LIFETIME AMBIENT ULTRAVIOLET RADIATION EXPOSURE AND INCIDENCE OF AGE-RELATED MACULAR DEGENERATION.

PURPOSE: To investigate the link between lifelong exposure to ultraviolet radiation (UVR) and the development of age-related macular degeneration (AMD). METHODS: The Alienor study is a prospective population-based cohort involving 963 residents of Bordeaux, France, older than 73 years. A subset of 614 participants for advanced AMD and 422 participants for early AMD were included in the analysis. The participants' residential history combined with UVR estimates from the EuroSun satellite were used to estimate the amount of ambient UVR they have been exposed to over their lifetime. Age-related macular degeneration was classified from retinal fundus photographs and spectral domain optical coherence tomography at 2 to 3 years intervals over the 2006 to 2017 period. Associations between cumulative exposure to ultraviolet A, ultraviolet B, and total (total UV) and the incidence of early and advanced AMD were estimated using multivariate Cox models. RESULTS: Intermediate quartiles of total UV, ultraviolet A, and ultraviolet B exposures were associated with a higher risk for incident early AMD (Hazard Ratio [HR] =2.01 [95% confidence interval [CI] = 1.27-3.13], HR = 2.20 [95% CI = 1.38-3.50], HR = 1.79 [95% CI = 1.13-2.80], respectively) as compared with the lower quartile. However, this risk did not further increase in the highest quartiles of exposure. None of the three types of UVR exposure was significantly associated with incident advanced AMD. CONCLUSION: Despite an increased risk with intermediate compared with low UVR exposure, our study cannot confirm a dose-response relationship of UVR exposure with early AMD onset.

Health disturbances and exposure to radiofrequency electromagnetic fields from mobile-phone base stations in French urban areas.

The effects of radiofrequency exposure on the health of people living near mobile-phone base stations (MPBSs) have been the subject of several studies since the mid-2000s, with contradictory results. We aimed to investigate the association between measured exposure to radiofrequency electromagnetic fields (RF-EMF) from MPBSs and the presence of self-reported non-specific and insomnia-like symptoms. A cross-sectional survey conducted between 2015 and 2017 in five large cities in France involved 354 people living in buildings located at a distance of 250 m or less from an MPBS and in the main transmit beam of the antennas. Information on environmental concerns, anxiety, and non-specific and insomnia-like symptoms was collected with a questionnaire administrated by telephone. A complete broadband field-meter measurement [100 kHz - 6 GHz] was then made at five points of each dwelling, followed by a spectral analysis at the point of highest exposure, detailing the contribution of each service, including MPBS. The median exposure from MPBS was 0.27 V/m (0.44 V/m for global field), ranging from 0.03 V/m to 3.58 V/m, MPBSs being the main source of exposure for 64% of the dwellings. In this study population, the measured exposure from MPBSs was not associated with self-reported non-specific or insomnia-like symptoms. However, for insomnia-like symptoms, a significant interaction was found between RF-EMF exposure from MPBSs and environmental concerns. These findings do not support the hypothesis of an effect of RF-EMF from MPBSs on non-specific or insomnia-like symptoms in the overall population. Studies are needed to further investigate the positive association observed between exposure from MPBSs and insomnia-like symptoms among people reporting environmental concerns.

Radiofrequency exposure of people living near mobile-phone base stations in France.

In response to the demand from a growing number of people concerned about the possible impact of RF-EMF on health, the French National Frequency Agency (ANFR) has published a standardized protocol for in-situ measurements of radiofrequency electromagnetic fields (RF-EMF). This protocol was based on the search for the point of highest field strength and the use of spot measurement. In the framework of an epidemiological study, such spot measurements were implemented in the homes of 354 participants located in urban areas within 250 m of a mobile-phone base station (MPBS) and in the main beam direction of the antenna. Among the participants, more than half accepted to be enrolled in a longer-term study, among whom 152 were equipped with a personal exposure meter (PEM) for 48 h and 40 for seven continuous days. Both spot and PEM measurements quantified downlink field strengths, i.e. FM, TV3-4-5, TETRA I-II-III, 2 GHz-5GHz Wi-Fi, WiMax, GSM900, GSM1800, UMTS900, UMTS 2100, LTE800, LTE1800, and LTE2600. Spot measurements showed a mean/median field strength of 0.58/0.44 V/m for total RF-EMF and 0.43/0.27 V/m from the MPBS. RF-EMF from the MPBS was the dominant source of exposure in 64% of households. Exposure to RF-EMF was influenced by the position of the windows with respect to the MPBS, in particular line-of-site visibility, the distance of the antenna and the floor of the apartment. The PEM surveys showed the measured exposure to be higher during outings than at home and during the day than at night, but there was no difference between the weekends and working days. There was a strong correlation between exposure quantified by both spot and PEM measurements, although spot measures were approximately three times higher than those by PEMs. This study is the first to assess exposure to RF-EMF of people living near a MPBS in urban areas in France. These preliminary results suggest the value of using spot measurements to estimate the impact of the evolution of the mobile-phone network and technology on the exposure of populations to RF-EMF. The low levels of RF-RMF expressed as mean values do not necessarily rule out possible health effects of this exposure.

Invited Commentary: Indoor Tanning-A Melanoma Accelerator?

In this issue of the Journal, Ghiasvand et al. (Am J Epidemiol. 2017;185(3):147-156) present results from a longitudinal study of the association between indoor tanning and melanoma in a large cohort of Norwegian women. These new data further support previous findings on the damaging effects of tanning bed exposure on women, particularly young women. The authors present compelling evidence that early exposure to tanning beds advances the date of diagnosis of melanoma by at least 2 years. With a strong design and a large cohort followed for a mean of 13.7 years, this study lends additional support to previous evidence of the negative effects of tanning beds and provides further justification for stronger policy initiatives designed to reduce tanning bed use among young women.

Residential exposure to ultraviolet light and risk of precursor B-cell acute lymphoblastic leukemia: assessing the role of individual risk factors, the ESCALE and ESTELLE studies.

BACKGROUND: In a previous nationwide ecological study based on 20 years of registration and 7,443 cases of acute lymphoblastic leukemia (ALL), we reported a positive association between residential solar ultraviolet (UV) light at diagnosis and childhood precursor B-cell acute lymphoblastic leukemia (PBC-ALL). OBJECTIVE: The present study investigated the influence of suspected individual risk factors for ALL on the association between UV and PBC-ALL, and evaluated this association at the residence at birth. METHODS: Individual data collected by interviews in the ESCALE (2003-2004) and ESTELLE (2010-2011) nationwide case-control studies, which included 1,511 cases of leukemia aged less than 15 years and 3,102 population controls, were analyzed. Municipalities of residences at birth and at diagnosis/interview were extracted and assigned UV radiation exposure from the EUROSUN database. The potential confounders or effect modifiers considered were strongly suspected risk factors for ALL that were available in the ESCALE and ESTELLE studies. RESULTS: UV exposure at diagnosis was associated with PBC-ALL (OR = 1.27 [1.08-1.48]) for UV > 105.5 J/cm2 compared to UV ≤ 105.5 J/cm2. Considering exposure to UV at birth rather than at diagnosis/inclusion yielded almost identical results as both variables were strongly correlated. Taking into account the suspected ALL risk factors did not affect this association in the pooled study. CONCLUSION: Our findings suggest that our previous observation of an ecological association between residential UV radiation exposure at diagnosis and PBC-ALL was not confounded or modified by individual risk factors, and that the critical exposure time window may be prenatal.

UV Driven Tanning Salons: Danger on Main Street.

Appearing in the early 1980s, at a time when UVA was considered as relatively safe, the tanning industry has substantially developed in occidental countries, especially in Northern European countries. In Europe, the erythemally-weighted irradiance of a modern sunbed should not exceed 0.3 W/m2, equivalent to an UV index of 12, i.e. to a tropical midday sun, but increased in recent years, the UV spectrum emitted by sunbeds had evolved towards higher UVA irradiance and solariums UV had become even less similar to natural sun.

Residential exposure to solar ultraviolet radiation and incidence of childhood hematological malignancies in France.

PURPOSE: Few studies have investigated the relationship between solar ultraviolet radiation (UV) and childhood hematological malignancies (CHM). This study addresses the associations between residential UV exposure at diagnosis and the incidence of types and subtypes of CHM, by age and gender, in France, over a long period, on the fine scale of the 36,326 Communes that constitute mainland France. METHODS: The 9,082 cases of acute leukemia and 3,563 cases of lymphoma diagnosed before the age of 15 years from 1990 to 2009 were provided by the French National Registry of Childhood Hematological Malignancies. The incidence of CHM was calculated by Commune, year, age and gender and expressed as the standardized incidence ratio (SIR). UV data from 1988 to 2007 were extracted from the EUROSUN database. RESULTS: The annual daily average UV exposure of the children ranged from 85.5 to 137.8 J/cm(2). For each additional 25 J/cm(2), there was a significant increase in precursor B-cell acute lymphoblastic leukemia (PBC-ALL) in children aged less than 5 years (SIR 1.18; 95% CI 1.10-1.27). Further analysis of PBC-ALL in the young children suggested a better fit of models with a threshold, with the risk increasing above 100 J/cm(2), for which the SIR was 1.24 (95% CI 1.14-1.36) for a 25 J/cm(2) increase. The results remained stable in analyses stratifying by deprivation index or degree of urbanization of the Communes. CONCLUSION: The study suggests that higher residential UV exposure may be positively associated with a higher incidence of PBC-ALL in early childhood.

Effect of Lactobacillus rhamnosus CGMCC1.3724 supplementation on weight loss and maintenance in obese men and women.

The present study investigated the impact of a Lactobacillus rhamnosus CGMCC1.3724 (LPR) supplementation on weight loss and maintenance in obese men and women over 24 weeks. In a double-blind, placebo-controlled, randomised trial, each subject consumed two capsules per d of either a placebo or a LPR formulation (1.6 × 10(8) colony-forming units of LPR/capsule with oligofructose and inulin). Each group was submitted to moderate energy restriction for the first 12 weeks followed by 12 weeks of weight maintenance. Body weight and composition were measured at baseline, at week 12 and at week 24. The intention-to-treat analysis showed that after the first 12 weeks and after 24 weeks, mean weight loss was not significantly different between the LPR and placebo groups when all the subjects were considered. However, a significant treatment × sex interaction was observed. The mean weight loss in women in the LPR group was significantly higher than that in women in the placebo group (P = 0.02) after the first 12 weeks, whereas it was similar in men in the two groups (P= 0.53). Women in the LPR group continued to lose body weight and fat mass during the weight-maintenance period, whereas opposite changes were observed in the placebo group. Changes in body weight and fat mass during the weight-maintenance period were similar in men in both the groups. LPR-induced weight loss in women was associated not only with significant reductions in fat mass and circulating leptin concentrations but also with the relative abundance of bacteria of the Lachnospiraceae family in faeces. The present study shows that the Lactobacillus rhamnosus CGMCC1.3724 formulation helps obese women to achieve sustainable weight loss.

Modulation of physical activity to optimize pain sensation following an intra-articular corticosteroid injection in patients with knee osteoarthritis.

BACKGROUND: Intra-articular corticosteroid injection is often used to relieve pain caused by knee osteoarthritis. This study aims to assess the impact after an intra-articular corticosteroid injection treatment on objective and subjective measurement of physical function in knee osteoarthritis patients. METHODS: Fourteen patients with unilateral knee osteoarthritis participated in this open-label uncontrolled trial. The intra-articular corticosteroid injection was given at the end of the second week. Physical activity was objectively measured by an accelerometer worn by the participants for eight weeks. Symptoms, quality of life and spatiotemporal parameters of gait were assessed every two weeks. RESULTS: From the injection until six weeks later, pain and stiffness were reduced by approximately 60%. Patients' daily physical activity time was significantly improved after injection: participation in light and moderate physical activities increased during four and two weeks, respectively. CONCLUSIONS: The beneficial effects after the intra-articular corticosteroid injection are visible in the duration and intensity of the knee osteoarthritis patients' daily physical activity. However, these effects declined gradually two weeks after injection. Modulating the intensity and duration of physical activity would allow patients to optimize pain sensation over a longer period following an intra-articular corticosteroid injection. Trial Registration. This trial was registered with ClinicalTrials: NCT02049879.

Maximal cardiorespiratory fitness testing in individuals with chronic stroke with cognitive impairment: practice test effects and test-retest reliability.

OBJECTIVES: To evaluate, for individuals with chronic stroke with cognitive impairment, (1) the effects of a practice test on peak cardiorespiratory fitness test results; (2) cardiorespiratory fitness test-retest reliability; and (3) the relationship between individual practice test effects and cognitive impairment. DESIGN: Cross-sectional. SETTING: Rehabilitation center. PARTICIPANTS: A convenience sample of 21 persons (men [n=12] and women [n=9]; age range, 48-81y; 44.9±36.2mo poststroke) with cognitive impairments who had sufficient lower limb function to perform the test. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURE: Peak oxygen consumption (Vo(2)peak, ml·kg(-1)·min(-1)). RESULTS: Test-retest reliability of Vo(2)peak was excellent (intraclass correlation coefficient model 2,1 [ICC2,1]=.94; 95% confidence interval [CI], .86-.98). A paired t test showed that there was no significant difference for the group for Vo(2)peak obtained from 2 symptom-limited cardiorespiratory fitness tests performed 1 week apart on a semirecumbent cycle ergometer (test 2-test 1 difference, -.32ml·kg(-1)·min(-1); 95% CI, -.69 to 1.33ml·kg(-1)·min(-1); P=.512). Individual test-retest differences in Vo(2)peak were, however, positively related to general cognitive function as measured by the Mini-Mental State Examination (ρ=.485; P<.026). CONCLUSIONS: Vo(2)peak can be reliably measured in this group without a practice test. General cognitive function, however, may influence the effect of a practice test in that those with lower general cognitive function appear to respond differently to a practice test than those with higher cognitive function.

Tanning salons and skin cancer.

Indoor tanning has substantially grown in USA and Europe, more especially in the sun-deprived Northern countries, but also in more sunny countries such as Queensland, Australia. Several studies have specifically addressed the prevalence of sunbed use by children and adolescents in Northern Europe and in the USA, and showed that up to 40-50% of teenagers 15-18 years old had ever used indoor tanning, the highest figures being observed among girls in Scandinavia and Minnesota. Indoor tanning among adults is mostly prevalent in age classes younger than 45. Epidemiological studies have shown that exposure to sunbeds increases the risk of both melanoma and non-melanoma skin cancers: a meta-analysis of 19 studies published before 2006 showed that ever-use of sunbeds was positively associated with melanoma (summary relative risk, 1.15; 95% CI, 1.00-1.31), and first exposure before 35 years of age significantly increased melanoma risk (7 studies, RR = 1.75; 95% CI, 1.35-2.26). Further epidemiological data documented the links between artificial UV tanning and melanoma: two large case-control studies in Minnesota and Australia yielded higher melanoma risks for ever use of sunbeds: 1.74 (95%CI, 1.42-2.14) and 1.41 (95%CI, 1.01-1.96) respectively, risk increasing with greater use and earlier age at first use. The most compelling evidence derives from a large cohort of Norwegian and Swedish women which showed that melanoma risk increased with accumulating exposure (RR for solarium use ≥1 time per month in two or three decades, 10-39 years, 2.37 (95%CI, 1.37-4.08)). In addition, the analysis of a melanoma epidemic observed in Iceland between 1995 and 2002, on the trunk of women younger than 50, pointed out the possible role of the explosion of exposure to sunbeds in this country after 1985. Exposure to artificial ultraviolet is a risk factor for melanoma. Risk appears modest in the general population, but concentrates in the population that started sunbed use before the age of 35; the risk attributable to sunbed use in melanoma patients younger than 30 may be as high as 43 to 76%. Of particular concern is the use of sunbeds by adolescents. Use of sunbeds should be strongly discouraged, and banned under the age of 18.

Analysis of the peripheral T-cell repertoire in kidney transplant patients.

The long-term stability of renal grafts depends on the absence of chronic rejection. As T cells play a key role in rejection processes, analyzing the T-cell repertoire may be useful for understanding graft function outcomes. We have therefore investigated the power of a new statistical tool, used to analyze the peripheral blood TCR repertoire, for determining immunological differences in a group of 229 stable renal transplant patients undergoing immunosuppression. Despite selecting the patients according to stringent criteria, the patients displayed heterogeneous T-cell repertoire usage, ranging from unbiased to highly selected TCR repertoires; a skewed TCR repertoire correlating with an increase in the CD8(+) /CD4(+) T-cell ratio. T-cell repertoire patterns were compared in patients with clinically opposing outcomes i.e. stable drug-free operationally tolerant recipients and patients with the "suspicious" form of humoral chronic rejection and were found significantly different, from polyclonal to highly selected TCR repertoires, respectively. Moreover, a selected TCR repertoire was found to positively correlate with the Banff score grade. Collectively, these data suggest that TCR repertoire categorization might be included in the calculation of a composite score for the follow-up of patients after kidney transplantation.

Epidemiological evidence that UVA radiation is involved in the genesis of cutaneous melanoma.

PURPOSE OF REVIEW: Epidemiological data have contributed to the classification in 2009 of the full ultraviolet (UV) radiation spectrum as carcinogenic to humans. We reviewed the epidemiological evidence that UVA could be involved in the genesis of cutaneous melanoma. RECENT FINDINGS: Use of artificial UV tanning devices (sunbeds) consists mainly of repeated exposure to high UVA doses. Epidemiological studies published over the last years confirmed the association between sunbed use and melanoma. Sunbed use is the most probable cause of an epidemic of melanoma that took place in Iceland from 1990 to 2006. The four-fold increase in melanoma incidence was not followed by an increase in melanoma mortality. Sunscreens were primarily devised for the prevention of sunburn, and UVB is the wavelength causing most sunburns. All observational studies and randomized trials show that sunscreen use may extend sun exposure intended for getting a tan, while it does not necessarily decrease sunburn occurrence. Sunscreen use for tan acquisition would thus lead to similar exposure to UVB and greater exposure to UVA, which could explain the slightly higher melanoma risk often found among sunscreen users. SUMMARY: UVA could be involved in the occurrence of nonlife-threatening melanoma. The increasing use of sunbeds and of sunscreens may partly explain why melanoma incidence increases in most light-skinned populations without concomitant increase in mortality.

Erythemal and vitamin D weighted solar UV dose-rates and doses estimated from measurements in mainland France and on Réunion Island.

Solar UV radiation causes beneficial and detrimental changes in human health. International and national Health agencies recommend avoiding sun exposure when the solar rays are strongest (typically 2 h before and after solar noon). In this study we detail and refine such recommendations. We estimated biologically-effective radiation (inductive of erythema and pre-vitamin D) using spectral solar UV radiation measurements on a horizontal plane at three French sites equipped with spectroradiometers: Villeneuve d'Ascq (VDA) (North of France); Observatoire de Haute-Provence (OHP) (French Southern Alps); and Saint-Denis de La Réunion (SDR) on Réunion Island, in the Indian Ocean. These sites are very different: VDA is a semi-urban site in a flat region, OHP a rural mountainous site and SDR a coastal urban site on a small mountainous island. Biologically active radiation was analyzed by studying erythema induction and measuring pre-vitamin D synthesis. Dose-rates, doses and times for sunburn induction and vitamin D production were derived. Regarding the level of vitamin D dose considered here (1000 IU), we found that at mainland sites time required for vitamin D synthesis was relatively long, even around solar noon, in winter months this could be 2-3 h for phototype II individuals exposing their face and hands. In the tropics vitamin D could always be synthesized in a reasonable time (e.g. 20 min in winter). By contrast, in summer, the required duration times (exposing face, hands, arms and legs) are very short, approximately 2-4 min on the mainland and 1 min in the tropics for phototype II individuals. In all skin phototypes the duration of sun exposure required to induce erythema was generally longer than that to produce vitamin D. These quantitative results, obtained using an instrument measuring on a horizontal plane and with an unobstructed view, do not represent realistic values for human exposure. To account for realistic human body exposure, received doses and times of exposure were adjusted. Our study shows that, mostly in summer, the time periods where limited solar exposure is recommended should be extended, especially at low latitude locations.

A melanoma epidemic in Iceland: possible influence of sunbed use.

Since 1980, sunbed use and travel abroad have dramatically increased in Iceland (64°-66°N). The authors assessed temporal trends in melanoma incidence by body site in Iceland in relation to sunbed use and travel abroad. Using joinpoint analysis, they calculated estimated annual percent changes (EAPCs) and identified the years during which statistically significant changes in EAPC occurred. Between 1954 and 2006, the largest increase in incidence in men was observed on the trunk (EAPC = 4.6%, 95% confidence interval: 3.2, 6.0). In women, the slow increase in trunk melanoma incidence before 1995 was followed by a significantly sharper increase in incidence, mainly among women aged less than 50 years, resembling an epidemic incidence curve (1995-2002: EAPC = 20.4%, 95% confidence interval: 9.3, 32.8). In 2002, the melanoma incidence on the trunk was higher than the incidence on the lower limbs for women. Sunbed use in Iceland expanded rapidly after 1985, mainly among young women, and in 2000, it was approximately 2 and 3 times the levels recorded in Sweden and in the United Kingdom, respectively. Travels abroad were more prevalent among older Icelanders. The high prevalence of sunbed use probably contributed to the sharp increase in the incidence of melanoma in Iceland.

Ultraviolet radiation and cutaneous melanoma: a historical perspective.

In this article, we summarize the research that eventually led to the classification of the full ultraviolet (UV) radiation spectrum as carcinogenic to humans. We recall the pioneering works that led to the formulation of novel hypotheses on the reasons underlying the increasing burden of melanoma in light-skinned populations. It took long before having compelling evidence on the association between UV and melanoma, in particular, the importance of UV exposure during childhood for both the occurrence of melanoma and death. The role of UVA was established only after 2005. If molecular lesions caused by UV radiation are better known, the precise mechanism by which UV exposure drives melanoma occurrence and progression still needs to be elucidated. More research on the UV-melanoma relationships has led to more evidence-based sun-protection recommendations, especially for children, and to effective control of the artificial UV tanning fashion. Since around 1985-1995, the mortality because of melanoma has started to decrease in younger age groups in most light-skinned populations. If sun protection among children remain on top of public health agendas, there is a fairly great chance that melanoma mortality will stabilize and steadily decrease in all light-skinned populations. The introduction of effective therapies against metastatic disease will improve this reversal in mortality trends.

Calcium plus vitamin D supplementation and fat mass loss in female very low-calcium consumers: potential link with a calcium-specific appetite control.

This randomized, double-blind, placebo-controlled study was conducted to compare the effect of a 15-week weight-reducing programme ( -2900 kJ/d) coupled with a calcium plus vitamin D (calcium+D) supplementation (600 mg elemental calcium and 5 microg vitamin D, consumed twice a day) or with a placebo, on body fat and on spontaneous energy/macronutrient intake. Sixty-three overweight or obese women (mean age 43 years, mean BMI 32 kg/m2) reporting a daily calcium intake < 800 mg participated in present study. Anthropometric variables, resting energy expenditure and spontaneous energy intake were measured before and after the 15-week programme. The calcium+D supplementation induced no statistically significant increase in fat mass loss in response to the programme. However, when analyses were limited to very low-calcium consumers only (initial calcium intake < or =600 mg/d, n 7 for calcium+D, n 6 for placebo), a significant decrease in body weight and fat mass (P < 0.01) and in spontaneous dietary lipid intake (P < 0.05) was observed in the calcium+D but not in the placebo group. In very low-calcium consumers, change in fat mass was positively correlated with change in lipid intake. During the weight-reducing programme, a calcium+D supplementation was necessary in female overweight/obese very low-calcium consumers to reach significant fat mass loss that seemed to be partly explained by a decrease in lipid intake. We propose that this change in lipid intake could be influenced by a calcium-specific appetite control.

The contribution of large genomic deletions at the CDKN2A locus to the burden of familial melanoma.

Mutations in two genes encoding cell cycle regulatory proteins have been shown to cause familial cutaneous malignant melanoma (CMM). About 20% of melanoma-prone families bear a point mutation in the CDKN2A locus at 9p21, which encodes two unrelated proteins, p16(INK4a) and p14(ARF). Rare mutations in CDK4 have also been linked to the disease. Although the CDKN2A gene has been shown to be the major melanoma predisposing gene, there remains a significant proportion of melanoma kindreds linked to 9p21 in which germline mutations of CDKN2A have not been identified through direct exon sequencing. The purpose of this study was to assess the contribution of large rearrangements in CDKN2A to the disease in melanoma-prone families using multiplex ligation-dependent probe amplification. We examined 214 patients from independent pedigrees with at least two CMM cases. All had been tested for CDKN2A and CDK4 point mutation, and 47 were found positive. Among the remaining 167 negative patients, one carried a novel genomic deletion of CDKN2A exon 2. Overall, genomic deletions represented 2.1% of total mutations in this series (1 of 48), confirming that they explain a very small proportion of CMM susceptibility. In addition, we excluded a new gene on 9p21, KLHL9, as being a major CMM gene.

Awakening cortisol response in relation to psychosocial profiles and eating behaviors.

Awakening cortisol response was measured in 78 men and women, on 3 mornings within a 2-month period. Psychosocial and eating behavior variables were assessed using self-administered questionnaires on anxiety (State-Trait Anxiety Inventory), depression (Beck Depression Inventory), body esteem (Body Esteem Scale for Adolescents and Adults), and eating behaviors (Three-Factor Eating Questionnaire and Eating Disorder Inventory-2). Data on food intake and appetite sensations were also collected using a buffet-type meal test, a 3-day food record and visual analog scales measured before and after a standardized breakfast meal test. In women, high anxiety, disinhibition and hunger scores, as well as poor body esteem and a high weight preoccupation, were negatively correlated to ACR. The factor that appeared to account the most for this inverse relation was emotional susceptibility to disinhibition (r=-0.61, p=0.003). The latter was also negatively associated with the satiety quotient for fullness in response to the standardized breakfast (r=-0.48, p=0.010). In men, ACR was negatively associated with flexible (r=-0.33, p=0.020) and strategic (r=-0.28, p=0.049) restraint behaviors. This study highlights a gender-dependent relationship between ACR, hence the activity of the hypothalamic-pituitary-adrenal axis, and eating behaviors and psychological profiles.

Statistical analysis of CDR3 length distributions for the assessment of T and B cell repertoire biases.

Complementarity-determining region 3 (CDR3) length distribution analysis explores the diversity of the T cell receptor (TCR) and immunoglobulin (Ig) repertoire at the transcriptome level. Studies of the CDR3, the most hypervariable part of these molecules, have been frequently used to identify recruitment of T and B cell clones involved in immunological responses. CDR3 length distribution analysis gives a clear perception of repertoire variations between individuals and over time. However, the complexity of CDR3 length distribution patterns and the high number of possible repertoire alterations per individual called for the development of robust data analysis methods. The goal of these methods is to identify, quantify and statistically assess differences between repertoires so as to offer a better diagnostic or predictive tool for pathologies involving the immune system. In this review we will explain the benefit of analyzing CDR3 length distribution for the study of immune cell diversity. We will start by describing this technology and its associated data processing, and will subsequently focus on the statistical methods used to compare CDR3 length distribution patterns. Finally, we will address the various methods for assessing CDR3 length distribution gene signatures in pathological states.