Excision pathways for keratinocyte cancers diagnosed by teledermatology: a retrospective review.

Introduction The New Zealand population has one of the highest incidences of skin cancer in the world. Hospital waiting lists for surgical excision of keratinocytic skin cancers (basal cell carcinoma and squamous cell carcinoma) are lengthy, and increasingly, excisions are undertaken in primary care. Teledermatology, in response to general practitioners' electronic referrals (e-referrals), can improve clinical communication between general practitioners and dermatologists. Aim The aim of this study was to evaluate an excision pathway for keratinocytic cancers diagnosed by teledermatology. Methods A retrospective observational descriptive review of a 3-month cohort of primary care e-referrals was undertaken. Results Three hundred and fifty eight suspected keratinocytic cancers (KCs) were diagnosed by teledermatology; histology reports confirmed KC in 201 of 267 excisions (75%). The majority (77.2%) were excised by general practitioners an average of 25 days after the dermatologist's recommendation. The rest were excised by plastic surgeons in private (3.4%) or at a public hospital (19.5%) after an average of 40 or 134 days, respectively. Discussion E-referral pathways are now widely implemented. However, the ideal workflow for skin cancer management is unknown. We have demonstrated in New Zealand that surgery can be undertaken in primary care within a month of a teledermatology diagnosis and excision recommendation. Conclusion This study reports prompt excision of KCs by general practitioners after an e-referral and a teledermatology response.

Combined spectroscopic and computational study for optimising catalyst design in hydrocarbon transformations.

Molecular interactions of hydrocarbons within the confined pores of heterogeneous catalysts can influence reaction pathways, which play a crucial role in determining the overall efficacy of catalytic transformations. We probe the interactions of n-butane with a solid-acid zeolite, mordenite, combining inelastic neutron scattering with DFT calculations. This reveals that the solid-acid sites within mordenite induce a conformer change, which could be key in designing optimised catalysts, for hydrocarbon transformations.

Food insecurity and food preparation equipment in US households: exploratory results from a cross-sectional questionnaire.

BACKGROUND: Food insecurity (FI) impacted 15.7% (5.9 million) of US households with children in 2017. These households often experience issues within one or more of the food security pillars: access, availability, utilisation or stability. An underexplored area within the pillar of utilisation that may impact FI risk is the availability of kitchen equipment in households. This exploratory project aimed to quantify household food preparation equipment ownership and use by household FI status. METHODS: An online platform (Qualtrics, Provo, UT, USA) was used to administer a questionnaire to a sample of 135 parents of children aged 11-14 years. The instrument queried sociodemographic characteristics, food preparation items owned and frequency of use of 44 items within a 6-month interval. Household FI was measured using the 18-item US Department of Agriculture, Household Food Security Survey Module with a 12-month reference period. RESULTS: Households experiencing FI (n = 39; 28.9%) owned an average of five fewer items than their food secure counterparts (n = 96, 71.1%, P < 0.001), reporting lower item ownership within each equipment category subgroup (i.e. large appliances, small appliances, food preparation utensils and cooking utensils; all P < 0.01). There were no differences between FI and food secure households in frequency of use (all P > 0.01). CONCLUSIONS: Compared to food secure households, the number of food preparation items owned was lower, although frequency of use was the same, in US households that were FI. Future projects should investigate how food equipment ownership impacts cooking behaviours, and whether households experiencing FI display behaviours to compensate for a differing set of equipment.

Successful melanoma triage by a virtual lesion clinic (teledermatoscopy).

BACKGROUND: A Virtual Lesion Clinic (VLC) using teledermatoscopy was established to improve efficiency of the melanoma referral pathway. OBJECTIVES: To assess diagnostic accuracy and to compare wait-times and costs of VLC and conventional clinics. METHODS: Patients with suspected melanoma referred from primary care into a publicly funded health system attended local skin imaging centres, rather than hospital outpatient clinics. A teledermatologist assessed each lesion choosing specialist assessment/excision, General Practitioner (GP) follow-up, to re-image in 3 months, or self-monitoring/no concern. RESULTS: 613 skin lesions in 310 patients were evaluated over 12 months. Median time between receipt of referral and attendance at the VLC was 9 days compared to 26.5 days for standard outpatient assessment. Sixty-six percent (404/613) of lesions were considered benign, and 12% (73/613) were suspicious for melanoma. Of 129 lesions excised, 98 were skin cancers including 48 histologically confirmed melanomas with one spitzoid tumour of unknown malignant potential (STUMP), i.e. one melanoma per 1.59 suspected lesions biopsied and one melanoma in every 12.8 referred to the service. There were 49 non-melanoma skin cancers (NMSC). Teledermatoscopic diagnosis of melanomas was found to have a positive predictive value (PPV) of 63%. Compared to the conventional clinic, cost reductions from running the VLC for 1 year were in excess of NZ$364,000 (or NZ$1174/patient seen). CONCLUSIONS: The VLC offered an efficient, accurate and cost effective way of processing suspected melanoma referrals to the public health system.

Morphometry of the hippocampal microvasculature in post-stroke and age-related dementias.

BACKGROUND: Optimal vascular function is vital for prevention of dementia. We hypothesized that elderly post-stroke survivors who preserve cognitive function show unperturbed cerebral microvasculature compared with those who develop dementia. METHODS: Using stereological spherical probe software, we compared the length density (Lv, cumulative vessel length per unit tissue volume) of hippocampal microvessels in post mortem brain tissue from post-stroke survivors, Alzheimer's disease (AD), vascular dementia (VaD) and normal ageing control subjects. We also assessed microvessel diameters in the same subjects. Microvessels were identified by markers of endothelial cells (glucose transporter 1; GLUT1), basement membrane (collagen IV; COL4) and smooth muscle cell α-actin (SMA). RESULTS: We found increased Lv of both GLUT1 and COL4 immunostained microvessels (P < 0.05) in the hippocampal CA1 region of post-stroke demented (PSD) and AD cases compared with post-stroke nondemented (PSND), control and VaD subjects. However, no changes were apparent in the CA2 region. We also noted significant increase in Lv in the entorhinal cortex of AD compared with PSND and PSD subjects. The mean diameter of microvessels was decreased in PSD, compared with PSND, as well as in AD and VaD compared with controls. Cumulative frequency analysis showed PSND subjects to have significantly greater proportion of microvessels with diameters, ranging from 7 to 12 µm. CONCLUSIONS: An increase in microvascular Lv in AD and PSD suggests either an increase in angiogenesis or the formation of newer microvessel loops in response to cerebral hypoperfusion. The decreased vessel diameters found in AD and VaD suggests increased vasoconstriction in dementia.

Effect of narrowband ultraviolet B phototherapy on melanocytic naevi.

BACKGROUND: Melanocytic naevi have been observed to undergo morphological changes following exposure to narrowband ultraviolet (NB-UV)B radiation. OBJECTIVES: To analyse changes in naevi exposed to NB-UVB in a large cohort of patients. METHODS: Subjects referred for phototherapy had macroscopic and dermoscopic images taken of prominent melanocytic naevi at the following time points: immediately prior to NB-UVB treatment, after 10 exposures, after 30 exposures or at the end of treatment if earlier, and 3 months after discontinuing treatment. Four dermatologists, by consensus, examined each naevus for specific clinical and dermoscopic features at each time point. The size (area) of each naevus was determined by plenimetry. RESULTS: Complete sets of images were taken for 36 out of 51 patients. The most common global dermoscopic patterns in the 440 naevi examined were reticular (50%) and globular (32%). Following NB-UVB exposure, blurring or merging of lines was observed in 45% of reticular naevi. An increase in colour intensity and in the number of dots or globules was observed in 63% of globular naevi, and 167 naevi (40%) underwent a change in size. Of these, 91/167 (54%) decreased in size, with a median area reduction of 8% (0·9-42%); while 76/167 (46%) increased in size, with a median area increase of 9% (1-76%). CONCLUSIONS: Around half of naevi exposed to a course of NB-UVB treatment undergo size or morphological changes. Naevi that enlarged tended to revert to pretreatment size 3 months after discontinuation of phototherapy.

Staging and natural history of cerebrovascular pathology in dementia.

OBJECTIVE: Most pathologic studies indicate that significant vascular changes are found in the majority of elderly persons, either alone or in association with neurodegenerative processes such as Alzheimer disease (AD) or dementia with Lewy bodies (DLB). Cumulative burden of cerebrovascular lesions can explain cognitive decline described as vascular cognitive impairment, but because there is a lack of consensus in the best way to quantify vascular pathology, the relationship between cognitive decline and cerebrovascular disease remains uncertain. We developed a rating scheme for cerebrovascular lesions using postmortem brains from patients with dementia from 2 European tertiary care memory clinics. METHODS: A total of 135 brains with a neuropathologic diagnosis of vascular dementia (VaD) (n = 26), AD + VaD (n = 39), DLB + VaD (n = 21), AD + DLB + VaD (n = 9), AD (n = 19), and DLB (n = 21) were investigated in this study. Cerebrovascular lesions were rated on large sections from the hippocampus, the temporal lobe, the frontal lobe, and basal ganglia. RESULTS: In patients with dementia, vessel wall modifications such as arteriolosclerosis or amyloid angiopathy are the most common and presumably the earliest changes. Modifications in perivascular spaces and myelin loss are the next most common. Lacunar or regional infarcts may occur as a consequence of an independent process or in the final phase of small vessel diseases. CONCLUSION: A staging system based on this conceptual model of cerebrovascular pathology could enable the neuropathologic quantification of the cerebrovascular burden in dementia. Further studies are needed to determine whether this system can be used in large-scale studies to understand clinical-cerebrovascular pathologic correlations.

Interobserver variability of teledermoscopy: an international study.

BACKGROUND: Teledermoscopy is a rapidly developing field of dermatology with studies demonstrating excellent agreement with face-to-face diagnosis. However, we are unaware of studies evaluating interobserver variability in diagnosis between dermatologists from different continents. This evaluation is important to determine the robustness of teledermoscopy and allow comparisons to be made between different studies. OBJECTIVES: To assess the interobserver diagnostic variability between five independent experienced dermatologists (A-E) in New Zealand, Australia and the U.S.A. METHODS: Images from 979 lesions from 206 patients were distributed to five dermatologists. The lesions were viewed and diagnoses recorded using MoleMap Diagnose (MoleMap, Auckland, New Zealand) software. The diagnoses were analysed for interobserver variability. RESULTS: There was excellent agreement between four of five dermatologists (A-D) for lesions that were agreed upon as melanoma (κ = 0·81-0·97) and benign naevus (κ = 0·77-0·82).The fifth dermatologist (E) made a more frequent diagnosis of atypical naevus and melanoma than the others. For nonmelanocytic lesions, there was moderate to very good agreement for seborrhoeic keratosis (κ = 0·64-0·80) and basal cell carcinoma (κ = 0·55-0·67), but poor agreement for invasive squamous cell carcinoma (SCC) (κ = 0·05-0·15). Agreement for actinic keratosis (κ = 0·32-0·67) and SCC in situ (κ = 0·15-0·32) was only moderate. When atypical and benign naevi were grouped together and actinic keratosis and SCC in situ grouped together, there was better agreement among all dermatologists. There was good ability to distinguish malignant from benign lesions (κ = 0·57-0·93). CONCLUSIONS: There was good agreement among dermatologists A-D but dermatologist E varied from the group with more frequent diagnosis of melanoma and atypical naevus. This difference could be due to different definition of terms with lack of consensus guidelines in definition of atypical naevus, lack of familiarity with the specific patient population and/or diagnostic drift.

Successful triage of patients referred to a skin lesion clinic using teledermoscopy (IMAGE IT trial).

BACKGROUND: Teledermatology is a rapidly growing field with studies showing high diagnostic accuracy when compared with face-to-face diagnosis. Teledermoscopy involves the use of epiluminescence microscopy to increase diagnostic accuracy. The utility of teledermoscopy as a triage tool has not been established. OBJECTIVES: To assess teledermoscopy as a triage tool for a hospital skin lesion clinic. METHODS: Patients referred to a dermatology skin lesion clinic were recruited. Digital and dermoscopic photographs were taken of skin lesions of concern and the patients were then seen independently face-to-face by two out of three dermatologists. The digital images were evaluated 4 weeks later, as a teledermoscopy consultation, by two of these dermatologists. The diagnosis and management from both types of consultation were compared. RESULTS: Two hundred patients with a total of 491 lesions were seen. There was excellent agreement between teledermoscopy and face-to-face diagnosis with only 12.3% of lesions having disparate diagnoses of clinical significance. Twelve of 491 (2.4%) lesions appeared to have been under-reported by teledermoscopy when compared with face-to-face diagnosis. However, when histopathology became available, only one malignant lesion had been missed (a basal cell carcinoma diagnosed as solar keratosis) by teledermoscopy. Teledermoscopy approximated 100% sensitivity and 90% specificity for detecting melanoma and nonmelanoma skin cancers. Importantly, 74% of all lesions were determined to be manageable by the general practitioner without needing to be seen face-to-face by a dermatologist. CONCLUSIONS: This use of teledermoscopy as a triage tool offers the potential to shorten waiting lists and thus improve healthcare access and delivery.

Estradiol enables cortisol to act directly upon the pituitary to suppress pituitary responsiveness to GnRH in sheep.

We have shown that cortisol infusion reduced the luteinizing hormone (LH) response to fixed hourly GnRH injections in ovariectomized ewes treated with estradiol during the non-breeding season (pituitary-clamp model). In contrast, cortisol did not affect the response to 2 hourly invariant GnRH injections in hypothalamo-pituitary disconnected ovariectomized ewes during the breeding season. To understand the differing results in these animal models and to determine if cortisol can act directly at the pituitary to suppress responsiveness to GnRH, we investigated the importance of the frequency of GnRH stimulus, the presence of estradiol and stage of the circannual breeding season. In experiment 1, during the non-breeding season, ovariectomized ewes were treated with estradiol, and pulsatile LH secretion was restored with i.v. GnRH injections either hourly or 2 hourly in the presence or absence of exogenous cortisol. Experiments 2 and 3 were conducted in hypothalamo-pituitary disconnected ovariectomized ewes in which GnRH was injected i.v. every 2 h. Experiment 2 was conducted during the non-breeding season and saline or cortisol was infused for 30 h in a cross-over design. Experiment 3 was conducted during the non-breeding and breeding seasons and saline or cortisol was infused for 30 h in the absence and presence of estradiol using a cross-over design. Samples were taken from all animals to measure plasma LH. LH pulse amplitude was reduced by cortisol in the pituitary clamp model with no difference between the hourly and 2-hourly GnRH pulse mode. In the absence of estradiol, there was no effect of cortisol on LH pulse amplitude in GnRH-replaced ovariectomized hypothalamo-pituitary disconnected ewes in either season. The LH pulse amplitude was reduced in both seasons in experiment 3 when cortisol was infused during estradiol treatment. We conclude that the ability of cortisol to reduce LH secretion does not depend upon the frequency of GnRH stimulus and that estradiol enables cortisol to act directly on the pituitary of ovariectomized hypothalamo-pituitary disconnected ewes to suppress the responsiveness to GnRH; this effect occurs in the breeding and non-breeding seasons.

Attitudes to walking and cycling among children, young people and parents: a systematic review.

BACKGROUND: Promoting walking and cycling as a part of everyday activity is seen as a strategy for tackling obesity and chronic disease. Policy needs to be based on evidence about people's views of walking and cycling as well as effects of interventions. METHODS: Studies of the views of children, young people and parents about walking and cycling were searched for systematically, and a framework analysis applied. The findings were synthesised and compared with the findings of an effectiveness review of interventions for encouraging walking and cycling as an alternative to motorised transport. RESULTS: The synthesis of views described a culture of car use, fed by a fear and dislike of local environments and parental responses that emphasised children's safety at the expense of developing their independence, despite children expressing responsible attitudes towards transport choices. Comparison with effectiveness literature found that most evaluated interventions targeted only the public's fear and dislike of local environments. CONCLUSION: Interventions need to address pedestrian and cyclist safety, perceptions of risk, and parental norms regarding children's independence.

Young people and mental health: novel methods for systematic review of research on barriers and facilitators.

This paper describes how barriers to, and facilitators of, good mental health amongst young people (11-21 years) were elucidated from a systematic review of studies of young people's views and how these barriers and facilitators were compared with effectiveness studies to identify effective and appropriate interventions, promising interventions needing further evaluation and the need for further intervention. All studies were published before 2000. No clear pattern for effectiveness emerged in terms of mental health promotion focus, the type of intervention, intervention provider or young people. Well-evaluated interventions neither always target what we know young people themselves see as important barriers to their mental health (for instance, loss of friends and family, violence and bullying) nor always build on what they see as key facilitators, particularly their preferred coping strategies. In particular, while young people see material and physical resources as major influences on their mental health, few evaluated interventions targeted these. Rigorously evaluated interventions more often addressed priorities not raised by young people themselves and populations at low risk for mental health problems. These innovative review methods can inform intervention development and evaluation in a new way based on the strengths and needs identified by the target population.

Medullary autonomic pathology in carotid sinus hypersensitivity.

AIMS: Carotid sinus hypersensitivity (CSH) is an ageing-related autonomic disorder, rarely occurring before the age of 50 years but increasing in incidence thereafter. Clinical symptoms of CSH include falls and dizziness, thought to be precipitated by dysfunctional baroreflex responses. CSH is highly prevalent in Alzheimer's disease (AD), Parkinson's disease (PD) and dementia with Lewy bodies (DLB); diseases that are associated with variable degeneration of medullary autonomic nuclei which regulate baroreflex responses. Currently, there are no descriptions of the integrity of medullary autonomic nuclei in CSH. We hypothesized medullary autonomic degeneration is found in elderly patients with CSH. METHODS: Using in vitro digital imaging, we quantified the burden of tau, amyloid beta and alpha-synuclein in autonomic nuclei of 12 patients prospectively assessed with CSH (age 83 years) compared with 14 (80 years) control subjects. RESULTS: We found increased tau (P < 0.000) accumulation in baroreflex associated nuclei, but not the hypoglossal or raphe in the CSH patients. Medullary tau accumulation was not related to the development of AD in the CSH patients. Tau was colocalized to catecholaminergic neurones and occurred in the absence of neuronal loss. We found no difference in alpha-synuclein, amyloid beta or microglial numbers between the CSH cases and controls. CONCLUSIONS: We suggest that hyperphosphorylated tau accumulation particularly in tyrosine hydroxylase containing neurones may impair central regulation of baroreflex responses in patients with CSH. Future clinic-pathological investigations should reveal whether medullary degeneration is the cause of CSH symptoms.

Individual dopaminergic neurons show raised iron levels in Parkinson disease.

OBJECTIVE: Evidence suggests that abnormal iron metabolism is associated with Parkinson disease (PD), with raised iron levels found in pathologically affected areas in PD. It is unknown if this elevated iron is actually associated with neurons or reactive glia, and we therefore addressed this issue by determining if raised iron was present in single dopaminergic neurons. METHODS: We used unfixed frozen sections from postmortem tissue of PD patients and elderly normal individuals to avoid metal contamination and translocation. Levels of iron and other elements were measured using sensitive and specific wavelength dispersive electron probe x-ray microanalysis coupled with cathodoluminescence spectroscopy in individual substantia nigra dopaminergic neurons. RESULTS: We identified raised intraneuronal iron in single defined substantia nigra neurons in PD (mean neuronal iron 2,838 vs 1,611, p < 0.0001) but not in other movement disorders such as Huntington disease. These findings were unrelated to the density of remaining neurons. CONCLUSIONS: Primary changes in neuronal iron could lead to neurodegeneration in Parkinson disease.

Medullary microvessel degeneration in multiple system atrophy.

Multiple system atrophy (MSA) is a rare and fatal early-onset autonomic disorder which is characterised by Parkinsonism and orthostatic hypotension (OH). The pathophysiology of MSA is not fully understood but key features include the depletion of medullary autonomic neurons and presence of glial cellular inclusions. We hypothesise that the degeneration of medullary autonomic microvessels is an additional finding in MSA. Using digital pathology we quantified basement membrane collagen (Coll IV), smooth muscle actin (alpha-actin) and endothelial glucose transporter (Glut 1) expression in medullary autonomic nuclei of 8 MSA and 8 OH cases, compared with 12 controls with no autonomic dysfunction. We found decreased Coll IV (p=0.000) and Glut 1 (p=0.000) but not alpha-actin expression, in medullary autonomic nuclei of MSA, but not OH cases compared with control subjects. Medullary microvessel degeneration in MSA may be secondary to the primary neuro-glial pathogenesis of the disorder, and could accelerate its ageing-related progression.

Does the UK government's teenage pregnancy strategy deal with the correct risk factors? Findings from a secondary analysis of data from a randomised trial of sex education and their implications for policy.

BACKGROUND: Much of the UK government's 1999 report on teenage pregnancy was by necessity based on rather old or non-longitudinal research. AIM: To examine the associations between risk factors identified in the report and pregnancy at or before age 16 years among young women and partners of young men using the more recent data. RESULTS: Socioeconomic disadvantage, being born to a teenage mother, expectation of being a teenage parent, low educational expectations and various other behaviours are potential risk factors for teenage pregnancy, as suggested by unadjusted analyses. Those who cited school as providing information on sex had a reduced risk of pregnancy at or before age 16 years, as did girls reporting easy communication with parent or guardian at baseline. Various measures of low sexual health knowledge were not associated, in either adjusted or unadjusted analyses, with increased risk of pregnancy at or before age 16 years among boys or girls. CONCLUSIONS: A focus on many of the risk factors identified in the 1999 report is supported herein. It is suggested that knowledge may not be an important determinant, but that relationships with parents and school, as well as expectations for the future, may have important influences on teenage pregnancy. The analysis also provides new insights into risk factors for pregnancies among the partners of young men.

Young people and physical activity: a systematic review matching their views to effective interventions.

A systematic review was conducted to examine the barriers to, and facilitators of, physical activity among young people (11-16 years). The review focused on the wider determinants of health, examining community- and society-level interventions. Four trials and 16 studies of young people's views were included. Evidence for the effectiveness of the interventions was limited, with some suggestions of improvements in knowledge and possible differences according to gender. Young women in particular identified barriers to physical activity associated with certain ways of providing physical education in schools. Young people in general identified a need for increased choice and facilities within the community and emphasized physical activity's social side. Some of the barriers and facilitators identified by young people had been addressed by 'soundly evaluated' effective interventions but significant gaps were identified where no evaluated interventions appear to have been published (e.g. initiatives explicitly addressing gender issues or the combination of sport and other leisure activities), or where there were no soundly evaluated interventions. Rigorous evaluation is required particularly to assess initiatives that address the limited practical and material resources that young people identify as barriers to physical activity.

Effects of NOS inhibition on the cardiopulmonary system and brain microvascular markers after intermittent hypoxia in rats.

We previously demonstrated that rats subjected to intermittent hypoxia (IH) by exposure to 10% O(2) for 4 h daily for 56 days in a normobaric chamber, developed pulmonary hypertension, right ventricular hypertrophy and wall-thickening in pulmonary arterioles, compared with normoxic (N) controls. These changes were greater in rats subjected to continuous hypoxia (CH breathing 10% O(2) for 56 days). Cerebral angiogenesis was demonstrated by immunostaining with glucose transporter 1 (GLUT1) antibody, in viable vessels, in CH and to a lesser degree in IH. In this study, adult Wistar rats were subjected to the same hypoxic regimes and given the nitric oxide synthase (NOS) inhibitor N(6)-nitro-L-arginine methyl ester (L-NAME) in drinking water (NLN, IHLN and CHLN regimes) to induce hypertension. There was significant systemic hypertension in NLN and IHLN rats, compared with N and IH, but surprisingly not in CHLN compared with CH. Hematocrit rose in all hypoxic groups (up to 79% in CHLN). There was no significant pulmonary hypertension in IHLN versus NLN rats, although there was asymmetric wall thickening in pulmonary arterioles. Cerebral GLUT1 immunoreactivity increased with L-NAME, with or without hypoxia, especially in CHLN rats, but conspicuously there was no evidence of angiogenesis in brains of IHLN compared with NLN rats. NOS blockade may attenuate the cerebral and pulmonary vascular changes of IH while augmenting cerebral angiogenesis in continuous hypoxia. However, whether cerebral effects are due to systemic hypertension or changes in cerebral nitric oxide production needs to be evaluated.