Wordsley Hospital

Relapse and treatment resistance are common in children with high-risk neuroblastoma, and novel therapies are needed. Conventional drug discovery is slow, expensive, often fails in practice, and consequently falls short in addressing pediatric and rare conditions. In such instances, drug repurposing is a promising strategy. Here, we used two independent in silico prediction tools including machine learning to identify approved drugs for repurposing against neuroblastoma. The combination of statins and phenothiazines showed strong synergistic effects in human neuroblastoma organoids, decreased tumor growth, and prolonged survival in MYCN-amplified neuroblastoma patient-derived xenografts. The drug combination altered cholesterol metabolism through two different mechanisms and induced a phenotypic change toward an adrenergic state in vitro, which was associated with enhanced chemosensitivity. Integration of the drug combination into standard-of-care chemotherapy regressed tumors and prolonged survival in chemoresistant patient-derived xenografts. Thus, a combination of safe and approved medications added to standard-of-care chemotherapy outperforms chemotherapy alone in chemoresistant neuroblastoma.

Abstract Glass fibre reinforced plastic (GRP) or glass reinforced epoxy (GRE) piping is being increasingly used in firewater and cooling water duties where seawater is used. These composite materials are especially suited for these applications due to their excellent corrosion resistance to seawater, but they do have some special design requirements that are different to metallic piping. One of these requirements relates to the design of the bolted flange connections. Unlike metallic piping materials, GRP and GRE materials are not ductile and the strength properties can degrade over time when the material is under stress. Partly for this reason, piping flanges are generally specified as full face rather than raised face to reduce the bending stresses due to bolting loads. Consequently, relatively “soft” gasket materials are also generally specified as they do not require a high contact pressure that is more easily attained with a raised face flange to produce a good seal and prevent leakage. A common requirement in stress analysis of piping systems is to check the effect of bending moments and forces from the piping system on the ability of the flanged joint to prevent leakage. This assessment is built into pipe stress software using either the equivalent pressure method and comparing this to the flange rated pressure or to the “ASME III NC 3658 method”. However, neither method is directly applicable for full face flanges. This study investigates appropriate criteria for the assessment of bending moments and forces from the piping system on bolted flanged joints in GRP piping. Another important variable is the initial flange bolt tension. Higher bolt pretension reduces the likelihood of leakage but for GRP flanges, limits are required on bolt pretension to avoid damage such as cracking of the GRP flange material. Despite the lower bolt pretensions, GRP full face flanges together with soft gaskets can be shown to have good resistance to external piping loads.

Accessible summary • We wanted to find out more information about adults with profound and multiple learning disabilities who lived in our area. • We carried out a survey (audit) using information from the local Community Teams. • We found 61 people. Many of these people had two or more disabilities e.g. physical disability, hearing problems, epilepsy, problems with eating and drinking. • We have set up a multidisciplinary team to work with this group of people. • We have made a register to keep information up to date. • We want to highlight the very special needs of this group of people and make sure they are given a good service. Summary An audit was carried out to gain an overview of the profound and multiple learning disabilities (PMLD) population in a local health trust to inform current and future service provision. An overview of the issues faced in developing clear defining criteria is presented. Published definitions of PMLD were used to identify clients from data held on the Special Needs Register (SNR – a data base of people with learning disabilities known to health and social services departments). Information obtained was cross checked with community teams and other professional service records to identify any further individuals who may meet criteria for PMLD. Existing information from individual case notes was then audited to confirm the clients identified meet the criteria for PMLD. The audit identified 61 adults with PMLD; all have complex needs and multiple health care requirements. Eighty-three per cent had two or more disabilities in addition to profound intellectual impairment. Twenty-nine per cent were reported as having problems with dysphagia. People with PMLD should be given priority for health action plans, particularly vision and hearing screening. The audit also needs to be extended to include younger people in transition to adult services. A register of clients with PMLD needs to be established and maintained as part of the SNR register.

Non-puerperal uterine inversion is an extremely rare entity, which many gynaecologists would never come across in their lifetime. Diagnosis can be difficult. Our patient was a 91-year-old lady who presented with profuse vaginal bleeding. Hysteroscopy was unsuccessful as the cervix was completely replaced by a friable growth. A total abdominal hysterectomy and bilateral salpingo-oophorectomy was planned as a palliative measure to stop bleeding. Uterine inversion was suspected for the first time at laparotomy and confirmed after dissecting the hysterectomy specimen, which revealed both tubes and ovaries lying inside the inverted uterus. Histology showed a malignant mixed mullerian tumour of the uterus.

Historical aspects of cicatrial cancer are presented and 18 cases of cicatrial cancer reviewed. The incidence of cicatrial cancer is increasing, paralleling other skin tumours. Survival is better than many series have suggested. Prevention and treatment is discussed in relation to the biological behaviour of scars and their tumours. A high index of suspicion for chronic non-healing lesions in scarred areas will increase survival.

Abstract This paper describes the characteristics of and development plans for the PY-1 concession, a gas reservoir contained in a naturally-fractured granite formation. Over a several-year period, exploration and delineation wells were drilled offshore India. The paper covers all aspects of the integrated geoscience/engineering development study, including seismic, core and fracture analyses, well logging, well testing, and reservoir simulation. In addition, we include the offshore facilities, pipeline and onshore compression plans. The development plan was prepared by a team of engineers and geoscientists made up of both operating company personnel and contract and consulting personnel. The result of the study is a development plan for a granite reservoir. We conclude that highly-fractured granite formations should not be overlooked as potential reservoirs. This granite reservoir should provide a steady gas supply to any one of several commercial manufacturing facilities planned for the area.

Journal Article Bullous eruption due to Cimex lecticularis Get access Tharakaram Tharakaram Department of Dermatology, Wordsley Hospital, Stourbridge, UK Tharakaram Wordsley Hospital, Stream Road, Stourbridge DY8 5QX, UK. Tel/Fax: + 44 1384 244512. Search for other works by this author on: Oxford Academic Google Scholar Clinical and Experimental Dermatology, Volume 24, Issue 3, 1 May 1999, Pages 241–242, https://doi.org/10.1046/j.1365-2230.1999.00467.x Published: 01 May 1999