Factors associated with survival after early at-home NIV initiation in ALS patients.

BACKGROUND: The initiation of early non-invasive ventilation (NIV) often involves a careful balance between tolerance and effectiveness. In amyotrophic lateral sclerosis (ALS) patients, the establishment of a strategy, including the decision to focus on adhering to a cut-off, setting specific targets, or correcting all events, is crucial. OBJECTIVE: To identify factors at 1 month after early at-home NIV initiation that are associated with improved survival in ALS patients. We explored the impacts of adherence (ADH), quality of treatment, and NIV parameters at 1 month after early at-home NIV initiation on patient survival. METHODS: We conducted a retrospective study of 184 ALS patients at the Bordeaux ALS Centre for whom NIV was initiated between September 2017 and June 2021, and we collected data for a minimum period of 2 years after the last patient included. The primary outcome was the risk of death according to baseline characteristics of our population and the NIV parameters and monitoring during the early NIV initiation period. The secondary outcomes were association with NIV ADH during the early NIV initiation period on prognosis, and NIV ADH cut-off for good versus poor prognosis. RESULTS: Among the 178 ALS patients analysed, we found that quality of NIV treatment and device settings did not significantly influence prognosis. However, low ADH was significantly associated with a higher risk of death. The use of NIV for > 5 h/day during the early NIV initiation period was linked to a decreased risk of death [hazard ratio = 0.4; 95% confidence interval: 0.27-0.9]. CONCLUSION: The use of NIV for > 5 h/day during the early NIV initiation period was associated with increased survival.

Metabolic Reprogramming in Amyotrophic Lateral Sclerosis.

Mitochondrial dysfunction in the spinal cord is a hallmark of amyotrophic lateral sclerosis (ALS), but the neurometabolic alterations during early stages of the disease remain unknown. Here, we investigated the bioenergetic and proteomic changes in ALS mouse motor neurons and patients' skin fibroblasts. We first observed that SODG93A mice presymptomatic motor neurons display alterations in the coupling efficiency of oxidative phosphorylation, along with fragmentation of the mitochondrial network. The proteome of presymptomatic ALS mice motor neurons also revealed a peculiar metabolic signature with upregulation of most energy-transducing enzymes, including the fatty acid oxidation (FAO) and the ketogenic components HADHA and ACAT2, respectively. Accordingly, FAO inhibition altered cell viability specifically in ALS mice motor neurons, while uncoupling protein 2 (UCP2) inhibition recovered cellular ATP levels and mitochondrial network morphology. These findings suggest a novel hypothesis of ALS bioenergetics linking FAO and UCP2. Lastly, we provide a unique set of data comparing the molecular alterations found in human ALS patients' skin fibroblasts and SODG93A mouse motor neurons, revealing conserved changes in protein translation, folding and assembly, tRNA aminoacylation and cell adhesion processes.

SmartPilot® view-guided anaesthesia improves postoperative outcomes in hip fracture surgery: a randomized blinded controlled study.

BACKGROUND: Both under-dosage and over-dosage of general anaesthetics can harm frail patients. We hypothesised that computer-assisted anaesthesia using pharmacokinetic/pharmacodynamic models guided by SmartPilot® View (SPV) software could optimise depth of anaesthesia and improve outcomes in patients undergoing hip fracture surgery. METHODS: This prospective, randomized, single-centre, blinded trial included patients undergoing hip fracture surgery under general anaesthesia. In the intervention group, anaesthesia was guided using SPV with predefined targets. In the control group, anaesthesia was delivered by usual practice using the same agents (propofol, sufentanil and desflurane). The primary endpoint was the time spent in the "appropriate anaesthesia zone" defined as bispectral index (BIS) (blinded to the anaesthetist during surgery) of 45-60 and systolic arterial pressure of 80-140 mm Hg. Postoperative complications were recorded for one month in a blinded manner. RESULTS: Of 100 subjects randomised, 97 were analysed (n=47 in SPV and 50 in control group). Anaesthetic drug consumption was reduced in the SPV group (for propofol and desflurane). Intraoperative duration of low BIS (<45) was similar, but cumulative time of low systolic arterial pressure (<80 mm Hg) was significantly shorter in the SPV group (median (Q1-Q3); 3 (0-40) vs 5 (0-116) min, P=0.013). SPV subjects experienced fewer moderate or major postoperative complications at 30-days (8 (17)% vs 18 (36)%, P=0.035) and shorter length of hospitalisation (8 (2-20) vs 8 (2-60) days, P=0.017). CONCLUSIONS: SmartPilot® View-guided anaesthesia reduces intraoperative hypotension duration, occurrence of postoperative complications and length of stay in hip fracture surgery patients. CLINICAL TRIAL REGISTRATION: NCT 02556658.

Contribution of limb momentum to power transfer in athletic wheelchair pushing.

Pushing capacity is a key parameter in athletic racing wheelchair performance. This study estimated the potential contribution of upper limb momentum to pushing. The question is relevant since it may affect the training strategy adopted by an athlete. A muscle-free Lagrangian dynamic model of the upper limb segments was developed and theoretical predictions of power transfer to the wheelchair were computed during the push phase. Results show that limb momentum capacity for pushing can be in the order of 40J per push cycle at 10m/s, but it varies with the specific pushing range chosen by the athlete. Although use of momentum could certainly help an athlete improve performance, quantifying the actual contribution of limb momentum to pushing is not trivial. A preliminary experimental investigation on an ergometer, along with a simplified model of the upper limb, suggests that momentum is not the sole contributor to power transfer to a wheelchair. Muscles substantially contribute to pushing, even at high speeds. Moreover, an optimal pushing range is challenging to find since it most likely differs if an athlete chooses a limb momentum pushing strategy versus a muscular exertion pushing strategy, or both at the same time. The study emphasizes the importance of controlling pushing range, although one should optimize it while also taking the dynamics of the recovery period into account.

Seasonal gonadal development and age-related maturity patterns of introduced pumpkinseed (Lepomis gibbosus Linnaeus, 1758) in a heated thermal reservoir and an adjacent river reach.

Testis and ovarian maturation status, maturity profile and gonado-somatic index (GSI) were assessed in pumpkinseed (Lepomis gibbosus) collected from Mirgenbach, a cooling-water reservoir associated with a nuclear power plant, and from the River Moselle 7km downstream of the reservoir's thermal outflow. Histological investigation indicated that in both sexes, gonadal development of pumpkinseed in the heated reservoir was more advanced than in the cooler Moselle River throughout the breeding season. The histological maturity profile of reservoir males ranked by the advancement of sperm cells was highly correlated with its GSI (rs=0.73, P<0.001). GSI of females in the reservoir increased with the stage at maturity, but GSI was not significantly correlated with total length, age or growth rate of the individual. All sampled individuals of both sexes were mature at age 1 in the heated reservoir, whereas 48% of age 1 males and 57% of age 1 females were not mature in the river. GSI patterns suggest that males in the reservoir adopted one of two reproductive strategies (nesters or cuckolders), whereas no small males with large enough testes to be considered cuckolders were apparent in the river. The warm thermal regime of Mirgenbach Reservoir led to precocial maturity, early season reproduction, and the greater prevalence of apparent cuckolder males than would normally occur in this climatic zone.

A rare missense mutation in CHRNA4 associates with smoking behavior and its consequences.

Using Icelandic whole-genome sequence data and an imputation approach we searched for rare sequence variants in CHRNA4 and tested them for association with nicotine dependence. We show that carriers of a rare missense variant (allele frequency=0.24%) within CHRNA4, encoding an R336C substitution, have greater risk of nicotine addiction than non-carriers as assessed by the Fagerstrom Test for Nicotine Dependence (P=1.2 × 10(-4)). The variant also confers risk of several serious smoking-related diseases previously shown to be associated with the D398N substitution in CHRNA5. We observed odds ratios (ORs) of 1.7-2.3 for lung cancer (LC; P=4.0 × 10(-4)), chronic obstructive pulmonary disease (COPD; P=9.3 × 10(-4)), peripheral artery disease (PAD; P=0.090) and abdominal aortic aneurysms (AAAs; P=0.12), and the variant associates strongly with the early-onset forms of LC (OR=4.49, P=2.2 × 10(-4)), COPD (OR=3.22, P=2.9 × 10(-4)), PAD (OR=3.47, P=9.2 × 10(-3)) and AAA (OR=6.44, P=6.3 × 10(-3)). Joint analysis of the four smoking-related diseases reveals significant association (P=6.8 × 10(-5)), particularly for early-onset cases (P=2.1 × 10(-7)). Our results are in agreement with functional studies showing that the human α4ß2 isoform of the channel containing R336C has less sensitivity for its agonists than the wild-type form following nicotine incubation.

'It's something you have to put up with'--service users' experiences of in utero transfer: a qualitative study.

OBJECTIVE: The purpose of this study was to gain in-depth insight and enhance understanding of service users' experiences of the in utero transfer (IUT) process, in order to inform policy and improve the current service provision of maternal care. DESIGN: Qualitative descriptive study using semi-structured interviews. SETTING: Participant's home or hospital in the Midlands, UK. POPULATION: Fifteen women transferred in utero to a tertiary level maternity hospital; five male partners and two grandmothers. METHODS: Audio-recorded individual or paired semi-structured interviews transcribed verbatum and analysed thematically using nvivo 9. MAIN OUTCOME MEASURES: Facilitators and barriers of the IUT experience. RESULTS: Findings suggest that IUT is an emotional experience that financially disadvantages patients and their families. Male partners were perceived to be most negatively affected by the experience. The quality of the IUT experience was influenced by a range of factors, including the lack of proximity to home and the lack of information. Patients had little knowledge or awareness of IUT, and most felt unprepared for displacement. Despite this, there was resigned acceptance that IUT was a necessary rather than adverse experience. CONCLUSIONS: The experience of IUT for service users could be enhanced by ensuring that they are better informed about the process and the circumstances that necessitate displacement, that they are better informed about the hospital to which they are being transferred, and that they are transferred as close to home as possible. Efforts to minimise the emotional and socio-economic impact of IUT on women and their families also need to be considered.

Impact of the cestode Triaenophorus nodulosus on the exotic Lepomis gibbosus and the autochthonous Perca fluviatilis.

The effects of plerocercoids of the cestode Triaenophorus nodulosus infecting the livers of native Eurasian perch Perca fluviatilis and non-native pumpkinseed Lepomis gibbosus was investigated in 17 sites along the Moselle watershed. With a single exception, infected individuals were not observed in the main channel whether or not northern pike Esox lucius, a final host, was present. In ponds where the pike was present, the prevalence of T. nodulosus averaged 86% in Eurasian perch and 15% in pumpkinseed. The parasite was not present at all in ponds when pike were absent. Parasite load, hepatosomatic index (HSI), gonadosomatic index (GSI) and body condition index (CI) were compared between hosts in one site where parasite prevalence and fish abundance was highest. HSI in infected perch was significantly higher than in uninfected perch, whereas no differences in HSI were detected between infected and uninfected pumpkinseed. While perch were more frequently infected and had a greater average parasite load than pumpkinseed, there were no significant differences in either indicator between the two species. Furthermore, no significant differences in GSI or CI were observed between infected and uninfected fish in either species, by either gender or maturity stage. We hypothesize that pumpkinseed is more resistant to the parasite or less likely to feed upon infected copepods than perch.

Bifurcation study of a neural field competition model with an application to perceptual switching in motion integration.

Perceptual multistability is a phenomenon in which alternate interpretations of a fixed stimulus are perceived intermittently. Although correlates between activity in specific cortical areas and perception have been found, the complex patterns of activity and the underlying mechanisms that gate multistable perception are little understood. Here, we present a neural field competition model in which competing states are represented in a continuous feature space. Bifurcation analysis is used to describe the different types of complex spatio-temporal dynamics produced by the model in terms of several parameters and for different inputs. The dynamics of the model was then compared to human perception investigated psychophysically during long presentations of an ambiguous, multistable motion pattern known as the barberpole illusion. In order to do this, the model is operated in a parameter range where known physiological response properties are reproduced whilst also working close to bifurcation. The model accounts for characteristic behaviour from the psychophysical experiments in terms of the type of switching observed and changes in the rate of switching with respect to contrast. In this way, the modelling study sheds light on the underlying mechanisms that drive perceptual switching in different contrast regimes. The general approach presented is applicable to a broad range of perceptual competition problems in which spatial interactions play a role.

Host switch and infestation by Ligula intestinalis L. in a silver bream (Blicca bjoerkna L.) population.

Sampling of the fish community was carried out for 20 years in the Mirgenbach reservoir, in North-Eastern France. The prevalence and the mean intensity of Ligula intestinalis (Cestoda) were analysed in roach (Rutilus rutilus) and silver bream (Blicca bjoerkna) populations, the main two infected species. The aim of this study was to investigate the host switch from roach to silver bream and the consequences of L. intestinalis infestation in silver bream, which is an unusual host for this parasite as Ligula parasitism in silver bream appears to be rare. We analysed in detail the relationships between parasitism index (PI), gonadosomatic index (GSI), perivisceral fat abundance (PFA) and condition index (CI) in the silver bream population. In 1998, prevalence of L. intestinalis highlighted a clear host switch from roach to silver bream. In the silver bream population, young fish were the most severely infected and the impact of plerocercoids appeared to be different depending on the host sex. In male silver bream, plerocercoids drew energy from fat reserves even if GSI was also slightly impacted. On the contrary, in females energy was diverted from gonad maturation rather than from perivisceral fat reserves. No significant difference was observed in terms of CI in either sex.

Avaliação econômica da utilização de diferentes níveis de polpa cítrica com ou sem adição de complexo enzimático nas dietas de suínos / Economic evaluation of the use of different levels of citrus pulp with or without the addition of enzyme complex in the diets of pigs

Avaliou-se economicamente o efeito da inclusãode 0, 5, 10 e 15 por cento de polpa cítrica (PC), com ou sem adição do complexo enzimático, sobre o desempenho de 72 suínos, dos 25,71±7,51 aos 98,81±10,64kg de peso. Com este peso final, os animais foram abatidos, e dos valores (R$) da carcaça, incluindo os índices de bonificação, foram descontados o valor de compra dos animais e os custos com alimentação, de acordo com cada tratamento. Para os custos com alimentação, foi observado aumento linear (P=0,0190), enquanto para as receitas bruta (P=0,0328) e líquida (P=0,0013) parciais foram encontradas reduções lineares em função das porcentagens de PC com ou sem a adição do complexo enzimático. Considerando-se a evolução dos preços do milho, farelo de soja e do suíno durante o ano de 2008, foram determinados 12 cenários diferentes para a receita líquida parcial e, em todos eles, foi observada redução linear em função da inclusão da PC, com ou sem adição do complexo enzimático. Conclui-se que a utilização de PC, com ou sem adição do complexo enzimático, não reduziu os custos com alimentação, não sendo economicamente viável sua inclusão nas rações de suínos em crescimento e terminação.

An economic evaluation was done in order to evaluate the effect of the inclusion of 0, 5, 10 and 15 percent of citrus pulp (PC), with or without the addition of the enzyme complex, on the performance of 72 pigs from 25.71±7.51 to 98.81±10.64kg of body weight. The animals were slaughtered when they reached 98.81kg. The purchase value of the animals and feed costs (R$) were discounted from the carcass value, including subsidy rates (R$). A linear increase (P= 0.0190) was observed, while linear reductions were observed for the gross receipts (P=0.0328) and net (P = 0.0013) partials, due to the inclusion of PC in the diet with or without the enzyme complex. Considering the evolution of corn, soybean meal and pig prices during 2008, there were some 12 different scenarios for partial and net income determined and in all of them, linear reductions were observed due to the inclusion of PC in the diet with or without the enzyme complex. The use of PC with or without the addition of the enzyme complex was unable to reduce the costs of feed.

A library of analog operators based on the hodgkin-huxley formalism for the design of tunable, real-time, silicon neurons.

In this paper, we present a library of analog operators used for the analog real-time computation of the Hodgkin-Huxley formalism. These operators make it possible to design a silicon (Si) neuron that is dynamically tunable, and that reproduces different kinds of neurons. We used an original method in neuromorphic engineering to characterize this Si neuron. In electrophysiology, this method is well known as the "voltage-clamp" technique. We also compare the features of an application-specific integrated circuit built with this library with results obtained from software simulations. We then present the complex behavior of neural membrane voltages and the potential applications of this Si neuron.

Infecção experimental por Salmonella enterica subespécie enterica sorotipo Panama e tentativa de transmissão nasonasal em leitões desmamados / Experimental infection by Salmonella enterica ssp. enterica serovar Panama and tentative of nose-to-nose transmission in weaned pigs

O objetivo deste experimento foi produzir uma infecção experimental de Salmonella enterica subespécie. enterica sorotipo Panama e verificar a importância da via nasonasal na transmissão entre leitões desmamados. Foram utilizados seis leitões recém-desmamados, adquiridos de granja livre de Salmonella spp. Utilizaram-se baias isoladoras, que proporcionavam o contato nasonasal e eliminavam a possibilidade de outras vias de transmissão e de contaminação externa. Três grupos foram formados: controle, sentinela e infectado. Não foram encontradas amostras positivas para Salmonella spp. em leitões do grupo-controle e sentinelas, e nos animais infectados foi isolada Salmonella Panama em suabes retais e tecidos necropsiados. Os resultados revelaram não haver a transmissão pela via nasonasal entre leitões desmamados, pois, em nenhum momento, o agente foi isolado dos animais sentinelas.

Experimental infection of Salmonella enterica ssp. enterica serovars Panama was proceeded to establish the importance of nose-to-nose contact in the transmission among weaned pigs. Six recently-weaned pigs were acquired from a farm previously selected, free from Salmonella spp. Isolation stalls allowing nose-to-nose contact and eliminating other transmission routes as well outside contamination were used. Three groups were formed: control, sentinel, and infected. Piglets of control and sentinel groups were not positive for Salmonella spp., however, Salmonella Panama was isolated in infected animals in rectal swabs and necropsied tissues. It was concluded that there was not transmission by nose-to-nose contact among weaned pigs, since Samonella Panama was not isolated in the sentinel group at any moment.

Carcass characteristics and meat quality of heavy swine fed different citrus pulp levels / Características de carcaça e qualidade da carne de suínos com elevado peso de abate, alimentados com dietas contendo diferentes níveis de polpa cítrica

An assay with 36 swine initially weighting 83.7±5.1kg body weight (BW) was carried out to evaluate the effects of the use of different dietary citrus pulp levels, 0, 10 percent, 20 percent, and 30 percent, upon digestive organs weights, carcass characteristics, and meat quality of animals subjected to qualitative feed restriction program, and slaughtered at 130kg BW. Linear response (P<0.05) on the weight of stomach, colon, and liver were observed. Negative linear responses (P<0.05) on final BW and carcass yield relative to citrus pulp addition to the diet were observed. Although a negative linear effect (P<0.05) of increasing dietary levels of citrus pulp had been observed on ham weight, yield of this by product was not affected (P>0.05). Higher levels of citrus pulp neither decreased backfat thickness nor increased amount of lean meat, indicative that qualitative feed restriction was not efficient. Positive linear effect (P<0.05) on pH measured 24 hours after slaughter and negative linear effect (P<0.05) on color characteristics as function of citrus pulp dietary levels were verified. Citrus pulp addition in qualitative feed restriction program may not be effective. As no deleterious effects upon meat qualities were observed, citrus pulp can be used as an alternative feedstuff for finishing swine.

Foi realizado um ensaio utilizando 36 suínos machos castrados, com peso inicial de 83,7±5,1kg, para avaliar o efeito da inclusão de polpa cítrica, 0, 10, 20 e 30 por cento, em um programa de restrição alimentar qualitativa para suínos abatidos aos 130kg de peso, sobre o peso dos órgãos do sistema digestório e sobre características da carcaça e da qualidade da carne. A inclusão de polpa cítrica proporcionou aumento linear (P<0,05) nos pesos do estômago, cólon e fígado, e efeito quadrático (P<0,05) no peso do ceco. Foi observada redução linear (P<0,05) no peso, no rendimento da carcaça e no peso do pernil, porém não houve efeito (P>0,05) sobre o rendimento do pernil. Maior inclusão de polpa cítrica não foi suficiente para reduzir a espessura do toucinho e aumentar a quantidade de carne magra na carcaça, mostrando que a restrição alimentar qualitativa não foi eficiente. Foi observado aumento linear (P<0,05) do pH da carcaça resfriada e linear negativo (P<0,05) sobre as variáveis indicativas de cor da carne em função da inclusão da polpa cítrica nas dietas. A adição de polpa cítrica em programas de restrição alimentar qualitativa não foi eficiente. Por não promover nenhum efeito deletério sobre as características da carne, a polpa cítrica pode ser utilizada como ingrediente alternativo para suínos em terminação.

[A 3T fMRI study of cortical projection of visual scotomas: preliminary results]. / Etude en IRM fonctionnelle 3T de la projection corticale de scotomes rétiniens: résultats préliminaires.

AIM: We used functional magnetic resonance imaging (fMRI) to precisely measure both the localization and size of the cortical projections of artificial scotomas in healthy subjects as well as the size of a reversible retinal scotoma in a patient with central serous chorioretinopathy (CSCR). METHODS: Using a 3T MRI scanner, anatomical and functional data were acquired on two healthy subjects and a patient with CSCR. Retinotopic maps were first reconstructed using phase mapping techniques. Next, a block paradigm consisting of a grey background alternating with a full-field, flickering checkerboard was used to stimulate the complete central (19.5 degrees) visual field. A condition with artificial peri-foveal scotomas of different sizes and eccentricities was interleaved in healthy subjects. Differential maps were computed to obtain the cortical representation (size and location) of artificial scotomas. Full-field functional data were also acquired in the CSRC patient, at the acute stage and after recovery. RESULTS: Cortical projections of each scotoma were identified using differential maps and carefully characterized with quantitative analysis: the measured cortical positions of the inactivated cortical zones were compared with the known radius and eccentricity values in the scotomas in the visual field. We also compared the size of the inactivated cortical zones to the known size of scotomas. However, we found a consistent relationship between the size of the scotomas and their cortical projections, albeit with the absolute size smaller than expected from known cortical magnification factors. The cortical deactivation zone was also observed in the CRSC patient, which disappeared at recovery stage. CONCLUSIONS: Cortical retinotopic mapping can be performed successfully for both artificial and retinal scotomas. This study can serve as a basis for the future investigation of cortical plasticity in the visual cortex.

Causes of death amongst French patients with amyotrophic lateral sclerosis: a prospective study.

BACKGROUND AND PURPOSE: To prospectively investigate causes of death and the circumstances surrounding death in 302 patients with amyotrophic lateral sclerosis (ALS). The functional status of patients immediately before death was also determined. METHODS: Information was obtained from neurologists at ALS centres, patients' files, and, when deaths occurred outside a medical facility, attending physicians. RESULTS: Most patients (63%) died in a medical facility. The most frequently reported cause of death was respiratory failure (77%), including terminal respiratory insufficiency (58%), pneumonia (14%), asphyxia due to a foreign body (3%) and pulmonary embolism (2%). Ten per cent of patients died from other causes: post-surgical or traumatic conditions (5%), cardiac causes (3.4%), suicide (1.3%) and sudden death of unknown origin (0.7%). The cause of death could not be determined in 13% of cases (6% inside a medical facility and 25% outside). At the time of death, only 55% of patients were receiving riluzole, 33% were undergoing non-invasive ventilation, 3% had a tracheotomy and 37% a gastrostomy. CONCLUSION: The information provided by this study helps to improve our understanding of the natural history of the disease and may help optimize the quality of care we can offer patients at the end of life.

CDKN2A mutations and melanoma risk in the Icelandic population.

BACKGROUND: Germline CDKN2A mutations have been observed in 20-40% of high risk, melanoma prone families; however, little is known about their prevalence in population based series of melanoma cases and controls. METHODS: We resequenced the CDKN2A gene, including the p14ARF variant and promoter regions, in approximately 703 registry ascertained melanoma cases and 691 population based controls from Iceland, a country in which the incidence of melanoma has increased rapidly. RESULTS: We identified a novel germline variant, G89D, that was strongly associated with increased melanoma risk and appeared to be an Icelandic founder mutation. The G89D variant was present in about 2% of Icelandic invasive cutaneous malignant melanoma cases. Relatives of affected G89D carriers were at significantly increased risk of melanoma, head and neck cancers, and pancreatic carcinoma compared to relatives of other melanoma patients. Nineteen other germline variants were identified, but none conferred an unequivocal risk of melanoma. CONCLUSIONS: This population based study of Icelandic melanoma cases and controls showed a frequency of disease related CDKN2A mutant alleles ranging from 0.7% to 1.0%, thus expanding our knowledge about the frequency of CDKN2A mutations in different populations. In contrast to North America and Australia where a broad spectrum of mutations was observed at a similar frequency, in Iceland, functional CDKN2A mutations consist of only one or two different variants. Additional genetic and/or environmental factors are likely critical for explaining the high incidence rates for melanoma in Iceland. This study adds to the geographic regions for which population based estimates of CDKN2A mutation frequencies are available.