The association of smoking and socioeconomic status on cutaneous melanoma: a population-based, data-linkage, case-control study.

BACKGROUND: Previous studies have identified an inverse association between melanoma and smoking; however, data from population-based studies are scarce. OBJECTIVES: To determine the association between smoking and socioeconomic (SES) on the risk of development of melanoma. Furthermore, we sought to determine the implications of smoking and SES on survival. METHODS: We conducted a population-based case-control study. Cases were identified from the Welsh Cancer Intelligence and Surveillance Unit (WCISU) during 2000-2015 and controls from the general population. Smoking and SES were obtained from data linkage with other national databases. The association of smoking status and SES on the incidence of melanoma were assessed using binary logistic regression. Multivariate survival analysis was performed on a melanoma cohort using a Cox proportional hazard model using survival as the outcome. RESULTS: During 2000-2015, 9636 patients developed melanoma. Smoking data were obtained for 7124 (73·9%) of these patients. There were 26 408 controls identified from the general population. Smoking was inversely associated with melanoma incidence [odds ratio (OR) 0·70, 95% confidence interval (CI) 0·65-0·76]. Smoking was associated with an increased overall mortality [hazard ratio (HR) 1·30, 95% CI 1·09-1·55], but not associated with melanoma-specific mortality. Patients with higher SES had an increased association with melanoma incidence (OR 1·58, 95% CI 1·44-1·73). Higher SES was associated with an increased chance of both overall (HR 0·67, 95% CI 0·56-0·81) and disease-specific survival (HR 0·69, 95% CI 0·53-0·90). CONCLUSIONS: Our study has demonstrated that smoking appeared to be associated with reduced incidence of melanoma. Although smoking increases overall mortality, no association was observed with melanoma-specific mortality. Further work is required to determine if there is a biological mechanism underlying this relationship or an alternative explanation, such as survival bias. What's already known about this topic? Previous studies have been contradictory with both negative and positive associations between smoking and the incidence of melanoma reported. Previous studies have either been limited by publication bias because of selective reporting or underpowered. What does this study add? Our large study identified an inverse association between smoking status and melanoma incidence. Although smoking status was negatively associated with overall disease survival, no significant association was noted in melanoma-specific survival. Socioeconomic status remains closely associated with melanoma. Although higher socioeconomic populations are more likely to develop the disease, patients with lower socioeconomic status continue to have a worse prognosis.

Gel network shampoo formulation and hair health benefits.

OBJECTIVE: The objective of this work was to create a shampoo formula that contains a stable ordered gel network structure that delivers fatty alcohols inside hair. METHODS: X-ray diffraction (SAXS and WAXS), SEM and DSC have been used to confirm formation of the ordered Lß gel network with fatty alcohol (cetyl and stearyl alcohols) and an anionic surfactant (SLE1S). Micro-autoradiography and extraction methods using GC-MS were used to confirm penetration of fatty alcohols into hair, and cyclic fatigue testing was used to measure hair strength. RESULTS: In this work, evidence of a stable Lß ordered gel network structure created from cetyl and stearyl alcohols and anionic surfactant (SLE1S) is presented, and this is confirmed via scanning electron microscopy images showing lamella layers and differential scanning calorimetry (DSC) showing new melting peaks vs the starting fatty alcohols. Hair washed for 16 repeat cycles with this shampoo showed penetration of fatty alcohols from the gel network into hair as confirmed by a differential extraction method with GC-MS and by radiolabelling of stearyl alcohol and showing its presence inside hair cross-sections. The gel network role in delivering fatty alcohol inside hair is demonstrated by comparing with a shampoo with added fatty alcohol not in an ordered gel network structure. The hair containing fatty alcohol was measured via the Dia-stron cyclic fatigue instrument and showed a significantly higher number of cycles to break vs control. CONCLUSIONS: The formation of a stable gel network was confirmed in the formulated shampoo, and it was demonstrated that this gel network is important to deliver cetyl and stearyl alcohols into hair. The presence of fatty alcohol inside hair was shown to deliver a hair strength benefit via cyclic fatigue testing.

Multifocal capillary malformations in an older, asymptomatic child with a novel RASA1 mutation.

Multifocal capillary malformation (CM) is the cardinal feature of patients with RASA1 mutations. These CMs are 'red flags', signalling the possible association with an arteriovenous malformation (AVM) or an arteriovenous fistula (AVF). We report an 8-year-old boy who presented with > 20 CMs, who was found to have a novel mutation in the RASA1 gene. Radiological screening of children with RASA1 mutations is not standardized, and we elected to carry out baseline magnetic resonance imaging of the brain and spine in our case, which gave normal results. We discuss the recent literature and our approach in the management of such a case.

The incidence of non-melanoma skin cancer in the UK and the Republic of Ireland: a systematic review.

BACKGROUND: Basal cell carcinoma (BCC) and cutaneous squamous cell carcinoma (cSCC) remain the most prevalent malignancies, contributing a higher workload to cancer registries than all cancers combined. The nature of skin cancers in addition to current coding methods employed by registries give a skewed representation of the workload. OBJECTIVES: A comprehensive search examining the incidence of BCC and/or cSCC at a regional or national level in the UK and Ireland was devised. Standardisation methods were grouped to permit comparison, and a bias assessment tool was employed. MATERIALS & METHODS: Sixteen UK and Republic of Ireland epidemiological studies on BCC/cSCC over a 48-year period were compiled, examining incidence, trends and emerging risk factors. RESULTS: Incidence of BCC within the UK is increasing annually by up to 4%, with rates in Wales increasing by up to 6.6% and 1.6% annually for BCC and cSCC, respectively. Inverse relationships are noted between BCC/cSCC and social deprivation. Although the elderly remain the most at risk, the 30-49 age group have illustrated growth rates of approximately 4%. CONCLUSION: This review outlines increasing incidence in the UK with higher rates noted in Wales, the Southeast, West and Central regions. Incidence rates are higher amongst the least socially deprived and an increasing incidence amongst younger age groups was found, however further trend analysis is required. A more comprehensive data collection method within registries is necessary to ensure accurate representation and fluid comparison. Service planning and public awareness campaigns must be implemented to prevent overwhelming future services.

Latinx Patients' Perceptions of Culturally Sensitive Health Care and their Association with Patient Satisfaction, Patient-Provider Communication, and Therapeutic Alliance.

Latinx in the USA experience disparities in morbidity and mortality when compared to their non-Hispanic White counterparts. Patient-centered culturally sensitive health care (PC-CSHC) has been deemed a best practice approach to alleviate and eliminate these disparities. However, literature on how Latinx patients perceive their care and what indicators of PC-CSHC may be most related to treatment outcomes is limited. This study collected data from 81 adult Latinx participants who had been admitted to an inpatient care unit to understand the following: (a) their perception of their providers' PC-CSHC in three different areas: Competence/Confidence, Sensitivity/Interpersonal, and Respect/Communication; (b) whether there are differences between English- and Spanish-speaking Latinx patients in their perception of their providers' PC-CSHC; and (c) whether these PC-CSHC indicators were associated to patient satisfaction, patient-provider communication, and therapeutic alliance. Participants were mostly male, older than 55 years of age, and working or lower class, with English as their primary language. Results showed that patients rated their providers' Competence (M = 3.57, SD = .46) higher than both Sensitivity, t(68) = .04, p = .04, (M = 3.49, SD =.54), and Respect, t(53) = 2.765, p = .008, (M = 3.38, SD = .57). English-speaking Latinx were overall less satisfied with their providers than Spanish-speaking Latinx, in particular in their communication. Finally, higher provider cultural sensitivity appears to be a predictor of patient satisfaction, patient-provider communication, and working alliance. Implications for refining provider trainings to treat this vulnerable and understudied (i.e., Latinx) population are discussed.

Undergraduate occupational medicine tuition in UK schools of medicine.

AIMS: To assess any recent change in the quantity of teaching of occupational medicine (OM) in UK undergraduate medical curricula, and to compare these results with those obtained in previous years. METHODS: A questionnaire survey designed to capture information on the teaching of OM to undergraduates in all medical schools listed in the UK Universities and Colleges Admissions Service prospectus for 2008-09. RESULTS: Twenty-one of 32 (66%) UK medical schools returned a completed questionnaire. A comparison of results from this survey, with previous surveys, of teaching of OM to undergraduates in the UK showed that fewer schools now provide lectures, project work or ward-based tuition in this subject, than previously. In contrast to previous surveys, workplace visits were not undertaken by any institution. Only three (15%) of the schools setting an examination question related to OM also had a syllabus or explicit learning outcomes. More schools reported incorporating OM teaching within the teaching of other subjects. CONCLUSIONS: Despite the increasing recognition of the impact and value of work on health and the growing evidence base to support work as a means of enhancing health, medical schools fall far short of a comprehensive programme of teaching in this important subject area. This may result in doctors being poorly prepared to recognize and diagnose occupational diseases adequately, and poorly equipped to support their patients in, for example, return to work, rehabilitation or providing advice on fitness to work.

A genetically determined insertion/deletion related polymorphism in human T cell receptor beta chain (TCRB) includes functional variable gene segments.

Polymorphism in the human T cell receptor beta chain (TCRB) gene complex includes haplotypes with different numbers of TCRBV genes. An insertion/deletion related polymorphism (IDRP) in the human TCRBV region was found to involve TCRBV gene segments. Inserted TCRB haplotypes contain an additional 21.5 kb in which three TCRBV genes are encoded, members of the TCRBV7, TCRBV9, and TCRBV13 families. Two TCRBV gene segments were present only in inserted haplotypes; one of these, TCRBV7S3, is a functional gene and the other, TCRBV9S2(P), is a pseudogene because of an inframe termination colon. In addition, inserted haplotypes contain two identical copies of the TCRBV13S2 gene, whereas deleted haplotypes have only one copy. Deleted haplotypes could be subdivided into two types, deleted*1 and deleted*2, on the basis of sequence variations in TCRBV6S7 and TCRBV13S2 genes. Both deleted*1 and deleted*2 haplotypes contained the same number of TCRBV genes; both contain 60 genes of which 50 are functional, whereas, inserted haplotypes contained 63 genes of which 52 are functional. Comparisons of inserted region sequences with the homologous region in a deleted haplotype, and with sequences surrounding related TCRBV genes, revealed patterns of similarity that suggest insertion as well as deletion events have occurred in the evolution of the TCRBV gene complex. These data indicate that the genomic TCR repertoire is expanded in individuals who have inserted TCRBV haplotypes. The presence of additional TCRBV genes or, alternatively, the absence of certain TCRBV genes may have an impact upon immune responses and susceptibility to autoimmune diseases.

An investigation to ascertain whether or not time pressure influences the accuracy of final year student radiographers in abnormality detection when interpreting conventional appendicular trauma radiographs: A pilot study.

INTRODUCTION: There is an increasing demand on diagnostic imaging departments, a shortage of radiologists, and a backlog of images requiring a report across several trusts in the UK. A negative impact on performance can result in significant outcomes for the patient. The aim of this study is to ascertain whether decisions made under time pressure will affect the accuracy of the interpretation of conventional radiographs. METHODS: Final year undergraduate diagnostic radiography students were recruited [n = 21] and separated into three groups of seven at random, assigning time limits per image for a set of normal and abnormal conventional appendicular radiographs; 15 s (high pressure), 30 s (moderate pressure) and unlimited time (low pressure). Each image was assessed, and answers were recorded as normal or abnormal with an approximate location of the pathology. RESULTS: The ANOVA test revealed no statistical significance amongst results. The mean accuracy was highest in the 15 s group (82.86%) and lowest in the unlimited time group (74.52%). The results also demonstrated a decrease in accuracy with increased image review times within the unlimited time group; with the quickest participant achieving 88.33% and the slowest, 56.67%. CONCLUSION: The results demonstrated no statistical significance. However, it is recommended to conduct a similar study using sufficient reporting practitioners to enable direct parallels to be drawn with statistical significance. IMPLICATIONS FOR PRACTICE: The results signify an importance for imaging departments to manage the number of staff and their workload. Subsequently, this aims to ensure reporting practitioners work at their optimum stress level for efficient work performance.

The Human Papillomavirus as a Common Pathogen in Oropharyngeal, Anal and Cervical Cancers.

The burden of human papillomavirus (HPV)-related cancers worldwide is significant. Although the incidence of cervical cancer is decreasing due to cervical screening programmes, the incidences of oropharyngeal, anal and vulval cancers are increasing. The introduction of HPV vaccination programmes in many countries has had an impact on HPV infection rates but due to the time-lag from initial HPV infection to the development of invasive carcinoma, the impact on the incidence of HPV-related cancer will take more time to become evident. This review explores the common aspects of HPV-related cancers and how they differ from their HPV-negative counterparts, both clinically and molecularly. It also covers the implications this has on future treatment strategies, including the possible role of immunotherapy.

Management of regional metastatic disease in cutaneous malignancy of the head and neck. 3. Merkel cell carcinoma.

This is the third of three articles that give an overview of the current evidence for management of the neck and parotid in patients with cutaneous cancers of the head and neck. In this paper we discuss Merkel cell carcinoma (MCC) and review the latest evidence for management of the regional nodes.

When to respond? And how much? Temporal control and response output on mixed-fixed-interval schedules with unequally probable components.

Rats were trained on mixed-fixed-interval (FI) schedules, with component FIs of 30 and 60s. The probability of reinforcement according to FI 30s varied between conditions, across values of 0.1, 0.3, 0.5, 0.7 and 0.9. When response rate in the 60s intervals was measured, separate response peaks, one close to 30s, the other at 60s, could be identified when the probability of reinforcement at 30s was 0.3 or greater. Nonlinear regression found that the location of the earlier peak was always close to 30s, that the coefficient of variation of the response functions at 30 and 60s were unaffected by reinforcement probability, but that the 30s component appeared to be timed slightly more precisely than the 60s one. Response rate at around 30s increased with increasing probability of reinforcement according to FI 30s, but responding at 60s was unaffected by reinforcement probability. The data are discussed with respect to a number of contemporary models of animal timing (scalar expectancy theory, the Behavioural Theory of Timing and the Learning to Time model), and a recent account of response output on FI-like schedules.

Conserved cis-elements in the Xenopus red opsin promoter necessary for cone-specific expression.

The long-wavelength sensitive (red) opsin genes encode proteins which play a central role in daytime and color vision in vertebrates. We used transgenic Xenopus to identify 5' cis-elements in the red cone opsin promoter necessary for cone-specific expression. We found a highly conserved extended region (-725 to -173) that was required for restricting GFP transgene expression to cones. We further identified a short element (5'-CCAATTAAGAGAT-3') highly conserved amongst tetrapods, including humans, necessary to restrict expression to cones in the retina. These results identify novel conserved elements that regulate spatial expression of tetrapod red cone opsin genes.

Diffusion of Charged Species in Liquids.

In this study the laws of mechanics for multi-component systems are used to develop a theory for the diffusion of ions in the presence of an electrostatic field. The analysis begins with the governing equation for the species velocity and it leads to the governing equation for the species diffusion velocity. Simplification of this latter result provides a momentum equation containing three dominant forces: (a) the gradient of the partial pressure, (b) the electrostatic force, and (c) the diffusive drag force that is a central feature of the Maxwell-Stefan equations. For ideal gas mixtures we derive the classic Nernst-Planck equation. For liquid-phase diffusion we encounter a situation in which the Nernst-Planck contribution to diffusion differs by several orders of magnitude from that obtained for ideal gases.

Non-melanoma skin cancer: United Kingdom National Multidisciplinary Guidelines.

This is the official guideline endorsed by the specialty associations involved in the care of head and neck cancer patients in the UK. This paper provides consensus recommendations on the management of cutaneous basal cell carcinoma and squamous cell carcinoma in the head and neck region on the basis of current evidence. Recommendations • Royal College of Pathologists minimum datasets for NMSC should be adhered to in order to improve patient care and help work-force planning in pathology departments. (G) • Tumour depth is of critical importance in identifying high-risk cutaneous squamous cell carcinoma (cSCC), and should be reported in all cases. (R) • Appropriate imaging to determine the extent of primary NMSC is indicated when peri-neural involvement or bony invasion is suspected. (R) • In the clinically N0 neck, radiological imaging is not beneficial, and a policy of watchful waiting and patient education can be adopted. (R) • Patients with high-risk NMSC should be treated by members of a skin cancer multidisciplinary team (MDT) in secondary care. (G) • Non-infiltrative basal cell carcinoma (BCC) <2 cm in size should be excised with a margin of 4-5 mm. Smaller margins (2-3 mm) may be taken in sites where reconstructive options are limited, when reconstruction should be delayed. (R) • Where there is a high risk of recurrence, delayed reconstruction or Mohs micrographic surgery should be used. (R) • Surgical excision of low-risk cSCC with a margin of 4 mm or greater is the treatment of choice. (R) • High-risk cSCC should be excised with a margin of 6 mm or greater. (R). • Mohs micrographic surgery has a role in some high-risk cSCC cases following MDT discussion. (R) • Delayed reconstruction should be used in high-risk cSCC. (G) • Intra-operative conventional frozen section in cSCC is not recommended. (G) • Radiotherapy (RT) is an effective therapy for primary BCC and cSCC. (R) • Re-excision should be carried out for incompletely excised high-risk BCC or where there is deep margin involvement. (R) • Incompletely excised high-risk cSCC should be re-excised. (R) • Further surgery should involve confirmed marginal clearance before reconstruction. (R) • P+ N0 disease: Resection should include involved parotid tissue, combined with levels I-III neck dissection, to include the external jugular node. (R) • P+ N+ disease: Resection should include level V if that level is clinically or radiologically involved. (R) • Adjuvant RT should include level V if not dissected. (R) • P0 N+ disease: Anterior neck disease should be managed with levels I-IV neck dissection to include the external jugular node. (R) • P0 N+ posterior echelon nodal disease (i.e. occipital or post-auricular) should undergo dissection of levels II-V, with sparing of level I. (R) • Consider treatment of the ipsilateral parotid if the primary site is the anterior scalp, temple or forehead. (R) • All patients should receive education in self-examination and skin cancer prevention measures. (G) • Patients who have had a single completely excised BCC or low-risk cSCC can be discharged after a single post-operative visit. (G) • Patients with an excised high-risk cSCC should be reviewed three to six monthly for two years, with further annual review depending upon clinical risk. (G) • Those with recurrent or multiple BCCs should be offered annual review. (G).

Reaction of Tris with aldehydes. Effect of Tris on reactions catalyzed by homoserine dehydrogenase and glyceraldehyde-3-phosphate dehydrogenase.

Tris buffer was observed to produce an apparent inhibition of the homoserine dehydrogenase (EC 1.1.1.3)-catalyzed reduction of aspartic beta-semialdehyde and an apparent inhibition of the glyceraldehyde phosphate dehydrogenase (EC 1.2.1.9)-catalyzed oxidation of glyceraldehyde 3-phosphate. In each case, the apparent inhibition was found to be due to a lowering of the substrate concentration as a result of a reversible reaction between the free base form of Tris and the substrate, an aldehyde. The product of the reaction was tentatively identified as an imine on the basis of its spectral properties. The inhibition of these two enzymatic reactions by Tris was employed to investigate the kinetics of the reaction of Tris with their substrates. Assuming that these aldehydes exist entirely as the free aldehyde in aqueous solution, equilibrium constants of 369 +/- 12M-1 and 68 +/- 1.5M-1 were determined at 25 degrees C for the reaction of the free base form of Tris with glyceraldehyde 3-phosphate and asparitic beta-semialdehyde, respectively. Correcting for the existence of the hydrated form of glyceraldehyde 3-phosphate in aqueous solution, an equilibrium constant of 1.1-10(4) M-1 was obtained for the reaction of this aldehyde with the free base form of Tris. Forward and reverse direction rate constants for the reaction of Tris with glyceraldehyde 3-phosphate were determined at pH 7.45 and pH 8.5, and both were found to be pH-dependent.

Stage I-II pediatric Hodgkin's disease: long-term follow-up demonstrates equivalent survival rates following different management schemes.

The results of treatment of 171 children with stage I-II Hodgkin's disease from two institutions with differing approaches to management have been analyzed. At the Stanford University Medical Center/Children's Hospital at Stanford (SUMC/CHaS), pathologic staging followed by extended-field radiation alone or involved-field radiation plus combination chemotherapy have been cardinal to the management policy. At St Bartholomew's Hospital/The Hospital for Sick Children at Great Ormond Street (Barts/GOS), clinical staging only has been used over the last 10 years, and involved/regional-field radiotherapy used as the treatment of choice rather than extended-field radiotherapy. Some children at each institution received combined modality therapy as primary management. Relapse among children with stage I disease was a more frequent occurrence in the Barts/GOS series than in the SUMC/CHaS group. However, the survival rates from the two centers are identical, 91% at 10 years. The following scientific-philosophic question is asked: Should one maximally stage and treat all children to increase the likelihood of a high freedom from relapse (FFR; cure) rate, or is it acceptable to minimize the initial staging and treatment, realizing that a proportion of patients will fail and require salvage/rescue therapy? With the awareness of morbidity from pathologic staging and aggressive treatment, and the favorable survival data reported from specialized centers using differing approaches, treatment strategies should be directed toward the long-term goal of cure of disease with maximal quality of life. A multidisciplinary management philosophy undertaken at a center with extensive experience in pediatric Hodgkin's disease is important to achieving this goal.

Hepatic enzyme induction patterns and phenothiazine side effects.

D-Glucaric acid excretion was followed in psychotic patients treated with phenothiazines for 12 days and in a control group of subjects who had no psychiatric disease. About half the psychiatric patients had a treatment-related rise in D-glucaric acid excretion compatible with enzyme induction. These patients had fewer and less severe neurologic side effects than those who did not have a significant rise in urinary D-glucaric acid levels. It is concluded that individual differences in metabolism of phenothiazines may in part account for the variability in clinical response to these drugs.

DNA damage by drugs and radiation: what is important and how is it measured?

DNA is the most important target for drug and radiation induced cell killing. The mode of cell killing by cytotoxic drugs and radiation has been derived by correlating the type and quantity of DNA damage induced with lethality. Cytotoxic drugs can be classified by their main mode of action, while ionising radiation causes a range of lesions with the DNA double-strand break (dsb) being the most significant. Strand-breaks are measured from the reduction in the size of DNA molecules following treatment. Molecule size can be derived from the rate that DNA fragments sediment when centrifuged, elute through filters or migrate under electrophoresis. The effect of strand-breaks on DNA loop supercoiling allow a sensitive assay of DNA damage. Specific assays for base damage and drug adducts include changes in chromatographic mobility or binding by specific antibodies. By comparing the levels of damage in the genome overall with damage in specific gene targets, regions susceptible to damage induction, and varying in repair efficiency, have been revealed.

Molecular assays of radiation-induced DNA damage.

There is a need for assays of DNA damage in many areas of laboratory research applied to radiation therapy, in order to understand the molecular processes involved in cell killing by ionising radiation and to predict in vivo response. Assays exist which measure many types of DNA damage following ionising radiation. From studies of the dose-response relationships for different types of damage, the double-strand break (dsb) has been shown to be the most significant lesion. Assays for DNA dsb have been of low sensitivity, such that supralethal doses of radiation had to be used in order to study dsb induction or repair. New assays, such as pulsed-field gel electrophoresis, are sensitive to dsb in a dose range relevant to cell survival. In addition, these assays can assess the distribution of dsb in different parts of the genome and determine heterogeneity of damage induction and repair. Assays which measure the effects of strand breaks on DNA complexed with nuclear matrix can reveal features of chromatin organisation and their influence on cellular radiosensitivity.