggest that there is a strong relationship between fathers' weights and his childrens' weights. A leading factor in the development of childhood obesity is parental obesity. Targeting overweight and obesity in the child should occur simultaneously with tackling overweight and obesity in the parents; in this study, the fathers.

Patient reported functional outcomes following robotic-assisted (RARP), laparoscopic (LRP), and open radical prostatectomies (ORP).

BACKGROUND: Radical prostatectomy for prostate cancer is associated with significant complications, such as urinary incontinence and erectile dysfunction. Debate remains regarding the influence of surgical technique on these important functional outcomes. AIM: The aim of this study was to compare the early functional outcomes following robotic-assisted (RARP), laparoscopic (LRP), and open radical prostatectomy (ORP) in a rapid access cohort. METHODS: A retrospective review of a prospectively maintained database was performed between 2011 and 2014. Functional status was objectively assessed using the International Prostate Symptom Score (IPSS), International Index of Erectile Function (IIEF-5), and a self-reported continence score. RESULTS: Two hundred and ninety-two patients underwent RP (85 RARP, 100 LRP, 107 ORP). The mean age was 61.3 years with a mean initial PSA was 6.2 ng/ml. There was no difference noted in urinary function between ORP, LRP, and RARP at 3 months (p = 0.894), 6 months (p = 0.244), 9 months (p = 0.068) or 12 months (p = 0.154). All men noted a deterioration in erectile function; however, there was no difference at 3 months (p = 0.922), 6 months (p = 0.723), 9 months (p = 0.101) or 12 months (p = 0.395), CONCLUSION: Equivalent good early functional outcomes are being achieved in patients undergoing RP irrespective of surgical approach. Longer follow-up in a prospective randomized fashion is required to fully assess the most appropriate surgical technique.

Efficacy of vacuum erectile devices (VEDs) after radical prostatectomy: the initial Irish experience of a dedicated VED clinic.

Controversy exists regarding optimal penile rehabilitation program following radical prostatectomy (RP). Vacuum erectile devices (VEDs) have become an important component of penile rehabilitation protocols. The aim of this study was to assess the efficacy and patient satisfaction of a dedicated VED clinic. A voluntary telephone questionnaire was performed of all patients who attended a VED clinic to date in two university teaching hospitals. Patient demographics, histopathological characteristics and functional status (International Index of Erectile Function (IIEF) scores) were obtained from a retrospective review of a prospectively maintained database. Sixty-five men attended the dedicated VED clinic in the two university teaching hospitals. Forty-men (76.3%) men purchased a VED following the dedicated clinic. There was significant differences noted between the mean preoperative and the 3-month postoperative IIEF scores (22.08±3.16 vs 11.3±3.08, P=0.0001) and between the 3-month postoperative IIEF score and the post-VED use IIEF score (11.3±3.08 vs 16.74±2.62, P=0.0001). Despite VED use, there was a significant reduction in erectile function from presurgery status (22.08±3.16 vs 16.74±2.62, P=0.0001). All patients reported that the dedicated VED was helpful and would recommend it to other patients. Our study demonstrates that, despite a reduction in erectile function after RP, successful erections are attainable with a VED. There is potential and need for the development of a standard penile rehabilitation program and treatment of ED after RP internationally.

Inter-group violence among early Holocene hunter-gatherers of West Turkana, Kenya.

The nature of inter-group relations among prehistoric hunter-gatherers remains disputed, with arguments in favour and against the existence of warfare before the development of sedentary societies. Here we report on a case of inter-group violence towards a group of hunter-gatherers from Nataruk, west of Lake Turkana, which during the late Pleistocene/early Holocene period extended about 30 km beyond its present-day shore. Ten of the twelve articulated skeletons found at Nataruk show evidence of having died violently at the edge of a lagoon, into which some of the bodies fell. The remains from Nataruk are unique, preserved by the particular conditions of the lagoon with no evidence of deliberate burial. They offer a rare glimpse into the life and death of past foraging people, and evidence that warfare was part of the repertoire of inter-group relations among prehistoric hunter-gatherers.

Polygenic interactions with environmental adversity in the aetiology of major depressive disorder.

BACKGROUND: Major depressive disorder (MDD) is a common and disabling condition with well-established heritability and environmental risk factors. Gene-environment interaction studies in MDD have typically investigated candidate genes, though the disorder is known to be highly polygenic. This study aims to test for interaction between polygenic risk and stressful life events (SLEs) or childhood trauma (CT) in the aetiology of MDD. METHOD: The RADIANT UK sample consists of 1605 MDD cases and 1064 controls with SLE data, and a subset of 240 cases and 272 controls with CT data. Polygenic risk scores (PRS) were constructed using results from a mega-analysis on MDD by the Psychiatric Genomics Consortium. PRS and environmental factors were tested for association with case/control status and for interaction between them. RESULTS: PRS significantly predicted depression, explaining 1.1% of variance in phenotype (p = 1.9 × 10(-6)). SLEs and CT were also associated with MDD status (p = 2.19 × 10(-4) and p = 5.12 × 10(-20), respectively). No interactions were found between PRS and SLEs. Significant PRSxCT interactions were found (p = 0.002), but showed an inverse association with MDD status, as cases who experienced more severe CT tended to have a lower PRS than other cases or controls. This relationship between PRS and CT was not observed in independent replication samples. CONCLUSIONS: CT is a strong risk factor for MDD but may have greater effect in individuals with lower genetic liability for the disorder. Including environmental risk along with genetics is important in studying the aetiology of MDD and PRS provide a useful approach to investigating gene-environment interactions in complex traits.

Single centre experience of hypothermic machine perfusion of kidneys from extended criteria deceased heart-beating donors: a comparative study.

INTRODUCTION: Kidneys from extended criteria donors are associated with higher rates of delayed graft function (DGF). Hypothermic machine perfusion (MP) for storage is associated with more favourable outcomes. METHODS: A retrospective analysis was performed in 93 patients where the kidney was stored using hypothermic MP (LifePort(®)) and compared to an age-matched control group where the kidney was stored in cold static storage (CSS) using University of Wisconsin solution. RESULTS: Median age was similar in both groups (59.2 years in MP vs 59.9 years in CSS, p = 0.5598). Mean cold storage time was 15.6 h in MP vs 17.9 h in CSS. Post transplant mean serum creatinine was as follows; MP group-144.7 µmol/L at 1 month; 138.3 µmol/L at 3 months and 129.5 µmol/L at 12 months. In the CSS group-163 µmol/L at 1 month; 154.9 µmol/L at 3 months and 140.2 µmol/L at 12 months. There was a statistically significant difference at 1 month (p = 0.0096) and 3 months (p = 0.0236). DGF was defined as the need for haemodialysis within 7 days post transplant. In the MP group, DGF occurred in 17.2 % patients with mean of 6 days (range 1-18). In the CSS group, 25.8 % patients with mean of 8.1 days (range 3-25). One-year graft survival rate was better in the MP group (97.85 vs 96.77 %). CONCLUSION: Our experience to date recommends the use of hypothermic MP for storage of kidneys from extended criteria deceased heart-beating donors.

Heritability estimates of the Big Five personality traits based on common genetic variants.

According to twin studies, the Big Five personality traits have substantial heritable components explaining 40-60% of the variance, but identification of associated genetic variants has remained elusive. Consequently, knowledge regarding the molecular genetic architecture of personality and to what extent it is shared across the different personality traits is limited. Using genomic-relatedness-matrix residual maximum likelihood analysis (GREML), we here estimated the heritability of the Big Five personality factors (extraversion, agreeableness, conscientiousness, neuroticism and openness for experience) in a sample of 5011 European adults from 527,469 single-nucleotide polymorphisms across the genome. We tested for the heritability of each personality trait, as well as for the genetic overlap between the personality factors. We found significant and substantial heritability estimates for neuroticism (15%, s.e. = 0.08, P = 0.04) and openness (21%, s.e. = 0.08, P < 0.01), but not for extraversion, agreeableness and conscientiousness. The bivariate analyses showed that the variance explained by common variants entirely overlapped between neuroticism and openness (rG = 1.00, P < 0.001), despite low phenotypic correlation (r = - 0.09, P < 0.001), suggesting that the remaining unique heritability may be determined by rare or structural variants. As far as we are aware of, this is the first study estimating the shared and unique heritability of all Big Five personality traits using the GREML approach. Findings should be considered exploratory and suggest that detectable heritability estimates based on common variants is shared between neuroticism and openness to experiences.

Familiality and SNP heritability of age at onset and episodicity in major depressive disorder.

BACKGROUND: Strategies to dissect phenotypic and genetic heterogeneity of major depressive disorder (MDD) have mainly relied on subphenotypes, such as age at onset (AAO) and recurrence/episodicity. Yet, evidence on whether these subphenotypes are familial or heritable is scarce. The aims of this study are to investigate the familiality of AAO and episode frequency in MDD and to assess the proportion of their variance explained by common single nucleotide polymorphisms (SNP heritability). METHOD: For investigating familiality, we used 691 families with 2-5 full siblings with recurrent MDD from the DeNt study. We fitted (square root) AAO and episode count in a linear and a negative binomial mixed model, respectively, with family as random effect and adjusting for sex, age and center. The strength of familiality was assessed with intraclass correlation coefficients (ICC). For estimating SNP heritabilities, we used 3468 unrelated MDD cases from the RADIANT and GSK Munich studies. After similarly adjusting for covariates, derived residuals were used with the GREML method in GCTA (genome-wide complex trait analysis) software. RESULTS: Significant familial clustering was found for both AAO (ICC = 0.28) and episodicity (ICC = 0.07). We calculated from respective ICC estimates the maximal additive heritability of AAO (0.56) and episodicity (0.15). SNP heritability of AAO was 0.17 (p = 0.04); analysis was underpowered for calculating SNP heritability of episodicity. CONCLUSIONS: AAO and episodicity aggregate in families to a moderate and small degree, respectively. AAO is under stronger additive genetic control than episodicity. Larger samples are needed to calculate the SNP heritability of episodicity. The described statistical framework could be useful in future analyses.

Active surveillance for low-risk prostate cancer: diversity of practice across Europe.

BACKGROUND: Active surveillance (AS) is a recognised treatment option for low-risk prostate cancer (PCa). AIMS: To review AS criteria in terms of patient selection, follow-up and indications for intervention. METHODS: A total of 2,959 potential participants were identified and invited via email to complete an online survey. Only urologists practising in an EU country were eligible to participate. Statistical analyses were carried out using SPSS version 18.0. The χ (2) test was used to compare responses between those who do and do not follow an AS protocol. RESULTS: Response rate was 8% (n = 226). Ninety-seven per cent urologists offer AS; 25% (n = 53/215) within a clinical trial and a further 28% (n = 60/215) using an official AS protocol. Gleason score ≤ 3 + 3 = 6 (87 %, n = 173/200) and prostate-specific antigen (PSA) ≤ 10 ng/ml (86%, n = 170/198) are the commonest selection criteria. There was a statistically significant association between having an AS protocol and using PSA as an eligibility criterion (p = 0.03). For urologists not following a protocol, 11% do not consider PSA as an eligibility criterion and 81% consider PSA ≤ 10 ng/ml to decide on AS, compared to 2 and 90%, respectively, who adhere to a protocol. Twenty-four per cent of urologists without a protocol do not re-biopsy in comparison to 11% with a protocol (p = 0.026). Gleason score progression trigger the most intervention (n = 168/192, 87%). CONCLUSIONS: Urologists not adhering to an AS protocol or participating in a clinical trial appear to apply less rigorous criteria for both eligibility and monitoring in AS.

Tongue-tie and frenotomy in infants with breastfeeding difficulties: achieving a balance.

AIMS: Currently there is debate on how best to manage young infants with tongue-tie who have breastfeeding problems. One of the challenges is the subjectivity of the outcome variables used to assess efficacy of tongue-tie division. This structured review documents how the argument has evolved. It proposes how best to assess, inform and manage mothers and their babies who present with tongue-tie related breastfeeding problems. METHODS: Databases were searched for relevant papers including Pubmed, Medline, and the Cochrane Library. Professionals in the field were personally contacted regarding the provision of additional data. Inclusion criteria were: infants less than 3 months old with tongue-tie and/or feeding problems. The exclusion criteria were infants with oral anomalies and neuromuscular disorders. RESULTS: There is wide variation in prevalence rates reported in different series, from 0.02 to 10.7%. The most comprehensive clinical assessment is the Hazelbaker Assessment Tool for lingual frenulum function. The most recently published systematic review of the effect of tongue-tie release on breastfeeding concludes that there were a limited number of studies with quality evidence. There have been 316 infants enrolled in frenotomy RCTs across five studies. No major complications from surgical division were reported. The complications of frenotomy may be minimised with a check list before embarking on the procedure. CONCLUSIONS: Good assessment and selection are important because 50% of breastfeeding babies with ankyloglossia will not encounter any problems. We recommend 2 to 3 weeks as reasonable timing for intervention. Frenotomy appears to improve breastfeeding in infants with tongue-tie, but the placebo effect is difficult to quantify. Complications are rare, but it is important that it is carried out by a trained professional.