Genome-Wide Association Study in BRCA1 Mutation Carriers Identifies Novel Loci Associated with Breast and Ovarian Cancer Risk

BRCA1-associated breast and ovarian cancer risks can be modified by common genetic variants. To identify further cancer risk-modifying loci, we performed a multi-stage GWAS of 11,705 BRCA1 carriers (of whom 5,920 were diagnosed with breast and 1,839 were diagnosed with ovarian cancer), with a further replication in an additional sample of 2,646 BRCA1 carriers. We identified a novel breast cancer risk modifier locus at 1q32 for BRCA1 carriers (rs2290854, P = 2.7×10-8, HR = 1.14, 95% CI: 1.09-1.20). In addition, we identified two novel ovarian cancer risk modifier loci: 17q21.31 (rs17631303, P = 1.4×10-8, HR = 1.27, 95% CI: 1.17-1.38) and 4q32.3 (rs4691139, P = 3.4×10-8, HR = 1.20, 95% CI: 1.17-1.38). The 4q32.3 locus was not associated with ovarian cancer risk in the general population or BRCA2 carriers, suggesting a BRCA1-specific associat

Genetic variation at CYP3A is associated with age at menarche and breast cancer risk : a case-control study

Abstract Introduction We have previously shown that a tag single nucleotide polymorphism (rs10235235), which maps to the CYP3A locus (7q22.1), was associated with a reduction in premenopausal urinary estrone glucuronide levels and a modest reduction in risk of breast cancer in women age ≤50 years. Methods We further investigated the association of rs10235235 with breast cancer risk in a large case control study of 47,346 cases and 47,570 controls from 52 studies participating in the Breast Cancer Association Consortium. Genotyping of rs10235235 was conducted using a custom Illumina Infinium array. Stratified analyses were conducted to determine whether this association was modified by age at diagnosis, ethnicity, age at menarche or tumor characteristics. Results We confirmed the association of rs10235235 with breast cancer risk for women of European ancestry but found no evidence that this association differed with age at diagnosis. Heterozygote and homozygote odds ratios (ORs) were OR = 0.98 (95% CI 0.94, 1.01; P = 0.2) and OR = 0.80 (95% CI 0.69, 0.93; P = 0.004), respectively (P trend = 0.02). There was no evidence of effect modification by tumor characteristics. rs10235235 was, however, associated with age at menarche in controls (P trend = 0.005) but not cases (P trend = 0.97). Consequently the association between rs10235235 and breast cancer risk differed according to age at menarche (P het = 0.02); the rare allele of rs10235235 was associated with a reduction in breast cancer risk for women who had their menarche age ≥15 years (ORhet = 0.84, 95% CI 0.75, 0.94; ORhom = 0.81, 95% CI 0.51, 1.30; P trend = 0.002) but not for those who had their menarche age ≤11 years (ORhet = 1.06, 95% CI 0.95, 1.19, ORhom = 1.07, 95% CI 0.67, 1.72; P trend = 0.29). Conclusions To our knowledge rs10235235 is the first single nucleotide polymorphism to be associated with both breast cancer risk and age at menarche consistent with the well-documented association between later age at menarche and a reduction in breast cancer risk. These associations are likely mediated via an effect on circulating hormone levels

Residency and long-distance movements of sevengill sharks (Notorhynchus cepedianus) tagged in San Francisco Bay

Abstract Background Sevengill sharks are common inhabitants of estuaries and coastal areas and particularly abundant in San Francisco Bay (SFB). There is limited knowledge about the level of residency and migratory movements of this species. We describe the degree of residence of sevengill sharks in SFB and nearby locations, using ultrasonic tags and automated listening stations. Results Sevengills showed a high degree of residency in SFB, particularly to the Golden Gate (GG) area where they have a strong site preference, both seasonally and inter-annually. Site fidelity was also the highest at the GG. In sharks with deployment times longer than 300 days, we found that > 80% of visits of all mature males were at GG, 80% of visits of a single mature female occurred there, > 85% of visits of most juvenile males, and > 70% of visits of most juvenile females. At GG, sharks moved into the range of the receiver day and night without a strong preference for a particular time of the day, which implies movements up and down the area day and night. At most other locations within the bay, sharks were present during daytime hours, while at Point Reyes during nighttime hours. Sharks moved into SFB during early spring and summer, and moved out of SFB to Point Reyes during late spring and fall. Three sevengill sharks migrated roughly 800 km southeastward along the coastline from SFO, one making three trips back and forth between the sites. Conclusions There was strong evidence of residency of sharks within SFB, and sharks repeatedly returned to the same region of the bay with some sharks making long-distance movements

Electronic supplementary information from Odours from marine plastic debris induce food search behaviours in a forage fish

Plastic pollution is an anthropogenic stressor in marine ecosystems globally. Many species of marine fish (more than 50) ingest plastic debris. Ingested plastic has a variety of lethal and sublethal impacts and can be a route for bioaccumulation of toxic compounds throughout the food web. Despite its pervasiveness and severity, our mechanistic understanding of this maladaptive foraging behaviour is incomplete. Recent evidence suggests that the chemical signature of plastic debris may explain why certain species are predisposed to mistaking plastic for food. Anchovy (<i>Engraulis</i> sp.) are abundant forage fish in coastal upwelling systems and a critical prey resource for top predators. Anchovy ingest plastic in natural conditions, though the mechanism they use to misidentify plastic as prey is unknown. Here, we presented wild-caught schools of Northern Anchovy (<i>Engraulis mordax</i>) with odour solutions made of plastic debris and clean plastic to compare school-wide aggregation and rheotactic responses relative to food and food odour presentations. Anchovy schools responded to plastic debris odour with increased aggregation and reduced rheotaxis. These results were similar to the effects food and food odour presentations had on schools. Conversely, these behavioural responses were absent in clean plastic and control treatments. To our knowledge, this is the first experimental evidence that adult anchovy use odours to forage. We conclude that the chemical signature plastic debris acquires in the photic zone can induce foraging behaviours in anchovy schools. These findings provide further support for a chemosensory mechanism underlying plastic consumption by marine wildlife. Given the trophic position of forage fish, these findings have considerable implications for aquatic food webs and possibly human health

Figure S2: Example black and white images for clustering analysis from Odours from marine plastic debris induce food search behaviours in a forage fish

Example of still images from figure S1 transferred to black and white using ImageJ for aggregation analysis. A) control (dyed seawater) treatment B) food C) clean plastic treatment, “high” concentration D) biofouled plastic odor treatment, “high” concentration E) food odor treatment, “high” concentration

Figure S1: Example images for clustering analysis from Odours from marine plastic debris induce food search behaviours in a forage fish

Examples of still images taken from videos of a Northern Anchovy (E. mordax) school 30 and 60 seconds after treatment introduction illustrating the differences in behavioural response by treatment A) control (dyed seawater) treatment B) food treatment C) clean plastic treatment, “high” concentration D) biofouled plastic odor treatment, “high” concentration E) food odor treatment, “high” concentration

Figure S1 from Odours from marine plastic debris induce food search behaviours in a forage fish

Examples of still images taken from videos of a northern anchovy (E. mordax) school 30 and 60 seconds after treatment introduction illustrating the differences in behavioural response by treatment A) control (dyed seawater) treatment B) food treatment C) clean plastic treatment, “high” concentration D) biofouled plastic odor treatment, “high” concentration E) food odor treatment, “high” concentration

Figure S2 from Odours from marine plastic debris induce food search behaviours in a forage fish

Example of still images from figure S1 transferred to black and white using ImageJ for aggregation analysis. A) control (dyed seawater) treatment B) food C) clean plastic treatment, “high” concentration D) biofouled plastic odor treatment, “high” concentration E) food odor treatment, “high” concentration

Multicenter US Clinical Trial With an Electric-Acoustic Stimulation (EAS) System in Adults: Final Outcomes.

OBJECTIVE: To demonstrate the safety and effectiveness of the MED-EL Electric-Acoustic Stimulation (EAS) System, for adults with residual low-frequency hearing and severe-to-profound hearing loss in the mid to high frequencies. STUDY DESIGN: Prospective, repeated measures. SETTING: Multicenter, hospital. PATIENTS: Seventy-three subjects implanted with PULSAR or SONATA cochlear implants with FLEX electrode arrays. INTERVENTION: Subjects were fit postoperatively with an audio processor, combining electric stimulation and acoustic amplification. MAIN OUTCOME MEASURES: Unaided thresholds were measured preoperatively and at 3, 6, and 12 months postactivation. Speech perception was assessed at these intervals using City University of New York sentences in noise and consonant-nucleus-consonant words in quiet. Subjective benefit was assessed at these intervals via the Abbreviated Profile of Hearing Aid Benefit and Hearing Device Satisfaction Scale questionnaires. RESULTS: Sixty-seven of 73 subjects (92%) completed outcome measures for all study intervals. Of those 67 subjects, 79% experienced less than a 30 dB HL low-frequency pure-tone average (250-1000 Hz) shift, and 97% were able to use the acoustic unit at 12 months postactivation. In the EAS condition, 94% of subjects performed similarly to or better than their preoperative performance on City University of New York sentences in noise at 12 months postactivation, with 85% demonstrating improvement. Ninety-seven percent of subjects performed similarly or better on consonant-nucleus-consonant words in quiet, with 84% demonstrating improvement. CONCLUSION: The MED-EL EAS System is a safe and effective treatment option for adults with normal hearing to moderate sensorineural hearing loss in the low frequencies and severe-to-profound sensorineural hearing loss in the high frequencies who do not benefit from traditional amplification