Evidence For Deviations Research Articles

Measuring CP violation in b→cτ−ν¯τ using excited charm mesons

There is growing evidence for deviation from the standard model predictions in the ratios between semi-tauonic and semi-leptonic $B$ decays, known as the $R(D^{(*)})$ puzzle. If the source of this non-universality is new physics, it is natural to assume that it also breaks CP symmetry. In this paper we study the possibility of measuring CP violation in semi-tauonic $B$ decays, exploiting interference between excited charm mesons. Given the current values of $R(D^{(*)})$, we find that our proposed CP-violation observable could be as large as about 10%. We discuss the experimental advantages of our method and propose carrying it out at Belle II and LHCb.

HST Follow-up Observations of Two Bright z ∼ 8 Candidate Galaxies from the BoRG Pure-parallel Survey

Abstract We present follow-up imaging of two bright (L > L*) galaxy candidates at z ≳ 8 from the Brightest of Reionizing Galaxies (BoRG) survey with the F098M filter on the Hubble Space Telescope/Wide Field Camera 3 (HST/WFC3). The F098M filter provides an additional constraint on the flux blueward of the spectral break, and the observations are designed to discriminate between low- and high-z photometric redshift solutions for these galaxies. Our results confirm one galaxy, BoRG_0116+1425_747, as a highly probable z ∼ 8 source, but reveal that BoRG_0116+1425_630—previously the brightest known z > 8 candidate (m AB = 24.5)—is likely to be a z ∼ 2 interloper. As this source was substantially brighter than any other z > 8 candidate, removing it from the sample has a significant impact on the derived UV luminosity function in this epoch. We show that while previous BoRG results favored a shallow power-law decline in the bright end of the luminosity function prior to reionization, there is now no evidence for departure from a Schechter function form and therefore no evidence for a difference in galaxy formation processes before and after reionization.

RETRACTED ARTICLE: Forensic characterization of 15 autosomal STRs in four populations from Xinjiang, China, and genetic relationships with neighboring populations

The Xinjiang Uyghur Autonomous Region of China (XUARC) harbors 47 ethnic groups including the Manchu (MCH: 0.11%), Mongols (MGL: 0.81%), Kyrgyz (KGZ: 0.86%) and Uzbek (UZK: 0.066%). To establish DNA databases for these populations, allele frequency distributions for 15 autosomal short tandem repeat (STR) loci were determined using the AmpFlSTR Identifiler PCR amplification kit. There was no evidence of departures from Hardy–Weinberg equilibrium (HWE) in any of the four populations and minimal departure from linkage equilibrium (LE) for a very small number of pairwise combinations of loci. The probabilities of identity for the different populations ranged from 1 in 1.51 × 1017 (MCH) to 1 in 9.94 × 1018 (MGL), the combined powers of discrimination ranged from 0.99999999999999999824 (UZK) to 0.9999999999999999848 (MCH) and the combined probabilities of paternal exclusion ranged from 0.9999979323 (UZK) to 0.9999994839 (MCH). Genetic distances, a phylogenetic tree and principal component analysis (PCA) revealed that the MCH, KGZ and UZK are genetically closer to the Han population of Liaoning and the Mongol population of Mongolia while the MGL are closer to Han, Japanese, Korean, Malaysian, Hong Kong Han and Russians living in China.

Liver stiffness measurement predicted liver‐related events and all‐cause mortality: A systematic review and nonlinear dose–response meta‐analysis [RETRACTED

Numerous studies have investigated the prognosis value of the liver stiffness measurement (LSM) by transient elastography in assessing the risk of liver‐related events (LREs) and all‐cause mortality in patients with chronic liver disease (CLD). However, the shape of the dose–response relationship between them remains unclear. We searched PubMed, Embase, the Cochrane Library, and reference lists of articles for studies published up to July 1, 2017, that assessed the LSM in predicting LREs and all‐cause mortality among subjects with CLD. Fifty‐four observational cohort studies with 35,249 participants were included. Summary relative risks (RRs) were calculated using a random‐effects model, and a restricted cubic spline function was used to model the dose–response association. LREs and all‐cause mortality were increased in subjects with a high LSM (LRE: RR, 7.90; 95% confidence interval [CI], 5.65, 11.05; I 2 = 71.6%; all‐cause mortality: RR, 4.15; 95% CI, 2.56, 6.72; I 2 = 68.5%). For each unit increment of liver stiffness, the summary RR was 1.06 (95% CI, 1.06, 1.07; I 2 = 74.6%) for LREs and 1.06 (95% CI, 1.04, 1.07; I 2 = 55.7%) for all‐cause mortality. A positive relationship with a nonlinear trend for LSM with LREs and all‐cause mortality was examined by a dose–response meta‐analysis (P < 0.001). When stratified by etiology, a nonlinear association was also found in patients infected with hepatitis C virus and those coinfected with hepatitis C virus and human immunodeficiency virus. In contrast, there was no evidence of departure from linearity among patients with hepatitis B virus infection (P nonlinearity = 0.072). Conclusion: LSM is useful in screening LREs and all‐cause mortality in patients with CLD. Further studies are warranted in assessing the application of LSM in monitoring the risk of LREs and all‐cause mortality in clinical practice. (Hepatology Communications 2018;2:467‐476)

Joint associations of a polygenic risk score and environmental risk factors for breast cancer in the Breast Cancer Association Consortium.

Polygenic risk scores (PRS) for breast cancer can be used to stratify the population into groups at substantially different levels of risk. Combining PRS and environmental risk factors will improve risk prediction; however, integrating PRS into risk prediction models requires evaluation of their joint association with known environmental risk factors. Analyses were based on data from 20 studies; datasets analysed ranged from 3453 to 23 104 invasive breast cancer cases and similar numbers of controls, depending on the analysed environmental risk factor. We evaluated joint associations of a 77-single nucleotide polymorphism (SNP) PRS with reproductive history, alcohol consumption, menopausal hormone therapy (MHT), height and body mass index (BMI). We tested the null hypothesis of multiplicative joint associations for PRS and each of the environmental factors, and performed global and tail-based goodness-of-fit tests in logistic regression models. The outcomes were breast cancer overall and by estrogen receptor (ER) status. The strongest evidence for a non-multiplicative joint associations with the 77-SNP PRS was for alcohol consumption (P-interaction = 0.009), adult height (P-interaction = 0.025) and current use of combined MHT (P-interaction = 0.038) in ER-positive disease. Risk associations for these factors by percentiles of PRS did not follow a clear dose-response. In addition, global and tail-based goodness of fit tests showed little evidence for departures from a multiplicative risk model, with alcohol consumption showing the strongest evidence for ER-positive disease (P = 0.013 for global and 0.18 for tail-based tests). The combined effects of the 77-SNP PRS and environmental risk factors for breast cancer are generally well described by a multiplicative model. Larger studies are required to confirm possible departures from the multiplicative model for individual risk factors, and assess models specific for ER-negative disease.

Fertility Desires and the Course of Fertility Decline in sub‐Saharan Africa

This research has two main goals: (i) to examine fertility desires (number of children) in sub-Saharan Africa: levels as compared to other major regions and recent trends; and (ii) to assess the extent to which fertility decline in sub-Saharan Africa is contingent on decline in fertility desires (singly and in combination with other reproductive changes).

Sex ratio and spatial distribution of pistillate and staminate plants of Dasylirion cedrosanum

The genus Dasylirion forms a group of well-representedperennial, dioecious species called “sotoles” in Mexico. This genus is amain component of the arid lands of northern Mexico and southernUnited States, and plays important ecological and economic roles.Four D. cedrosanum populations from northeastern Mexico were surveyedto gather statistics related to sex ratios and spatial distribution.The statistics were performed on an unbiased sample of 448 plants.Tests for sex ratio and spatial distribution were carried out. No evidenceof departure from a 1:1 sex ratio proportion was found, both atthe global level and within sampling sites. Patterns of spatial sex segregationwere absent for all locations. One plant in the global samplecould not be classified either as male or female, being anatomicallyandromonoecious. Both, the staminate and hermaphroditic flowersof this plant produced well-developed pollen. However, the hermaphroditicflowers were unable to produce fruits, even in the presenceof pollen sources. The results are consistent with the expectedfor a well-established dioecious condition at the evolutionary scale,without environmental influences affecting the sex proportions andtheir spatial distribution.

Genetic modifiers of CHEK2*1100delC-associated breast cancer risk.

PurposeCHEK2*1100delC is a founder variant in European populations conferring a 2–3 fold increased risk of breast cancer (BC). Epidemiologic and family studies have suggested that the risk associated with CHEK2*1100delC is modified by other genetic factors in a multiplicative fashion. We have investigated this empirically using data from the Breast Cancer Association Consortium (BCAC).MethodsWith genotype data of 39,139 (624 1100delC carriers) BC patients and 40,063 (224) healthy controls from 32 BCAC studies, we analyzed the combined risk effects of CHEK2*1100delC and 77 common variants in terms of a polygenic risk score (PRS) and pairwise interaction.ResultsThe PRS conferred an odds ratio (OR) of 1.59 [95% CI 1.21–2.09] per standard deviation for BC for CHEK2*1100delC carriers and 1.58 [1.55–1.62] for non-carriers. No evidence for deviation from the multiplicative model was found. The OR for the highest quintile of the PRS was 2.03 [0.86–4.78] for CHEK2*1100delC carriers placing them to the high risk category according to UK NICE guidelines. OR for the lowest quintile was 0.52 [0.16–1.74], indicating life-time risk close to population average.ConclusionOur results confirm the multiplicative nature of risk effects conferred by CHEK2*1100delC and the common susceptibility variants. Furthermore, the PRS could identify the carriers at a high life-time risk for clinical actions.

Allele frequencies of 15 autosomal STR loci in the Caymanian population.

Allele frequency distributions in the Caymanian population were determined using the AmpFlSTR® Identifiler® PCR amplification kit. Little evidence of departure from Hardy-Weinberg equilibrium or the association of alleles of different loci was detected. Comparison with relevant population groups supports the Caymanian population having a distinct allelic distribution. The 15 Identifiler® loci provide combined power of discrimination and exclusion values of 0.999999999999999995 and 0.9999992, respectively, proving suitable for the forensic and paternity testing requirements of the Cayman Islands.

The expansion rate of the intermediate universe in light of Planck

Abstract We use cosmology-independent measurements of the expansion history in the redshift range 0.1 ≲ z 1.2 and compare them with the Cosmic Microwave Background-derived expansion history predictions. The motivation is to investigate if the tension between the local (cosmology independent) Hubble constant H 0 value and the Planck-derived H 0 is also present at other redshifts. We conclude that there is no tension between Planck and cosmology independent-measurements of the Hubble parameter H ( z ) at 0.1 ≲ z 1.2 for the Λ CDM model (odds of tension are only 1:15, statistically not significant). Considering extensions of the Λ CDM model does not improve these odds (actually makes them worse), thus favouring the simpler model over its extensions. On the other hand the H ( z ) data are also not in tension with the local H 0 measurements but the combination of all three data-sets shows a highly significant tension (odds ∼1:400). Thus the new data deepen the mystery of the mismatch between Planck and local H 0 measurements, and cannot univocally determine whether it is an effect localised at a particular redshift. Having said this, we find that assuming the NGC4258 maser distance as the correct anchor for H 0 , brings the odds to comfortable values. Further, using only the expansion history measurements we constrain, within the Λ CDM model, H 0 = 68.5 ± 3.5 and Ω m = 0.32 ± 0.05 (at 68% confidence) without relying on any CMB prior. We also address the question of how smooth the expansion history of the Universe is given the cosmology independent data and conclude that there is no evidence for deviations from smoothness on the expansion history, neither variations with time in the value of the equation of state of dark energy.

Legal Briefs: Late-Onset Group B Streptococcus Meningitis: Should It Happen in a Newborn Intensive Care Unit?

* Abbreviations: BP; : blood pressure CBC; : complete blood cell CNS; : central nervous system EOGBS; : early-onset group B Streptococcus GBS; : group B Streptococcus HR; : heart rate IAP; : intrapartum antibiotic prophylaxis ID; : infectious disease LOGBS; : late-onset group B Streptococcus A 28-6/7-weeks'-gestational-age boy whose birthweight was 1,340 g was born to a 32-year-old G3P0 woman whose pregnancy was complicated by a short cervix and preterm labor. Two cervical cultures and 1 urine culture were positive for group B Streptococcus (GBS), the latest positive cervical culture taken 2 days before delivery. Antibiotics were not given despite preterm labor with a positive GBS culture and bacteriuria. The infectious disease (ID) consult retained by the plaintiff was critical of this omission. The mother was given magnesium sulfate for tocolysis and antenatal steroids. An emergency cesarean delivery was performed because of heart rate (HR) decelerations down to the 70s for 6 to 7 minutes. At the time of delivery, membranes were ruptured and clear fluid was found. Apgar scores were 91 and 105. The GBS status was documented “unknown” in the delivery and neonatal records and remained unknown throughout the infant’s hospital stay. The plaintiff ID expert was critical of the physicians caring for the infant because he felt they should have become aware of the maternal GBS status . The treating neonatologists pointed out that nothing would have been done differently for the infant with that knowledge because the infant ’ s blood culture was sent and he was given empiric antibiotic. Continuous positive airway pressure was started immediately after birth, but because respiratory distress syndrome developed, he was intubated and given poractant alfa (Curosurf; Cornerstone Therapeutics, Inc, Cary, NC). The infant was extubated a few hours later and remained on room air for 1 month, initially with nasal continuous positive airway pressure, then nasal cannula. The blood culture was negative, and complete blood cell (CBC) count was normal. Ampicillin and gentamicin were discontinued after 2 days. His baseline HRs averaged 146 beats per minute until caffeine was started. Then …

Allele frequency data of 15 autosomal STR loci in four major population groups of South Africa

Allele frequency distributions for 15 tetrameric short tandem repeat (STR) loci were determined using the AmpFlSTR® Identifiler Plus™ PCR amplification kit. There was little evidence of departures from Hardy-Weinberg equilibrium or association of alleles of different loci in the population samples. The probability of identity values for the different populations range from 1/3.3 × 10(17) (White) to 1/1.88 × 10(18) (Coloured). The combined probability of paternal exclusion for the different population groups ranges from 0.9995858 (Coloured) to 0.9997874 (Indian).

Azithromycin To Prevent Bronchopulmonary Dysplasia in Ureaplasma-Infected Preterm Infants: Pharmacokinetics, Safety, Microbial Response, and Clinical Outcomes with a 20-Milligram-per-Kilogram Single Intravenous Dose

Ureaplasma respiratory tract colonization is associated with bronchopulmonary dysplasia (BPD) in preterm infants. Previously, we demonstrated that a single intravenous (i.v.) dose of azithromycin (10 mg/kg of body weight) is safe but inadequate to eradicate Ureaplasma spp. in preterm infants. We performed a nonrandomized, single-arm open-label study of the pharmacokinetics (PK) and safety of intravenous 20-mg/kg single-dose azithromycin in 13 mechanically ventilated neonates with a gestational age between 24 weeks 0 days and 28 weeks 6 days. Pharmacokinetic data from 25 neonates (12 dosed with 10 mg/kg i.v. and 13 dosed with 20 mg/kg i.v.) were analyzed using a population modeling approach. Using a two-compartment model with allometric scaling of parameters on body weight (WT), the population PK parameter estimates were as follows: clearance, 0.21 liter/h × WT(kg)(0.75) [WT(kg)(0.75) indicates that clearance was allometrically scaled on body weight (in kilograms) with a fixed exponent of 0.75]; intercompartmental clearance, 2.1 liters/h × WT(kg)(0.75); central volume of distribution (V), 1.97 liters × WT (kg); and peripheral V, 17.9 liters × WT (kg). There was no evidence of departure from dose proportionality in azithromycin exposure over the tested dose range. The calculated area under the concentration-time curve over 24 h in the steady state divided by the MIC90 (AUC24/MIC90) for the single dose of azithromycin (20 mg/kg) was 7.5 h. Simulations suggest that 20 mg/kg for 3 days will maintain azithromycin concentrations of >MIC50 of 1 μg/ml for this group of Ureaplasma isolates for ≥ 96 h after the first dose. Azithromycin was well tolerated with no drug-related adverse events. One of seven (14%) Ureaplasma-positive subjects and three of six (50%) Ureaplasma-negative subjects developed physiologic BPD. Ureaplasma was eradicated in all treated Ureaplasma-positive subjects. Simulations suggest that a multiple-dose regimen may be efficacious for microbial clearance, but the effect on BPD remains to be determined.

Isolation and characterization of eight polymorphic microsatellite loci for Natterer’s bat, Myotis nattereri (Vespertilionidae, Chiroptera)

Eight new microsatellite loci were isolated and characterized for the Natterer’s bat Myotis nattereri from a microsatellite-enriched genomic library. The usefulness of these markers was assessed by screening a sample comprising 100 specimens collected from throughout the species range in Europe. Both moderately and highly polymorphic loci were identified with 3–17 alleles segregating per locus (mean 8.1 SE ± 0.048). No evidence for departure from HWE or linkage disequilibrium among loci was observed. These markers will provide a valuable addition to the molecular toolbox currently available for studies of population genetic structure, parentage and social organisation of M. nattereri and related species.

High potential for using DNA from ancient herring bones to inform modern fisheries management and conservation.

Pacific herring (Clupea pallasi) are an abundant and important component of the coastal ecosystems for the west coast of North America. Current Canadian federal herring management assumes five regional herring populations in British Columbia with a high degree of exchange between units, and few distinct local populations within them. Indigenous traditional knowledge and historic sources, however, suggest that locally adapted, distinct regional herring populations may have been more prevalent in the past. Within the last century, the combined effects of commercial fishing and other anthropogenic factors have resulted in severe declines of herring populations, with contemporary populations potentially reflecting only the remnants of a previously more abundant and genetically diverse metapopulation. Through the analysis of 85 archaeological herring bones, this study attempted to reconstruct the genetic diversity and population structure of ancient herring populations using three different marker systems (mitochondrial DNA (mtDNA), microsatellites and SNPs). A high success rate (91%) of DNA recovery was obtained from the extremely small herring bone samples (often <10 mg). The ancient herring mtDNA revealed high haplotype diversity comparable to modern populations, although population discrimination was not possible due to the limited power of the mtDNA marker. Ancient microsatellite diversity was also similar to modern samples, but the data quality was compromised by large allele drop-out and stuttering. In contrast, SNPs were found to have low error rates with no evidence for deviations from Hardy-Weinberg equilibrium, and simulations indicated high power to detect genetic differentiation if loci under selection are used. This study demonstrates that SNPs may be the most effective and feasible approach to survey genetic population structure in ancient remains, and further efforts should be made to screen for high differentiation markers.This study provides the much needed foundation for wider scale studies on temporal genetic variation in herring, with important implications for herring fisheries management, Aboriginal title rights and herring conservation.

Isolation and characterization of nine microsatellite loci in a Malagasy endemic rodent, Eliurus carletoni (Rodentia: Nesomyinae)

We developed microsatellite markers for the recently described forest rodent, Eliurus carletoni, from an enriched genomic library. Nine loci composed of four dinucleotide, one trinucleotide, one tetranucleotide and three compound repeats were isolated and characterized using two wild populations. One locus was found to be monomorphic. For the polymorphic loci, the average number of alleles per locus was 7.13 and 8.38 for each population. Mean expected and observed heterozygosities were high (i.e. 0.76 and 0.80). Tests for linkage disequilibrium were not significant across all locus pairs. One locus tested significant for null alleles, but only one population exhibited a significant deviation from the Hardy–Weinberg Equilibrium (HWE) at this locus. All remaining loci show no evidence of departure from HWE. Overall, we identified eight polymorphic loci that may be used in conservation and population genetics studies of E. carletoni.

Impact of polymorphic variation at 7p15.3, 3p22.1 and 2p23.3 loci on risk of multiple myeloma

Impact of polymorphic variation at 7p15.3, 3p22.1 and 2p23.3 loci on risk of multiple myeloma

Isolation and characterization of new polymorphic microsatellite markers for the tick Ixodes ricinus (Acari, Ixodidae)

Nine microsatellite markers were isolated from unfed larvae of Ixodes ricinus and were tested on two populations of nymphs collected on roe deer (N=21) and birds (N=39) in a French suburban forest. All markers were polymorphic, with limited evidence for deviations from linkage equilibrium. In accordance with previous markers developed for this species, we found large heterozygote deficits for six of the nine loci. Deficits were of the same order of magnitude within a tick infrapopulation, suggesting that population-level estimates were not due to a Wahlund effect among individual hosts, but more likely to technical problems (i.e., null alleles due to mutations in the flanking regions of the microsatellites). Although micro-geographic substructure (e.g., homogamy within infrapopulations) can not be ruled out, it is possible that null alleles could be an inherent problem associated with this tick species and specific genome-level studies are called for. Despite the possible presence of null alleles, the precision of population genetic estimates was improved by the addition of the newly-developed markers making them a useful addition for studying the population ecology of I. ricinus.

Response to Grant, WB: “Ultraviolet exposure and non-Hodgkin’s lymphoma: beneficial and adverse effects?”

As we discussed in our recent manuscript, our findings of modest but significant positive associations between ambient ultraviolet (UV) radiation and non-Hodgkin lymphoma (NHL) risk in the Nurses’ Health Study (NHS) were unexpected and inconsistent with most of the prior literature on this topic [1]. Dr. Grant offers alternative explanations for our results. In response to his comments, we have conducted additional data analyses. First, Dr. Grant questions whether a majority of NHS participants reside in regions of relatively low total and UV-B radiation. We agree that results from the NHS may not be generalizable to other populations, particularly those in the areas of higher UV radiation. Because nurses originally were recruited from 11 US states (i.e., California, Connecticut, Florida, Maryland, Massachusetts, Michigan, New Jersey, New York, Ohio, Pennsylvania, and Texas) [2], a majority of participants (59%) resided in the Northeast at baseline in 1976. A similar proportion of women reported Northeast residence at birth, age 15, and age 30. Over the course of 30 years of follow-up, 55% of the person-time included residence in the northeast region of the USA. We used the distribution of average annual UV-B flux values in our study population, which ranged from 93 to 196 (in R-B counts 910) as nurses changed residence over the 30 years of follow-up, to guide our choice of cutpoints for analysis. We reported that NHL risk was increased among women who resided in regions with UV-B flux[113 compared to those with lower exposure (\113) [1]. In response to Dr. Grant’s comment, we dichotomized the top category of UV-flux at its median value (164) and re-analyzed the data using this 4-category variable. Our findings were similar to the results presented in the manuscript, with increased risks most apparent in the highest category of ambient UV-B exposure. For example, the multivariable-adjusted rate ratio (RR) for NHL associated with UV-B flux [164 at age 15, which included residence in Texas, Florida, Arizona, New Mexico, and Louisiana, compared to UV-B flux\113 was 1.72 (95% confidence interval (CI): 1.30, 2.29). Further, it is important to note that we observed statistically significant linear trends for the association of average annual UV-B flux, assessed at various time points and considered as a continuous variable, and risk of NHL (p-trend\0.05). Moreover, we found no evidence of departure from linearity when restricted cubic splines were examined. Second, Dr. Grant suggests that the association between UV-B radiation and NHL risk may differ by latitude because of differences in the relative amount of UV-B and UV-A radiation. We speculated in our paper that increased risks of NHL could plausibly be mediated through immunosuppressive effects of UV exposure. As previously discussed, modest increased risks were most apparent for individuals living in areas of higher UV-B radiation (i.e., outside of the northeast). Unfortunately, data on ambient UV-A levels were not available for analysis, and therefore, we could not evaluate the relative effects of UV-A vs. UV-B exposure nor could we directly evaluate the immunosuppression K. A. Bertrand (&) F. Laden Department of Epidemiology, Harvard School of Public Health, 677 Huntington Avenue, Boston, MA 02115, USA e-mail: kbertran@hsph.harvard.edu

Chromosome X markers DXS6795, DXS9907 and GATA144D04: Repeat structure and allele distribution in a German population

The STR markers DXS6795, DXS9907 and GATA144D04 are located on the short arm in the region Xp22.11–Xp11.23. These loci were typed from buccal swab samples from unrelated German individuals (161 male, 362 female). Additionally, DNA from 90 males with one ore more daughters and their 135 grandsons were typed to check for mutability of these loci. German population and sequencing data for these three loci as well as statistical parameters of forensic interest are presented. DNA typing patterns of cell lines were used as intra- and inter-laboratory standards to calibrate allelic ladders. We found 8 different alleles in DXS9907 and GATA144D04, whereas DXS6795 exhibited only 6 alleles. Allelic distribution patterns are identical for males and females. There is no evidence for deviation from the Hardy–Weinberg equilibrium in female samples. Furthermore, no mutations were detected within 90 paternal and 135 maternal meioses. The three microsatellites are moderately variable with PIC values of 0.61, 0.56 and 0.70.