Perturbation expansions of multilocus fixation probabilities for frequency-dependent selection with applications to the Hill-Robertson effect and to the joint evolution of helping and punishment.

Natural populations are of finite size and organisms carry multilocus genotypes. There are, nevertheless, few results on multilocus models when both random genetic drift and natural selection affect the evolutionary dynamics. In this paper we describe a formalism to calculate systematic perturbation expansions of moments of allelic states around neutrality in populations of constant size. This allows us to evaluate multilocus fixation probabilities (long-term limits of the moments) under arbitrary strength of selection and gene action. We show that such fixation probabilities can be expressed in terms of selection coefficients weighted by mean first passages times of ancestral gene lineages within a single ancestor. These passage times extend the coalescence times that weight selection coefficients in one-locus perturbation formulas for fixation probabilities. We then apply these results to investigate the Hill-Robertson effect and the coevolution of helping and punishment. Finally, we discuss limitations and strengths of the perturbation approach. In particular, it provides accurate approximations for fixation probabilities for weak selection regimes only (Ns < or = 1), but it provides generally good prediction for the direction of selection under frequency-dependent selection.

Frequency and characteristics of familial melanoma in Spain: the FAM-GEM-1 Study.

INTRODUCTION Familial history of melanoma is a well-known risk factor for the disease, and 7% melanoma patients were reported to have a family history of melanoma. Data relating to the frequency and clinical and pathological characteristics of both familial and non-familial melanoma in Spain have been published, but these only include patients from specific areas of Spain and do not represent the data for the whole of Spain. PATIENTS AND METHODS An observational study conducted by the Spanish Group of Melanoma (GEM) analyzed the family history of patients diagnosed with melanoma between 2011 and 2013 in the dermatology and oncology departments. RESULTS In all, 1047 patients were analyzed, and 69 (6.6%) fulfilled criteria for classical familial melanoma (two or more first-degree relatives diagnosed with melanoma). Taking into account other risk factors for familial melanoma, such as multiple melanoma, pancreatic cancer in the family or second-degree relatives with melanoma, the number of patients fulfilling the criteria increased to 165 (15.8%). Using a univariate analysis, we determined that a Breslow index of less than 1 mm, negative mitosis, multiple melanoma, and a history of sunburns in childhood were more frequent in familial melanoma patients, but a multivariate analysis revealed no differences in any pathological or clinical factor between the two groups. CONCLUSIONS Similar to that observed in other countries, familial melanoma accounts for 6.6% of melanoma diagnoses in Spain. Although no differences in the multivariate analysis were found, some better prognosis factors, such as Breslow index, seem more frequent in familial melanoma, which reflect a better early detection marker and/or a different biological behavior.

The efficiency of antigen recognition by CD8+ CTL clones is determined by the frequency of serial TCR engagement.

Using H-2Kd-restricted CTL clones, which are specific for a photoreactive derivative of the Plasmodium berghei circumsporozoite peptide PbCS(252-260) (SYIPSAEKI) and permit assessment of TCR-ligand interactions by TCR photoaffinity labeling, we have previously identified several peptide derivative variants for which TCR-ligand binding and the efficiency of Ag recognition deviated by fivefold or more. Here we report that the functional CTL response (cytotoxicity and IFN-gamma production) correlated with the rate of TCR-ligand complex dissociation, but not the avidity of TCR-ligand binding. While peptide antagonists exhibited very rapid TCR-ligand complex dissociation, slightly slower dissociation was observed for strong agonists. Conversely and surprisingly, weak agonists typically displayed slower dissociation than the wild-type agonists. Acceleration of TCR-ligand complex dissociation by blocking CD8 participation in TCR-ligand binding increased the efficiency of Ag recognition in cases where dissociation was slow. In addition, permanent TCR engagement by TCR-ligand photocross-linking completely abolished sustained intracellular calcium mobilization, which is required for T cell activation. These results indicate that the functional CTL response depends on the frequency of serial TCR engagement, which, in turn, is determined by the rate of TCR-ligand complex dissociation.

Insuffisance rénale terminale d'origine lithiasique : fréquence, causes et prévention [Nephrolithiasis-induced ESRD: frequency, causes and prevention].

Nephrolithiasis still remains a too frequent - and under-appreciated - cause of end-stage renal disease (ESRD), and this is all the most unfortunate since such an untoward course is now preventable in most cases. Among 1391 patients who started maintenance dialysis at Necker hospital between 1989 and 2000, nephrolithiasis was identified as the cause of ESRD in 45 of them, an overall prevalence of 3.2%. Infection stones accounted for 42.2% of cases, calcium stones for 26.7%, uric acid stones for 17.8% and hereditary diseases for 13.3%. The proportion of nephrolithiasis-associated ESRD declined from 4.7% to 2.2% from the 1989-1991 to the 1998-2000 period, as a result of the decreased incidence of ESRD in patients with infection and calcium nephrolithiasis. Based on our observations and on published reports, it emerges that most cases of nephrolithiasis-associated ESRD were due to sub-optimal management (especially in the case of infection or cystine stones) or to late (or erroneous) etiologic diagnosis, precluding early institution of appropriate therapeutic measures. In particular, several patients with primary hyperoxaluria or 2,8-dihydroxyadeninuria were diagnosed while already on dialysis or after unsuccessful kidney transplantation, due to wrong initial diagnosis. In conclusion, thanks to recent advances in diagnosis and management of stone formers, ESRD should now be prevented in the great majority of patients, at the condition of early etiologic diagnosis based on accurate morphoconstitutional analysis of calculi and metabolic evaluation, and early implementation of appropriate preventive medical treatment.

Simple finite field method for calculation of static and dynamic vibrational hyperpolarizabilities: curvature contributions

In the static field limit, the vibrational hyperpolarizability consists of two contributions due to: (1) the shift in the equilibrium geometry (known as nuclear relaxation), and (2) the change in the shape of the potential energy surface (known as curvature). Simple finite field methods have previously been developed for evaluating these static field contributions and also for determining the effect of nuclear relaxation on dynamic vibrational hyperpolarizabilities in the infinite frequency approximation. In this paper the finite field approach is extended to include, within the infinite frequency approximation, the effect of curvature on the major dynamic nonlinear optical processes

Nuclear relaxation contribution to static and dynamic (infinite frequency approximation) nonlinear optical properties by means of electrical property expansions: Application to HF, CH4, CF4, and SF6

Electrical property derivative expressions are presented for the nuclear relaxation contribution to static and dynamic (infinite frequency approximation) nonlinear optical properties. For CF4 and SF6, as opposed to HF and CH4, a term that is quadratic in the vibrational anharmonicity (and not previously evaluated for any molecule) makes an important contribution to the static second vibrational hyperpolarizability of CF4 and SF6. A comparison between calculated and experimental values for the difference between the (anisotropic) Kerr effect and electric field induced second-harmonic generation shows that, at the Hartree-Fock level, the nuclear relaxation/infinite frequency approximation gives the correct trend (in the series CH4, CF4, SF6) but is of the order of 50% too small

Epidemiology of inflammatory bowel disease: Is there a shift towards onset at a younger age?

OBJECTIVES: Increasing numbers of paediatric and adolescent patients with Crohn disease (CD) and ulcerative colitis (UC) are reported. To determine whether this observation is a consequence of a shift towards onset at a younger age, we analysed retrospective data from patients enrolled in the Swiss IBD Cohort Study (SIBDCS). PATIENTS AND METHODS: The SIBDCS is a disease-based cohort in Switzerland, which collects retrospective and prospective data on a large sample of patients with inflammatory bowel disease (IBD). Patients, diagnosed from 1980, were stratified according to diagnosis of CD and UC. Age at disease onset (age at first symptoms and age at diagnosis) was analysed in relation to calendar year of disease onset. Data were extracted from physician and patient questionnaires. Linear regressions of age at disease onset by calendar year of disease onset adjusted by sex, country of birth, and education were performed. RESULTS: Adjusted regression coefficients for CD and UC were significantly positive, that is, age at disease onset has increased with time. Male sex was associated with an increase in age at disease onset, and birth in Switzerland with a decrease. These associations were statistically significant. CONCLUSIONS: The results from the SIBDCS do not support the hypothesis that disease onset of both CD and UC occur today at a younger age. On the contrary, our results show that there is a significant trend for age at disease onset occurring at an older age today as compared with recent decades. We conclude that the observation of increasing numbers of paediatric and adolescent patients with IBD is not caused by a trend towards disease onset at a younger age, but that this may rather be a consequence of the overall increasing incidence of these conditions.

Radio Frequency Identification Tagging as a Mechanism of Creating a Viable Producer’s Brand in the Cattle Industry, May 2005

This manuscript reports on a project to examine the feasibility of extensive radio frequency identification (RFID) tagging to determine product provenance in the meat production industry. The investigators examined existing technologies and meat production processes as well as emerging technologies in RFID tagging to assess the potential of RFID technologies for provenance assurance. While RFID technologies hold tremendous promise for traceability, the current state of the technology and production process creates challenges for effectively creating full traceability. However, RFID holds tremendous potential for improving processing throughput, which will help make RFIDbased traceability more attractive for adoption by meat processors.

Can fisheries-induced evolution shift reference points for fisheries management?

Biological reference points are important tools for fisheries management. Reference points are not static, but may change when a population's environment or the population itself changes. Fisheries-induced evolution is one mechanism that can alter population characteristics, leading to "shifting" reference points by modifying the underlying biological processes or by changing the perception of a fishery system. The former causes changes in "true" reference points, whereas the latter is caused by changes in the yardsticks used to quantify a system's status. Unaccounted shifts of either kind imply that reference points gradually lose their intended meaning. This can lead to increased precaution, which is safe, but potentially costly. Shifts can also occur in more perilous directions, such that actual risks are greater than anticipated. Our qualitative analysis suggests that all commonly used reference points are susceptible to shifting through fisheries-induced evolution, including the limit and "precautionary" reference points for spawning-stock biomass, Blim and Bpa, and the target reference point for fishing mortality, F0.1. Our findings call for increased awareness of fisheries-induced changes and highlight the value of always basing reference points on adequately updated information, to capture all changes in the biological processes that drive fish population dynamics.

Frequency and impact of autosomal dominant polycystic kidney disease in the Seychelles (Indian Ocean).

BACKGROUND: As little such data is available in African populations, we investigated the prevalence of ADPKD and the impact of the disease in the Seychelles islands, where approximately 65% of the population is of African descent and 30% of Caucasian or mixed descent. METHODS: Prevalent cases were identified over a 3-year period by requesting all the doctors in the country (most of them are employed within a national health system) to refer all presumed or confirmed cases and by systematically examining the family members of all confirmed cases. The diagnosis was based on standard criteria including ultrasonographic findings and family history. RESULTS: Forty-two cases were identified in this population of 74,331 inhabitants, a total prevalence (per 100,000 total population) of 57 (95% CI, 41-76). All but one of the cases were of Caucasian descent so that the prevalence rates of the disease in the populations of Black and Caucasian descents were respectively 2 (0-11) and 184 (132-249). The prevalence rates of the gene(s) carriers were estimated to be 75 (45-117) in the total population respectively 6 (0-33) and 236 (140-372) in the Black and Caucasian populations. Haplotype analysis in 58 cases from three families showed a common DNA fragment in all affected individuals. Cases had significantly higher blood pressure compared to the general population and 21% had serum creatinine higher than 120 mumol/l. Among the established pedigrees, mean age of death between 1960 and 1995 (haemodialysis was introduced in 1992) was younger in subjects with than those without ADPKD (50.5 vs 67.7 years; P < 0.001). CONCLUSIONS: In the Seychelles, ADPKD clusters in the Caucasian population (possibly a founder effect), is rare in individuals of black descent, and is associated with substantial clinical and survival impact.

Frequency and effects of meeting health-behavior guidelines among adolescents

Objective: To assess the relationship between overweight status and the concomitant adherence to physical activity, daily screen time, and nutritional guidelines. Methods: Data were derived from the Swiss HBSC survey 2006. Participants (n=8130, 48.7% girls) were divided into two groups: normal-weight (n=7215, 44.8% girls), and overweight (n=915, 34.8% girls), using self-reported height and weight. Groups were compared on adherence to physical activity, screen time and nutritional guidelines. Bivariate analyses were carried out followed by multivariate analyses using normal-weight individuals as the reference category. Results: Regardless of gender, overweight individuals reported more screen time, less physical activity, and less concomitant adherence to guidelines. For boys, the multivariate analysis showed that any amount exceeding screen time recommendations was associated with increased odds of being overweight (>2-4h: adjusted odds ratio (AOR)=l .40; >4-6h: AOR=l .48; >6h: AOR=l .83). A similar relation was found for any amount below physical activity recommendations (4-6 times a week: AOR=1.67; 2-3 times a week: AOR=1.87; once a week or less: AOR=2.1). For girls, not meeting nutritional guidelines was less likely among overweight individuals (0-2 recommendations: AOR=0.54). Regardless of weight status, more than half of adolescents did not comply with any guideline and less than 2% met all 3 at the same time. Conclusions: Meeting current nutritional, physical activity and screen time guidelines should be encouraged with respect to overweight. However, as extremely low rates of concomitant adherence were found regardless of weight status, their achievability is questionable (especially for nutrition) which warrants further research to better adapt them to adolescents.

Geographic variation in the frequency of isolation and fluconazole and voriconazole susceptibilities of Candida glabrata: an assessment from the ARTEMIS DISK Global Antifungal Surveillance Program.

Geographic differences in frequency and azole resistance among Candida glabrata may impact empiric antifungal therapy choice. We examined geographic variation in isolation and azole susceptibility of C. glabrata. We examined 23 305 clinical isolates of C. glabrata during ARTEMIS DISK global surveillance. Susceptibility testing to fluconazole and voriconazole was assessed by disk diffusion, and the results were grouped by geographic location: North America (NA) (2470 isolates), Latin America (LA) (2039), Europe (EU) (12 439), Africa and the Middle East (AME) (728), and Asia-Pacific (AP) (5629). Overall, C. glabrata accounted for 11.6% of 201 653 isolates of Candida and varied as a proportion of all Candida isolated from 7.4% in LA to 21.1% in NA. Decreased susceptibility (S) to fluconazole was observed in all geographic regions and ranged from 62.8% in AME to 76.7% in LA. Variation in fluconazole susceptibility was observed within each region: AP (range, 50-100% S), AME (48-86.9%), EU (44.8-88%), LA (43-92%), and NA (74.5-91.6%). Voriconazole was more active than fluconazole (range, 82.3-84.2% S) with similar regional variation. Among 22 sentinel sites participating in ARTEMIS from 2001 through 2007 (84 140 total isolates, 8163 C. glabrata), the frequency of C. glabrata isolation increased in 14 sites and the frequency of fluconazole resistance (R) increased in 11 sites over the 7-year period of study. The sites with the highest cumulative rates of fluconazole R were in Poland (22% R), the Czech Republic (27% R), Venezuela (27% R), and Greece (33% R). C. glabrata was most often isolated from blood, normally sterile body fluids and urine. There is substantial geographic and institutional variation in both frequency of isolation and azole resistance among C. glabrata. Prompt species identification and fluconazole susceptibility testing are necessary to optimize therapy for invasive candidiasis.

Wide-pulse-high-frequency neuromuscular stimulation of triceps surae induces greater muscle fatigue compared with conventional stimulation.

We compared the extent and origin of muscle fatigue induced by short-pulse-low-frequency [conventional (CONV)] and wide-pulse-high-frequency (WPHF) neuromuscular electrical stimulation. We expected CONV contractions to mainly originate from depolarization of axonal terminal branches (spatially determined muscle fiber recruitment) and WPHF contractions to be partly produced via a central pathway (motor unit recruitment according to size principle). Greater neuromuscular fatigue was, therefore, expected following CONV compared with WPHF. Fourteen healthy subjects underwent 20 WPHF (1 ms-100 Hz) and CONV (50 μs-25 Hz) evoked isometric triceps surae contractions (work/rest periods 20:40 s) at an initial target of 10% of maximal voluntary contraction (MVC) force. Force-time integral of the 20 evoked contractions (FTI) was used as main index of muscle fatigue; MVC force loss was also quantified. Central and peripheral fatigue were assessed by voluntary activation level and paired stimulation amplitudes, respectively. FTI in WPHF was significantly lower than in CONV (21,717 ± 11,541 vs. 37,958 ± 9,898 N·s P<0,001). The reductions in MVC force (WPHF: -7.0 ± 2.7%; CONV: -6.2 ± 2.5%; P < 0.01) and paired stimulation amplitude (WPHF: -8.0 ± 4.0%; CONV: -7.4 ± 6.1%; P < 0.001) were similar between conditions, whereas no change was observed for voluntary activation level (P > 0.05). Overall, our results showed a different motor unit recruitment pattern between the two neuromuscular electrical stimulation modalities with a lower FTI indicating greater muscle fatigue for WPHF, possibly limiting the presumed benefits for rehabilitation programs.