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Supplementary Figures 1-3 from Tissue-Specific Pathways for Estrogen Regulation of Ovarian Cancer Growth and Metastasis

Supplementary Tables 1-4 from Tissue-Specific Pathways for Estrogen Regulation of Ovarian Cancer Growth and Metastasis

Ge1–xSnx nanowires incorporating a large amount of Sn would be useful for mobility enhancement in nanoelectronic devices, a definitive transition to a direct bandgap for application in optoelectronic devices and to increase the efficiency of the GeSn-based photonic devices. Here we report the catalytic bottom-up fabrication of Ge1–xSnx nanowires with very high Sn incorporation (x > 0.3). These nanowires are grown in supercritical toluene under high pressure (21 MPa). The introduction of high pressure in the vapor–liquid–solid (VLS) like growth regime resulted in a substantial increase of Sn incorporation in the nanowires, with a Sn content ranging between 10 and 35 atom %. The incorporation of Sn in the nanowires was found to be inversely related to nanowire diameter; a high Sn content of 35 atom % was achieved in very thin Ge1–xSnx nanowires with diameters close to 20 nm. Sn was found to be homogeneously distributed throughout the body of the nanowires, without apparent clustering or segregation. The large inclusion of Sn in the nanowires could be attributed to the nanowire growth kinetics and small nanowire diameters, resulting in increased solubility of Sn in Ge at the metastable liquid–solid interface under high pressure. Electrical investigation of the Ge1–xSnx (x = 0.10) nanowires synthesized by the supercritical fluid approach revealed their potential in nanoelectronics and sensor-based applications.

The Ptolemaic era (305–30 BCE) is an important period of Ancient Egyptian history known for its material and scientific advances, but also intermittent political and social unrest in the form of (sometimes widespread) revolts against the Ptolemaic elites. While the role of environmental pressures has long been overlooked in this period of Egyptian history, ice-core-based volcanic histories have identified the period as experiencing multiple notable eruptions, and a repeated temporal association between explosive volcanism and revolt has recently been noted. Here we analyze the global and regional (Nile River basin) hydroclimatic response to a unique historical sequence of four large and closely timed volcanic eruptions (first a tropical one, followed by three extratropical northern hemispheric events) between 168 and 158 BCE, a particularly troubled period in Ptolemaic history for which we now provide a more detailed hydroclimatic context. The NASA (National Aeronautics and Space Administration) GISS (Goddard Institute for Space Studies) ModelE2.1 Earth system model simulates a strong radiative response with a radiative forcing (top of atmosphere) of −7.5 W m−2 (following the first eruption) and −2.5 W m−2 (after each of the three remaining eruptions) at a global scale. Associated with this, we observe a global surface cooling of the order of 1.5 ∘C following the first (tropical) eruption, with the following three extratropical eruptions extending the cooling period for more than 15 years. Consequently, this series of eruptions is observed to constrain the northward migration of the inter-tropical convergence zone (ITCZ) during the Northern Hemisphere summer monsoon season, and major monsoon zones (African, South Asian, and East Asian) were seen to experience a suppression of rainfall of >1 mm d−1 during the monsoon (JJAS) season averaged for 2 years after each eruption. A substantial suppression of the Indian and North African summer monsoon (over the Nile River headwater region) was seen to strongly affect the modeled river flow in the catchment and discharge at river mouth. River mass flow over the basin was observed to decrease by 29 % and 38 % relative to an unperturbed (non-volcanic) annual mean flow in the first and second year, respectively, after the first (i.e., tropical) eruption. A moderate decrease ranging between 5 % and 18 % was observed after the third and fourth (extratropical) eruptions. These results indicate, in sum, that the first eruption likely produced a strong hydroclimate response, with the following extratropical eruptions prolonging this. These results also support the recently hypothesized association between ice-core-based signals of explosive volcanism and hydroclimatic variability during the Ptolemaic era, including the suppression of the agriculturally critical Nile summer flooding.

Acquired tracheomegaly is a rare condition associated with pulmonary fibrosis, connective tissue disease and the use of cuffed tracheal tubes. We describe the urgent tracheal re‐intubation and subsequent tracheal repair of a previously well 58‐year‐old man who developed tracheostomy‐related tracheomegaly during prolonged mechanical ventilation for coronavirus disease 2019 pneumonitis. Urgent tracheal re‐intubation was required due to a persistent cuff leak, pneumomediastinum and malposition of the tracheostomy tube. We describe the additional challenges and risks associated with airway management in patients with tracheomegaly, and discuss how even in urgent cases these can be mitigated through planning and teamwork. We present a stepwise approach to tracheal re‐intubation past a large tracheal dilatation, including the use of an Aintree catheter inserted via the existing tracheal stoma for oxygenation or tracheal re‐intubation if required. Computed tomography imaging was valuable in characterising the defect and developing a safe airway management strategy before starting the procedure. This report emphasises the role of planning, teamwork and the development of an appropriate airway strategy in the safe management of complex cases.

Background Laparoscopic cholecystectomy (LC) is the gold standard for the treatment of cholelithiasis in most countries of the world. The objective of this study was to evaluate the outcomes of LC in the surgery department of Cure International Hospital, Kabul, Afghanistan. Methods A retrospective study was conducted on 1430 LC cases performed by the general surgery department of Cure International Hospital. Data was collected from patient files and the operation theatre registry for whom LC was performed during January 2008 through December, 2019. Results Mean age was 45.77 ± 13.45 years (14–90 years), with male/female ratio of 1:4.7. One third (33%) had comorbidities. Most of patients (~ 97%) were classified as ASA grade I and II. Of all patients, 26.8% of males and 13.2% of females had gallbladder inflammation (OR = 2.203, 95% CI 1.56–2.61, P = 0.000). Overall mean duration of anesthesia was 75 ± 25.6 min. The conversion rate to OC was 4.6% (N = 66), most commonly dense adhesions at Callot’s triangle (3.8%). The intraoperative complication rate was 17.5% (N = 249), where bile/stone spillage was the most common indication (N = 235, 16.4%). Immediate postoperative complication rate was 2.4% (N = 35). Average length of stay (ALOS) after LC was 2.23 ± 1.43 days (1–19 days). Conclusion This study shows that elective LC can be performed safely in Afghanistan with comparable outcomes in terms of complications, conversion rates, and ALOS to other countries of the region and the world. Proper case selection and careful preoperative evaluation and management can decrease further conversion, intra- and postoperative complications.

Networks of metallic nanowires have the potential to meet the needs of next-generation device technologies that require flexible transparent conductors. At present, there does not exist a first principles model capable of predicting the electro-optical performance of a nanowire network. Here we combine an electrical model derived from fundamental material properties and electrical equations with an optical model based on Mie theory scattering of light by small particles. This approach enables the generation of analogues for any nanowire network and then accurately predicts, without the use of fitting factors, the optical transmittance and sheet resistance of the transparent electrode. Predictions are validated using experimental data from the literature of networks comprised of a wide range of aspect ratios (nanowire length/diameter). The separation of the contributions of the material resistance and the junction resistance allows the effectiveness of post-deposition processing methods to be evaluated and provides a benchmark for the minimum attainable sheet resistance. The predictive power of this model enables a material-by-design approach, whereby suitable systems can be prescribed for targeted technology applications.

Considerable attention has been drawn to the lead halide perovskites (LHPs) because of their outstanding optoelectronic characteristics. LHP nanosheets (NSs) grown from single crystalline lead halide possess advantages in device applications as they provide the possibility for control over morphology, composition, and crystallinity. Here, free-standing lead bromide (PbBr2) single-crystalline NSs with sizes up to one centimeter are synthesized from solution. These NSs can be converted to LHP while maintaining the NS morphology. We demonstrate that these perovskite NSs can be processed directly for fabrication of photodetector and laser arrays on a large scale. This strategy will allow high-yield synthesis of large-size perovskite NSs for functional devices in an integrated photonics platform.

Introduction and Objectives: Renal cell carcinoma (RCC) accounts for 2–3% of all cancers. With increasing use of Computer Tomography, a large proportion are detected earlier and amenable to focal therapies such as Radiofrequency Ablation (RFA). Our institution is unable to offer image‐guided percutaneous ablation (PA) through the public service due to lack of Interventional Radiology (IR) resources. Currently, patients with a small renal mass (SRM) are either actively observed, undergo radical nephrectomy (RN), partial nephrectomy (PN) or referred to another tertiary institution for focal therapy. Recent studies have demonstrated no difference in long‐term efficacy between RN, PN and PA treatment of SRMs in selected patients; but with significantly higher rates of morbidity in the surgical treatment groups. Our Urology Multidisciplinary Team (MDT) is supported by an interventional radiologist with Uroradiology specialisation who provides PA for our patients through a private facility and we assessed the cost‐effectiveness of our institution outsourcing PA . The aim of the study was to compare the costs associated with performing nephrectomies (RN, PN) in a public hospital with the costs of performing minimally invasive PA in a private hospital; and to assess the financial impact on the public system of the different treatment options for SRMs. Methods: The cost of performing PA at a large tertiary private hospital for patients with a SRM (

Climate change over the past thousands of years is undeniable, but debate has arisen about its impact on past human societies. This book explores the link between climate and society in ancient worlds, focusing on the ancient economies of western Eurasia and northern Africa from the fourth millennium BCE up to the end of the first millennium CE. This book contributes to the multi-disciplinary debate between scholars working on climate and society from various backgrounds. The chronological boundaries of the book are set by the emergence of complex societies in the Neolithic on the one end and the rise of early-modern states in global political and economic exchange on the other. In order to stimulate comparison across the boundaries of modern periodization, this book ends with demography and climate change in early-modern and modern Italy, a society whose empirical data allows the kind of statistical analysis that is impossible for ancient societies. The book highlights the role of human agency, and the complex interactions between the natural environment and the socio-cultural, political, demographic, and economic infrastructure of any given society. It is intended for a wide audience of scholars and students in ancient economic history, specifically Rome and Late Antiquity.

Graphical abstract, Engineering of self-disinfecting surfaces to constrain the spread of SARS-CoV-2 is a challenging task for the scientific community, because the human coronavirus spreads through respiratory droplets. Titania (TiO2) nanocomposite antimicrobial coatings is one of the ideal remedies to disinfect pathogens (virus, bacteria, fungi) from common surfaces under light illumination. The photocatalytic disinfection efficiency of recent TiO2 nanocomposite antimicrobial coatings for surfaces, dental and orthopaedic implants are emphasized in this review. Mostly, inorganic metals (e.g. copper (Cu), silver (Ag), manganese (Mn), etc), non-metals (e.g. fluorine (F), calcium (Ca), phosphorus (P)) and two-dimensional materials (e.g. MXenes, MOF, graphdiyne) were incorporated with TiO2 to regulate the charge transfer mechanism, surface porosity, crystallinity, and the microbial disinfection efficiency. The antimicrobial activity of TiO2 coatings was evaluated against the most crucial pathogenic microbes such as Escherichia coli, methicillin-resistant Staphylococcus aureus, Pseudomonas aeruginosa, Bacillus subtilis, Legionella pneumophila, Staphylococcus aureus, Streptococcus mutans, T2 bacteriophage, H1N1, HCoV-NL63, vesicular stomatitis virus, bovine coronavirus. Silane functionalizing agents and polymers were used to coat the titanium (Ti) metal implants to introduce superhydrophobic features to avoid the microbial adhesion. TiO2 nanocomposite coatings in dental and orthopaedic metal implants disclosed an exceptional bio-corrosion resistance, durability, biocompatibility, bone-formation capability, and long-term antimicrobial efficiency. Moreover, the commercial trend, techno-economics, challenges, and prospects of antimicrobial nanocomposite coatings are also discussed briefly.

Rationale Food allergy is documented to result in considerable morbidity, negative impact on quality of life, and substantial medical care costs. Although anecdotal data suggest widely varying practices in the diagnosis and management of food allergies, the diversity and relative frequency of these practices have not been documented. Methods A questionnaire was developed evaluating allergists’ management approaches of individuals with peanut allergy (PA) in Germany (DE), France (FR), and the United Kingdom (UK). Results Here, we report the survey results from a total of 109 allergists from DE, FR and the UK. They reported to confirm PA at initial diagnosis using skin prick test (≥60%), while allergists from DE and FR reported using allergen-specific IgE testing more (>86%) compared to the UK (75%). Half of the responders reported assessing the patient’s quality of life. 63% allergists reported retesting for PA resolution at a later date, with 45% allergists indicated to recommend ingestion of a normal serving of peanut regularly upon resolution. Lack of effective PA treatment was reported to be a ‘very significant’ barrier for optimal PA treatment, with allergists being less than ‘moderately familiar’ with data from clinical trials testing new treatments options for PA. Lastly, allergists stated that the severity of patient’s PA ranked as the most important factor in their decision to recommend oral immunotherapy for PA treatment. Conclusions This survey provides essential insights into the practice of allergists and highlights some areas that would inform strategies for education and improving PA healthcare.

Funding: National Science Foundation grants 1925417, 1023672, and 0909541 to J.R.M., and 1824770 to J.G.M. and F.M.L. funded this research, as well as support to A.I.W. and J.R.M. from the John Fell Oxford University Press (OUP) Research Fund and All Souls College, Oxford. Clare Hall, Cambridge provided additional support to J.R.M. through the Sir Nicholas Shackleton fellowship. F.M.L. also acknowledges support from an Irish Research Council Laureate Award (CLICAB project, IRCLA/2017/303). Swiss National Science Foundation grant 18001 funded C.C.R. and W.M.K. European Research Council grant 820047 under the European Union’s Horizon 2020 research and innovation programme supported M.S. A.B. was supported by Marie Curie Career Integration Grant CIG14-631752. The assassination of Julius Caesar in 44 BCE triggered a power struggle that ultimately ended the Roman Republic and, eventually, the Ptolemaic Kingdom, leading to the rise of the Roman Empire. Climate proxies and written documents indicate that this struggle occurred during a period of unusually inclement weather, famine, and disease in the Mediterranean region; historians have previously speculated that a large volcanic eruption of unknown origin was the most likely cause. Here we show using well-dated volcanic fallout records in six Arctic ice cores that one of the largest volcanic eruptions of the past 2,500 y occurred in early 43 BCE, with distinct geochemistry of tephra deposited during the event identifying the Okmok volcano in Alaska as the source. Climate proxy records show that 43 and 42 BCE were among the coldest years of recent millennia in the Northern Hemisphere at the start of one of the coldest decades. Earth system modeling suggests that radiative forcing from this massive, high-latitude eruption led to pronounced changes in hydroclimate, including seasonal temperatures in specific Mediterranean regions as much as 7 °C below normal during the 2 y period following the eruption and unusually wet conditions. While it is difficult to establish direct causal linkages to thinly documented historical events, the wet and very cold conditions from this massive eruption on the opposite side of Earth probably resulted in crop failures, famine, and disease, exacerbating social unrest and contributing to political realignments throughout the Mediterranean region at this critical juncture of Western civilization. Postprint

INTRODUCTION AND OBJECTIVE:Renal colic is a common urological problem with a lifetime incidence of approximately 8-19% in males and 3-5% in females. The MIMIC Study was a 4171 patient cohort study ...

Brain-inspired, neuromorphic computing aims to address the growing computational complexity and power consumption in modern von-Neumann architectures. Progress in this area has been hindered due to the lack of hardware elements that can mimic neuronal/synaptic behavior which form the fundamental building blocks for spiking neural networks (SNNs). In this work, we leverage the short/long term memory effects due to the electron trapping events in an atomically thin channel transistor that mimic the exchange of neurotransmitters and emulate a synaptic response. Re-doped (n-type) and Nb-doped (p-type) molybdenum di-sulfide (MoS2) field-effect transistors are examined using pulsed-gate measurements, which identify the time scales of electron trapping/de-trapping. The devices demonstrate promising trends for short/long term plasticity in the order of ms/minutes, respectively. Interestingly, pulse paired facilitation (PPF), which quantifies the short-term plasticity, reveal time constants (τ1 = 27.4 ms, τ2 = 725 ms) that closely match those from a biological synapse. Potentiation and depression measurements describe the ability of the synaptic device to traverse several analog states, where at least 50 conductance values are accessed using consecutive pulses of equal height and width. Finally, we demonstrate devices, which can emulate a well-known learning rule, spike time-dependent plasticity (STDP) which codifies the temporal sequence of pre- and post-synaptic neuronal firing into corresponding synaptic weights. These synaptic devices present significant advantages over iontronic counterparts and are envisioned to create new directions in the development of hardware for neuromorphic computing.

Background: Occupational health laws must recognise the constitutional requirement of substantive equality, and its role in ‘the progressive realisation’ of the rights provided by Section 27. Objectives: Our main aim is to review current South African occupational health law (vis-a-vis workers’ constitutional rights) in relation to hearing loss. We focus on gaps in the law regarding occupational hearing loss in South Africa. Method: Our review of legal texts relies on experience as a methodological device augmented by the use of a critical science. Guided by literature or evidence synthesis methodologies, South African primary and secondary laws were reviewed along with unpublished (non-peer-reviewed) grey literature. An established six-step framework guided our thematic analysis. A semantic approach aided the critical interpretation of data using the Bill of Rights as a core analytical framework. Results: Four themes are discussed: (1) separate and unequal regulatory frameworks; (2) monologic foregrounding of noise; (3) minimisation of vestibular disorders; and (4) dilution of ototoxic agents. The highly divided legal framework of occupational health and safety in South Africa perpetuates a monologic ‘excessive noise-hearing loss’ paradigm that has implications for the rights of all workers to equal protections and benefits. There is a need to harmonise occupational health and safety law, and expand the scope of hearing-protection legislation to include the full range of established ototoxic hazards. Conclusion: Occupational audiology is dominated by efforts to address noise-induced hearing loss. A ‘noise’ despite the reality of workers’ exposures to a range of ototoxic stressors that act synergistically on the ear, resulting in audio-vestibular disorders.

Here the controlled growth of SnSe nanowires by a liquid injection chemical vapor deposition (CVD) method employing a distorted octahedral [SnCl4{n BuSe(CH2)3Sen Bu}] single‐source diselenoether precursor is reported. CVD with this single‐source precursor allows morphological and compositional control of the SnSex nanostructures formed, including the transformation of SnSe2 nanoflakes into SnSe nanowires and again to SnSe nanoflakes with increasing growth temperature. Significantly, highly crystalline SnSe nanowires with an orthorhombic Pnma 62 crystal structure can be controllably synthesized in two growth directions, either or . The ability to tune the growth direction of SnSe will have important implications for devices constructed using these nanocrystals. The SnSe nanowires with a growth direction display a reversible polarity‐dependent memory switching ability, not previously reported for nanoscale SnSe. A resistive switching on/off ratio of 103 without the use of a current compliance limit is seen, illustrating the potential use of SnSe nanowires for low‐power nonvolatile memory applications., Raw data from publication Adv. Mater. Inter. 2020, 2000474(1-10).

Introduction Strengthening The Reporting Of Cohort Studies in Surgery (STROCSS) guidelines were developed in 2017 in order to improve the reporting quality of observational studies in surgery and updated in 2019. In order to maintain relevance and continue upholding good reporting quality among observational studies in surgery, we aimed to update STROCSS 2019 guidelines. Methods A STROCSS 2021 steering group was formed to come up with proposals to update STROCSS 2019 guidelines. An expert panel of researchers assessed these proposals and judged whether they should become part of STROCSS 2021 guidelines or not, through a Delphi consensus exercise. Results 42 people (89%) completed the DELPHI survey and hence participated in the development of STROCSS 2021 guidelines. All items received a score between 7 and 9 by greater than 70% of the participants, indicating a high level of agreement among the DELPHI group members with the proposed changes to all the items. Conclusion We present updated STROCSS 2021 guidelines to ensure ongoing good reporting quality among observational studies in surgery., Highlights • In order to maintain relevance and continue upholding good reporting quality among observational studies in surgery, STROCSS 2019 guidelines were updated through a DELPHI consensus exercise. • 42 people participated in the development of STROCSS 2021 guidelines and there was a high level of agreement among the DELPHI group members with the proposed changes to all the items. • Updated STROCSS 2021 guideline is presented.

BACKGROUND Surgical operation notes are crucial for medical record keeping and information flow in continued patient care. In addition to inherent medical implications, the quality of operative notes also has important economic and medico-legal ramifications. Further, well-documented records can also be useful for audit purposes and propagation of research, facilitating the improvement of delivery of care to patients. We aimed to assess the quality of surgical operation notes written by junior doctors and trainees against a set standard, to ascertain whether these standards were met. METHOD We undertook an audit of Urology and General Surgery operation notes handwritten by junior doctors and surgical trainees in a tertiary teaching hospital over a month period both in 2014 and 2015. Individual operative notes were assessed for quality based on parameters described by the Royal College of Surgeons of England guidelines. RESULTS Based on the Royal College of Surgeons of England guidelines, a significant proportion of analysed surgical operative notes were incomplete, with information pertaining to the time of surgery, name of anaesthetist and deep vein thrombosis prophylaxis in particular being recorded less than 50% of the time (22.42, 36.36 and 43.03%, respectively).Overall, 80% compliance was achieved in 14/20 standards and 100% compliance was attained in only one standard. CONCLUSIONS The quality of surgical operation notes written by junior doctors and trainees demonstrated significant deficiencies when compared against a set standard. There is a clear need to educate junior medical staff and to provide systems and ongoing education to improve quality. This would involve leadership from senior staff, ongoing audit and the development of systems that are part of the normal workflow to improve quality and compliance.

Background Aeromonas hydrophila (AH) is a rare gram-negative anaerobic bacterium that is usually found in freshwater and contaminated soils. AH may behave in a pathogenic manner and a majority of the literature reports clinical manifestations of significant infection – typically in the immunocompromised. However, recent genomic typing of the bacterium has led to the discovery of a less virulent but antibiotic resistant strain which may be responsible for colonisation rather than infection. Case report We present an example of successful graft uptake in the presence of heavy graft site growth of Aeromonas hydrophila . Discussion Contemporary literature is yet to make the distinction between colonisation and infection of this bacterium, with clinicians relying solely on the presence of infective stigmata and serum analysis. However, this is a critically important distinction when ascertaining the likelihood of success of wound healing.

Background: Contemporary recommendations regarding the duration of follow-up after radical prostatectomy (RP) are highly heterogeneous. Protocol-based follow-up schemes have been implemented to facilitate the expeditious identification of patients with recurrence. The aim of this study is to assess the reliability and comfort of general practitioners (GPs) in follow-up of RP. Methods: Following institutional ethical approval, we performed a retrospective review in patients undergoing follow-up after RP between January 2004 and December 2010. Patient factors, disease variables, and follow-up prostate specific antigen (PSA) compliance was collected. “Noncompliant” follow-up care was defined as: patients that had not received a PSA for a 14 month period within 5 years of prostatectomy. Patient and disease-based risk factors for noncompliant follow-up were assessed. GPs were also surveyed in their follow-up practice of RP patients, to assess their familiarity in caring for these patients. Results: In total, 65 cases were identified that met the inclusion criteria. At 60 months of follow-up, 66% (43/65) of patients had a compliant follow-up regime. For patients with noncompliant follow-up at 60 months, median time of compliance did not differ significantly when assessing preoperative PSA, Gleason sum, extraprostatic extension, or surgical margin status. Of the GPs surveyed, 68% of GPs felt comfortable in follow-up of RP patients. Some 62% of GPs would expect the PSA to be < 0.1 and 25% of GPs would measure the PSA annually. Conclusion: Our study identified that follow-up by GPs after RP is insufficient. Accordingly, there is a requirement for formal educational programs if primary care is to take a greater role in follow-up of these patients.

Purpose Localised prostate cancer diagnosis and management is increasingly complex due to its heterogeneous progression and prognostic subgroups. Pitfalls in current screening and diagnosis have prompted the search for accurate and invasive molecular and genetic biomarkers for prostate cancer. Such tools may be able to distinguish clinically significant cancers from less aggressive variants to assist with prostate cancer risk stratification and guide decisions and healthcare algorithms. We aimed to provide a comprehensive review of the current prostate cancer biomarkers available and in development. Methods MEDLINE and EMBASE databases searches were conducted to identify articles pertaining to the use of novel biomarkers for prostate cancer. Results A growing number of novel biomarkers are currently under investigation. Such markers include urinary biomarkers, serology-based markers or pathological tissue assessments of molecular and genetic markers. While limited clinical data is present for analysis, early results appear promising. Specifically, a combination of serum and urinary biomarkers (Serum PSA + Urinary PCA3 + Urinary TMPRSS2-ERG fusion) appears to provide superior sensitivity and specificity profiles compared to traditional diagnostic approaches (AUC 0.88). Conclusion The accurate diagnosis and risk stratification of prostate cancer is critical to ensure appropriate intervention. The development of non-invasive biomarkers can add to the information provided by current screening practices and allows for individualised risk stratification of patients. The use of these biomarkers appears to increase the sensitivity and specificity of diagnosis of prostate cancer. Further studies are necessary to define the appropriate use and time points of each biomarker and their effect on the management algorithm of prostate cancer.

Item does not contain fulltext Trainee-led collaboratives offer exciting new perspectives and approaches to urological research. They provide a central network of expertise in methodology, mentoring, and knowledge of research processes that allows the conduct of large multicentre studies that can recruit quickly. This provides the consultant workforce of tomorrow with the skills required to deliver practice-changing clinical studies in urology.

Mutual exclusivity analysis of genomic mutations has proven useful for detecting driver alterations in cancer patient cohorts. Here we demonstrate, for the first time, that this pattern is also present among de novo mutations in autism spectrum disorder. We analyzed three large whole genome sequencing studies and identified mutual exclusivity patterns within the most confident set of autism-related genes, as well as in the circadian clock and PI3K/AKT signaling pathways.

Acute Myeloid Leukemia (AML) develops due to the acquisition of mutations from multiple functional classes. Here, we demonstrate that activating mutations in the granulocyte colony stimulating factor receptor (CSF3R), cooperate with loss of function mutations in the transcription factor CEBPA to promote acute leukemia development. The interaction between these distinct classes of mutations occurs at the level of myeloid lineage enhancers where mutant CEBPA prevents activation of a subset of differentiation associated enhancers. To confirm this enhancer-dependent mechanism, we demonstrate that CEBPA mutations must occur as the initial event in AML initiation. This improved mechanistic understanding will facilitate therapeutic development targeting the intersection of oncogene cooperativity., Acute Myeloid Leukemia (AML) develops following multiple mutations of differing impact. Here, the authors show that activating mutations of CSF3R co-operate with loss-of-function mutations of CEBPA to promote AML development through an enhancer-dependent mechanism.

Motivated by numerous technological applications, there is current interest in the study of the conductive properties of networks made of randomly dispersed nanowires. The sheet resistance of such networks is normally calculated by numerically evaluating the conductance of a system of resistors but due to disorder and with so many variables to account for, calculations of this type are computationally demanding and may lack mathematical transparency. Here we establish the equivalence between the sheet resistance of disordered networks and that of a regular ordered network. Rather than through a fitting scheme, we provide a recipe to find the effective medium network that captures how the resistance of a nanowire network depends on several different parameters such as wire density, electrode size and electrode separation. Furthermore, the effective medium approach provides a simple way to distinguish the sheet resistance contribution of the junctions from that of the nanowires themselves. The contrast between these two contributions determines the potential to optimize the network performance for a particular application.