Histographic analysis of oedema and fat in inflamed bone marrow based on quantitative MRI.

Objective: To demonstrate proof-of-concept for a quantitative MRI method using histographic analysis to assess bone marrow oedema and fat metaplasia in the sacroiliac joints.

Materials And Methods: Fifty-three adolescents aged 12-23 with known or suspected sacroiliitis were prospectively recruited and underwent quantitative MRI (qMRI) scans, consisting of chemical shift-encoded (at 3 T) and diffusion-weighted imaging (at 1.5 T), plus conventional MRI (at 1.

Prognostic significance of troponin level in 3121 patients presenting with atrial fibrillation (The NIHR Health Informatics Collaborative TROP-AF study).

Background Patients presenting with atrial fibrillation (AF) often undergo a blood test to measure troponin, but interpretation of the result is impeded by uncertainty about its clinical importance. We investigated the relationship between troponin level, coronary angiography, and all-cause mortality in real-world patients presenting with AF. Methods and Results We used National Institute of Health Research Health Informatics Collaborative data to identify patients admitted between 2010 and 2017 at 5 tertiary centers in the United Kingdom with a primary diagnosis of AF.

Long-Term Results from the IDEAL-CRT Phase 1/2 Trial of Isotoxically Dose-Escalated Radiation Therapy and Concurrent Chemotherapy for Stage II/III Non-small Cell Lung Cancer.

Purpose: The IDEAL-CRT phase 1/2 multicenter trial of isotoxically dose-escalated concurrent chemoradiation for stage II/III non-small cell lung cancer investigated two 30-fraction schedules of 5 and 6 weeks' duration. We report toxicity, tumor response, progression-free survival (PFS), and overall survival (OS) for both schedules, with long-term follow-up for the 6-week schedule.

Methods And Materials: Patients received isotoxically individualized tumor radiation doses of 63 to 71 Gy in 5 weeks or 63 to 73 Gy in 6 weeks, delivered concurrently with 2 cycles of cisplatin and vinorelbine.

A clonal expression biomarker associates with lung cancer mortality.

An aim of molecular biomarkers is to stratify patients with cancer into disease subtypes predictive of outcome, improving diagnostic precision beyond clinical descriptors such as tumor stage. Transcriptomic intratumor heterogeneity (RNA-ITH) has been shown to confound existing expression-based biomarkers across multiple cancer types. Here, we analyze multi-region whole-exome and RNA sequencing data for 156 tumor regions from 48 patients enrolled in the TRACERx study to explore and control for RNA-ITH in non-small cell lung cancer.

LightGBM: An Effective and Scalable Algorithm for Prediction of Chemical Toxicity-Application to the Tox21 and Mutagenicity Data Sets.

Machine learning algorithms have attained widespread use in assessing the potential toxicities of pharmaceuticals and industrial chemicals because of their faster speed and lower cost compared to experimental bioassays. Gradient boosting is an effective algorithm that often achieves high predictivity, but historically the relative long computational time limited its applications in predicting large compound libraries or developing predictive models that require frequent retraining. LightGBM, a recent improvement of the gradient boosting algorithm, inherited its high predictivity but resolved its scalability and long computational time by adopting a leaf-wise tree growth strategy and introducing novel techniques.

Two new species of Lafer (Carabidae, ) from China, with a key to all known Chinese species in this subgenus.

Two new species (Coleoptera, Carabidae) in the subgenus Feroperis Lafer, 1979 are described from Zhangguangcai Mountain, northeastern China: Pterostichus (Feroperis) silvestris Sun & Shi, and Pterostichus (Feroperis) maryseae Sun & Shi, Detailed descriptions and illustrations of the male endophallus and female reproductive tracts for these new species are provided, along with a key to the five known species of the subgenus in China.

BACCHUS: A randomised non-comparative phase II study of neoadjuvant chemotherapy (NACT) in patients with locally advanced rectal cancer (LARC).

Background: Chemoradiation (CRT) or short-course radiotherapy (SCRT) are standard treatments for locally advanced rectal cancer (LARC). We evaluated the efficacy/safety of two neoadjuvant chemotherapy (NACT) regimens as an alternative prior to total mesorectal excision (TME).

Methods/design: This multi-centre, phase II trial in patients with magnetic resonance imaging (MRI) defined high-risk LARC (>cT3b, cN2+ or extramural venous invasion) randomised patients (1:1) to FOLFOX + Bevacizumab (Arm 1) or FOLFOXIRI + bevacizumab (Arm 2) every 14 days for 6 cycles prior to surgery.

Acceptability of targeting social embarrassment in a digital intervention to reduce student alcohol consumption: A qualitative think aloud study.

Objective: Increasing knowledge about alcohol-related harms, changing social norms, or encouraging drinking within safe unit levels often fails to change behaviour in young people. A novel intervention called 'OneTooMany' was developed, which targets the short-term social, and potentially, embarrassing consequences of drinking alcohol. The aim of this paper was to explore its acceptability, and to determine any features that might influence its effectiveness as a means of reducing alcohol consumption.

Circulating biomarkers during treatment in patients with advanced biliary tract cancer receiving cediranib in the UK ABC-03 trial.

Background: Advanced biliary tract cancer (ABC) has a poor prognosis. Cediranib, in addition to cisplatin/gemcitabine [CisGem], improved the response rate, but did not improve the progression-free survival (PFS) in the ABC-03 study. Minimally invasive biomarkers predictive of cediranib benefit may improve patient outcomes.

Phylogenetic ctDNA analysis depicts early-stage lung cancer evolution.

The early detection of relapse following primary surgery for non-small-cell lung cancer and the characterization of emerging subclones, which seed metastatic sites, might offer new therapeutic approaches for limiting tumour recurrence. The ability to track the evolutionary dynamics of early-stage lung cancer non-invasively in circulating tumour DNA (ctDNA) has not yet been demonstrated. Here we use a tumour-specific phylogenetic approach to profile the ctDNA of the first 100 TRACERx (Tracking Non-Small-Cell Lung Cancer Evolution Through Therapy (Rx)) study participants, including one patient who was also recruited to the PEACE (Posthumous Evaluation of Advanced Cancer Environment) post-mortem study.

Clinical endpoints in trials of chemoradiation for patients with anal cancer.

This Review examines the reporting of endpoints in randomised controlled trials (RCTs) of radical chemoradiation for treatment of squamous cell carcinoma of the anus. The types, frequency, and definitions of clinical primary and secondary endpoints, and patient-reported outcome measures, reported in the methods and results sections of papers (and protocols, if available) were examined. Only six published RCTs comprising 2877 patients were identified.

Application of nanotechnology for the development of microbicides.

The vaginal route is increasingly being considered for both local and systemic delivery of drugs, especially those unsuitable for oral administration. One of the opportunities offered by this route but yet to be fully utilised is the administration of microbicides. Microbicides have an unprecedented potential for mitigating the global burden from HIV infection as heterosexual contact accounts for most of the new infections occurring in sub-Saharan Africa, the region with the highest prevalent rates.

Changing the prostate cancer management pathway: why Focal Therapy is a step forward.

Prostate Cancer (PCa) remains an exception among solid cancers since organ-sparing procedures are not considered as a standard option. Despite most men harbour low to intermediate risk disease at diagnosis, the vast majority are advised towards radical treatment. We performed a literature review to highlight and discuss why focal therapy (FT) would represent a feasible and attractive option in appropriately selected men.

Shock Index Values and Trends in Pediatric Sepsis: Predictors or Therapeutic Targets? A Retrospective Observational Study.

Background: Shock index (SI) (heart rate [HR]/systolic blood pressure [SBP]) has been used to predict outcome in both adult and pediatric sepsis within the intensive care unit (ICU). We aimed to evaluate the utility of SI before pediatric ICU (PICU) admission.

Patients And Methods: We conducted a retrospective observational study of children referred to a pediatric intensive care transport service (PICTS) between 2005 and 2011.

Metastasis as an evolutionary process.

Therapeutic advances in oncology have not fully translated to the treatment of metastatic disease, which remains largely incurable. Metastatic subclones can emerge both early and late in the life of the primary tumor. A better understanding of the genetic evolution of metastatic disease has the potential to reveal differences in the therapeutic vulnerabilities of primary and metastatic tumors, shed light on the temporal patterns of and routes to metastatic colonization, and provide insight into the biology of the metastatic process.

The Evolution of Teleophthalmology Programs in the United Kingdom: Beyond Diabetic Retinopathy Screening.

Modern ophthalmic practice in the United Kingdom is faced by the challenges of an aging population, increasing prevalence of systemic pathologies with ophthalmic manifestations, and emergent treatments that are revolutionary but dependent on timely monitoring and diagnosis. This represents a huge strain not only on diagnostic services but also outpatient management and surveillance capacity. There is an urgent need for newer means of managing this surge in demand and the socioeconomic burden it places on the health care system.

Does sex influence the diagnostic evaluation of autism spectrum disorder in adults?

It is unknown whether sex influences the diagnostic evaluation of autism spectrum disorder, or whether male and female adults within the spectrum have different symptom profiles. This study reports sex differences in clinical outcomes for 1244 adults (935 males and 309 females) referred for autism spectrum disorder assessment. Significantly, more males (72%) than females (66%) were diagnosed with an autism spectrum disorder of any subtype (x(2) = 4.

Poor oral health including active caries in 187 UK professional male football players: clinical dental examination performed by dentists.

Background: The few studies that have assessed oral health in professional/elite football suggest poor oral health with minimal data on impact on performance. The aim of this research was to determine oral health in a representative sample of professional footballers in the UK and investigate possible determinants of oral health and self-reported impact on well-being, training and performance.

Methods: Clinical oral health examination of senior squad players using standard methods and outcomes carried out at club training facilities.

Bevacizumab and Combination Chemotherapy in rectal cancer Until Surgery (BACCHUS): a phase II, multicentre, open-label, randomised study of neoadjuvant chemotherapy alone in patients with high-risk cancer of the rectum.

Background: In locally advanced rectal cancer (LARC) preoperative chemoradiation (CRT) is the standard of care, but the risk of local recurrence is low with good quality total mesorectal excision (TME), although many still develop metastatic disease. Current challenges in treating rectal cancer include the development of effective organ-preserving approaches and the prevention of subsequent metastatic disease. Neoadjuvant systemic chemotherapy (NACT) alone may reduce local and systemic recurrences, and may be more effective than postoperative treatments which often have poor compliance.

A simple method for in vivo labelling of infiltrating leukocytes in the mouse retina using indocyanine green dye.

We have developed a method to label and image myeloid cells infiltrating the mouse retina and choroid in vivo, using a single depot injection of indocyanine green dye (ICG). This was demonstrated using the following ocular models of inflammation and angiogenesis: endotoxin-induced uveitis, experimental autoimmune uveoretinitis and laser-induced choroidal neovascularization model. A near-infrared scanning ophthalmoscope was used for in vivo imaging of the eye, and flow cytometry was used on blood and spleen to assess the number and phenotype of labelled cells.