What is a biobank? Differing definitions among biobank stakeholders

While there is widespread agreement on the broad aspects of what constitutes a biobank, there is much disagreement regarding the precise definition. This research aimed to describe and analyze the definitions of the term biobank offered by various stakeholders in biobanking. Interviews were conducted with 36 biobanking stakeholders with international experience currently working in Switzerland. The results show that, in addition to the core concepts of biological samples and linked data, the planned use of samples (including sharing) is held to be a key criterion. It also emerges that some researchers avoid the term in order to circumvent certain regulatory guidelines, including informed consent requirements. Developments in the field of biobanking will be complicated if researchers are unaware, or deny that their collection is a biobank. A clear definition of the term is therefore an important step towards fostering collaboration amongst researchers, enabling them to more easily identify potential sources of samples.     

‘Chronophilia’: Entries of Erotic Age Preference into Descriptive Psychopathology

A scientific nomenclature of erotic age preferences informed the mid- through late nineteenth century joint appearance of homosexuality and sexual abuse of minors on the medico-legal scene. Yet, even in the twenty-first century, legal, psychiatric and culture-critical dimensions of related terms are rarely cleanly distinguished. Review of primary sources shows the ongoing Western suspension of notions of ‘sick desire’, alongside and beyond the medicalisation of homosexuality, between metaphor, legal interdiction and postulated psychopathology. Virtually all early attention to erotic age preference occurred in the context of emergent attention to erotic gender preference. Age of attraction and age difference centrally animate modern homosexuality’s pre-modern past; its earliest psychiatric nomenclature and typologies (1844–69); its early aetiologies stipulating degrees of sexual differentiation (1890s); its concomitant sub-classification (1896–1914); its earliest psychophysiological tests (1950s); and, finally, its post-psychiatric, social scientific typologies (1980s). Several identifications of ‘paedophilia’ were seen throughout the 1890s but as a trope it gained cultural momentum only during, and as a seemingly intriguing corollary of, the progressive depsychiatricisation of homosexuality across the Anglo-European world (late 1950s through 1980s). Early twentieth century sources varied in having it denote (1) a distinct perversion, thus possible ‘complication’ of sexual inversion (2) a discrete corollary of psychosexual differentiation akin to gender preference (3) a distinct subtype of fetishism, thus a likely imprint of early seduction (4) a more intricate expression of erotic symbolism or psychosexual complex or (5) a taste answering to culture, a lack of it, or a libertine disregard for it.     

Demographic and prosocial intrapersonal characteristics of biobank participants and refusers: the findings of a survey in the Netherlands

Research in genetics relies heavily on voluntary contributions of personal data. We aimed to acquire insights into the differences between participants and refusers of participation in a Dutch population-based biobank. Accordingly, we assessed the demographic and prosocial intrapersonal characteristics of respondents who participated (n = 2615) or refused to participate (n = 404) in the Lifelines biobank and databank. Our results indicated that health-related values critically influence participation decisions. The participation threshold for Lifelines was determined by an absence of health-related values and of trust in government. Therefore, considering these factors in communication and recruitment strategies could enhance participation in biomedical research. No indications were found of a stronger general prosociality of participants or their trust in researchers beyond the context of biobanking. This emphasizes the contextual understanding of the decision of participation in biobanking. Our findings may contribute to improving recruitment strategies by incorporating relevant values and/or highlighting prosocial benefits. Moreover, they foreground the need to address trust issues in collaborations between data repositories and commercial companies. Future research should explore how prosocial intrapersonal characteristics drive participation and withdrawal decisions and relate to contextual attributes.Subject terms: Genetics research, Epidemiology     

Colocalization analysis of polycystic ovary syndrome to identify potential disease-mediating genes and proteins

Polycystic ovary syndrome (PCOS) is a common complex disease in women with a strong genetic component and downstream consequences for reproductive, metabolic and psychological health. There are currently 19 known PCOS risk loci, primarily identified in women of Han Chinese or European ancestry, and 14 of these risk loci were identified or replicated in a genome-wide association study of PCOS performed in up to 10,074 cases and 103,164 controls of European descent. However, for most of these loci the gene responsible for the association is unknown. We therefore use a Bayesian colocalization approach (Coloc) to highlight genes in PCOS-associated regions that may have a role in mediating the disease risk. We evaluated the posterior probabilities of evidence consistent with shared causal variants between 14 PCOS genetic risk loci and intermediate cellular phenotypes in one protein (N = 3301) and two expression quantitative trait locus datasets (N = 31,684 and N = 80–491). Through these analyses, we identified seven proteins or genes with evidence of a possibly shared causal variant for almost 30% of known PCOS signals, including follicle stimulating hormone and ERBB3, IKZF4, RPS26, SUOX, ZFP36L2, and C8orf49. Several of these potential effector proteins and genes have been implicated in the hypothalamic–pituitary–gonadal signalling pathway and provide an avenue for functional follow-up in order to demonstrate a causal role in PCOS pathophysiology.Subject terms: Endocrine reproductive disorders, Quantitative trait     

The New AASM Criteria for Scoring Hypopneas: Impact on the Apnea Hypopnea Index

Study Objectives:

To compare apnea-hypopnea indices (AHIs) derived using 3 standard hypopnea definitions published by the American Academy of Sleep Medicine (AASM); and to examine the impact of hypopnea definition differences on the measured prevalence of obstructive sleep apnea (OSA).

Design:

Retrospective review of previously scored in-laboratory polysomnography (PSG).

Setting:

Two tertiary-hospital clinical sleep laboratories.

Patients or Participants:

328 consecutive patients investigated for OSA during a 3-month period.

Interventions:

N/A

Measurements and Results:

AHIs were originally calculated using previous AASM hypopnea scoring criteria (AHI_Chicago), requiring either > 50% airflow reduction or a lesser airflow reduction with associated > 3% oxygen desaturation or arousal. AHIs using the “recommended” (AHI_Rec) and the “alternative” (AHI_Alt) hypopnea definitions of the AASM Manual for Scoring of Sleep and Associated Events were then derived in separate passes of the previously scored data. In this process, hypopneas that did not satisfy the stricter hypopnea definition criteria were removed. For AHI_Rec, hypopneas were required to have ≥ 30% airflow reduction and ≥ 4% desaturation; and for AHI_Alt, hypopneas were required to have ≥ 50% airflow reduction and ≥ 3% desaturation or arousal. The median AHI_Rec was approximately 30% of the median AHI_Chicago, whereas the median AHI_Alt was approximately 60% of the AHI_Chicago, with large, AHI-dependent, patient-specific differences observed. Equivalent cut-points for AHI_Rec and AHI_Alt compared to AHI_Chicago cut-points of 5, 15, and 30/h were established with receiver operator curves (ROC). These cut-points were also approximately 30% of AHI_Chicago using AHI_Rec and 60% of AHI_Chicago using AHI_Alt. Failure to adjust cut-points for the new criteria would result in approximately 40% of patients previously classified as positive for OSA using AHI_Chicago being negative using AHI_Rec and 25% being negative using AHI_Alt.

Conclusions:

This study demonstrates that using different published standard hypopnea definitions leads to marked differences in AHI. These results provide insight to clinicians and researchers in interpreting results obtained using different published standard hypopnea definitions, and they suggest that consideration should be given to revising the current scoring recommendations to include a single standardized hypopnea definition.

Citation:

Ruehland WR; Rochford PD; O''Donoghue FJ; Pierce RJ; Singh P; Thornton AT. The new AASM criteria for scoring hypopneas: Impact on the apnea hypopnea index. SLEEP 2009;32(2):150–157.     

New chaps in the histone chaperone arena

Understanding exactly how chromatin is assembled is paramount to addressing how select histone modifications may be transmitted, a putative epigenetic process. In the June 15, 2010, issue of Genes & Development, Drané and colleagues (pp. 1253–1265) identified DAXX as a novel H3.3-specific chaperone. This finding, in the context of others published by Goldberg and colleauges in Cell and Sawatsubashi and colleagues (pp. 159–170) in the January 15, 2010, issue of Genes & Development, provides the impetus for uncovering the mechanistic and functional properties of alternative histone deposition pathways.     

Differences in metabolic parameters and cardiovascular risk between American Diabetes Association and World Health Organization definition of impaired fasting glucose in European Caucasian subjects: a cross-sectional study

Introduction

The American Diabetes Association (ADA) defines impaired fasting glucose (IFG) as fasting plasma glucose concentration of 100–125 mg/dl, whereas the World Health Organization (WHO) and the International Diabetes Federation (IDF) define IFG as fasting plasma glucose levels of 110–125 mg/dl. We identified differences in metabolic parameters and cardiovascular disease (CVD) risk according to the ADA or WHO/IDF definition of IFG.

Material and methods

Healthy drug-naive Caucasian (Greek) subjects (n = 396; age 55 ±12 years) participated in this cross-sectional study.

Results

Diastolic blood pressure (DBP) and uric acid levels were higher in the subjects with glucose 100–109 mg/dl compared with those with glucose < 100 mg/dl (87 ±9 mm Hg vs. 84 ±11 mm Hg, p = 0.004 for DBP, 5.6 ±1.5 mg/dl vs. 5.0 ±1.0 mg/dl, p = 0.002 for uric acid), whereas triglyceride levels were lower in subjects with glucose 100–109 mg/dl compared with those with glucose ≥ 110 mg/dl (169 mg/dl (interquartile range (IQR) = 102–186) vs. 186 mg/dl (IQR = 115–242), p = 0.002). Only the ADA definition recognized subjects with significantly increased 10-year CVD risk estimation (SCORE risk calculation) compared with their respective controls (5.4% (IQR = 0.9–7.3) vs. 4.1% (IQR = 0.7–5.8), p = 0.002).

Conclusions

The ADA IFG definition recognized more subjects with significantly increased CVD risk (SCORE model) compared with the WHO/IDF definition.     

Predictive factors of proximal advanced neoplasia in the large bowel

Introduction

The aim of the study was to evaluate the impact of sex, age, family history and distal findings on the risk of proximal advanced neoplasia (cancer or advanced adenoma) in the large bowel.

Material and methods

Records for 10 111 asymptomatic participants of the Colonoscopy Screening Program (CSP), recruited from the Warsaw region between 2000 and 2004, were analyzed. A multivariate logistic regression model was used to estimate the impact of sex, age, family history and most advanced distal lesions on the occurrence of proximal advanced neoplasia. To enhance comparability of the study two definitions of the proximal colon were applied – either the splenic flexure (1^st) or the bend between the descending and sigmoid colon (2^nd definition) represented the boundary.

Results

One hundred and thirty-three (1^st) and 167 patients (2^nd definition) were found to have at least one advanced neoplastic lesion in the proximal part, respectively. Eleven and 14 patients were found to have carcinoma, while in 130 and 163 patients at least one proximal advanced adenoma appeared. Men were at twice as high risk of having advanced neoplasia in the proximal colon than women (OR = 1.94, 95% CI: 1.31–2.87, p = 0.001 or OR = 1.69, 95% CI: 1.20–2.40, p = 0.003, respectively). The presence of distal advanced neoplastic lesions was associated with 3.5 times higher risk of proximal advanced neoplasia (OR = 3.58, 95% CI: 2.00–6.43, p < 0.0001 or OR = 3.41, 95% CI: 1.95–5.96, p < 0.0001), respectively.

Conclusions

The results may confirm some limitation of flexible sigmoidoscopy in the screening settings in comparison with colonoscopy, at least in men and people with distal advanced neoplasia.     

A meta-analysis on the efficacy and tolerability of natalizumab in relapsing multiple sclerosis

Introduction

Natalizumab is a new humanized monoclonal antibody used in multiple sclerosis (MS). The aim of this meta-analysis was to evaluate the efficacy and tolerability of this drug in relapsing MS. PubMed, Scopus, Web of Science, and Cochrane Central Register of Controlled Trials were searched for studies that investigated the efficacy and/or tolerability of natalizumab in MS. Data were collected from 1966 to 2008 (up to October).

Material and methods

The search terms were: “multiple sclerosis” or “MS” and “natalizumab”. “Mean change in Expanded Disability Status Scale (EDSS)”, “number of patients with at least one relapse”, and “number of patients with at least one new gadolinium (Gd)-enhancing lesion” were the key outcomes of interest for assessment of efficacy. “Any adverse events”, “serious adverse events”, “death”, and “withdrawal because of adverse events” were the key outcomes for tolerability. Among existing trials, four randomized placebo controlled clinical trials met our criteria and were included.

Results

Pooled relative risk for at least one relapse in four trials including all doses was 0.7, with a non-significant RR (95% CI: 0.42–1.17, p = 0. 17). Summary RR for at least one relapse in two trials in which doses of 3 mg/kg or 6 mg/kg or 300 mg every 4 weeks were administered gave a value of 0.5 asa significant RR (95% CI: 0.42–0.61, p < 0.0001). The summary RR for at least one new Gd-enhancing lesion was 0.22, a non-significant RR (95% CI: 0.05–1.01, p = 0.051). Three deaths were reported in the natalizumab group. Comparing adverse events between natalizumab and placebo yielded a non-significant RR of 0.99 (95% CI: 0.96–1.01, p = 0.34) for any adverse events (n = 3), and a significant RR of 0.39 (95% CI: 0.29–0.52, p < 0.0001) for serious adverse events (n = 2). The summary RR for withdrawal due to adverse events by natalizumab vs. placebo therapy between two trials was 1.43, a non-significant RR (95% CI: 0.68–3.02, p = 0.35).

Conclusions

It seems that using 3 or 6 mg/kg every 4 weeks is the best method of administration of natalizumab for preventing relapse and occurrence of new Gd-enhancing lesions. The current data on the efficacy and safety of natalizumab are insufficient to reach a convincing conclusion and thus further clinical trials are still needed.     

Intratumoral Patterns of Genomic Imbalance in Glioblastomas

Glioblastomas are morphologically and genetically heterogeneous, but little is known about the regional patterns of genomic imbalance within glioblastomas. We recently established a reliable whole genome amplification (WGA) method to randomly amplify DNA from paraffin‐embedded histological sections with minimum amplification bias [Huang et al (J Mol Diagn 11: 109–116, 2009)]. In this study, chromosomal imbalance was assessed by array comparative genomic hybridization (CGH; Agilent 105K, Agilent Technologies, Santa Clara, CA, USA), using WGA‐DNA from two to five separate tumor areas of 14 primary glioblastomas (total, 41 tumor areas). Chromosomal imbalances significantly differed among glioblastomas; the only alterations that were observed in ≥6 cases were loss of chromosome 10q, gain at 7p and loss of 10p. Genetic alterations common to all areas analyzed within a single tumor included gains at 1q32.1 (PIK3C2B, MDM4), 4q11–q12 (KIT, PDGFRA), 7p12.1–11.2 (EGFR), 12q13.3–12q14.1 (GLI1, CDK4) and 12q15 (MDM2), and loss at 9p21.1–24.3 (p16^INK4a/p14^ARF), 10p15.3–q26.3 (PTEN, etc.) and 13q12.11–q34 (SPRY2, RB1). These are likely to be causative in the pathogenesis of glioblastomas (driver mutations). In addition, there were numerous tumor area‐specific genomic imbalances, which may be either nonfunctional (passenger mutations) or functional, but constitute secondary events reflecting progressive genomic instability, a hallmark of glioblastomas.     

Operational Definition Identifying Osteoporotic Vertebral Fractures in the Claims Database

BackgroundWe analyzed the International Classification of Diseases, 10th edition (ICD-10) diagnostic codes, procedure codes, and radiographic image codes for vertebral fracture (VF) used in the database of Health Insurance Review and Assessment Service (HIRA) of Korea to establish a validated operational definition for identifying patients with osteoporotic VF in claims data.MethodsWe developed three operational definitions for detecting VFs using 9 diagnostic codes, 5 procedure codes and 4 imaging codes. Medical records and radiographs of 2,819 patients, who had primary and subordinated codes of VF between January 2016 and December 2016 at two institutions, were reviewed to detect true vertebral fractures. We evaluated the sensitivity and positive predictive value (PPV) of the operational definition in detecting true osteoporotic VF and obtained the receiver operating characteristic (ROC) curve.ResultsAmong the 2,819 patients who had primary or secondary diagnosis codes for VF, 995 patients satisfied at least one of the criteria for the operational definition of osteoporotic VF. Of these patients, 594 were judged as having true fractures based on medical records and radiographic examinations. The sensitivity and PPV were 62.5 (95% confidence interval [CI], 59.4–65.6) and 59.7(95% CI, 56.6–62.8) respectively. In the receiver operating characteristic analysis, area under the curve (AUC) was 0.706 (95% CI, 0.688–0.724).ConclusionOur findings demonstrate the validity of our operational definitions to identify VFs more accurately using claims data. This algorithm to identify VF is likely to be useful in future studies for diagnosing osteoporotic VF.     

30 year experience of index case identification and outcomes of cascade testing in high-risk breast and colorectal cancer predisposition genes

It is 30 years since the first diagnostic cancer predisposition gene (CPG) test in the Manchester Centre for Genomic Medicine (MCGM), providing opportunities for cancer prevention, early detection and targeted treatments in index cases and at-risk family members. Here, we present time trends (1990–2020) of identification of index cases with a germline CPG variant and numbers of subsequent cascade tests, for 15 high-risk breast and gastro-intestinal tract cancer-associated CPGs: BRCA1, BRCA2, PALB2, PTEN, TP53, APC, BMPR1a, CDH1, MLH1, MSH2, MSH6, PMS2, SMAD4, STK11 and MUTYH. We recorded 2082 positive index case diagnostic screening tests, generating 3216 positive and 3140 negative family cascade (non-index) tests. This is equivalent to an average of 3.05 subsequent cascade tests per positive diagnostic index test, with 1.54 positive and 1.51 negative non-index tests per family. The CPGs with the highest numbers of non-index positive cases identified on cascade testing were BRCA1/2 (n = 1999) and the mismatch repair CPGs associated with Lynch Syndrome (n = 731). These data are important for service provision and health economic assessment of CPG diagnostic testing, in terms of cancer prevention and early detection strategies, and identifying those likely to benefit from targeted treatment strategies.Subject terms: Cancer genetics, Genetics research     

Near-Road Exposure and Impact of Air Pollution on Allergic Diseases in Elementary School Children: A Cross-Sectional Study

PurposeThe study aims to classify schools based on traffic pollutants and their complex sources, to assess the environment, to determine the state of allergic diseases among students using the International Study of Asthma and Allergies in children (ISAAC) questionnaire, and to assess their connection to air pollutants.ResultsThe frequency of asthma treatment during the past 12 months showed a significant increase (p<0.05) with exposure to NO₂ [1.67, 95% confidence intervals (CIs) 1.03–2.71] in the complex source zones. The frequency of allergic rhinitis treatment during the past 12 months increased significantly with exposure to Black Carbon (1.60, 95% CIs 1.36–1.90) (p<0.001), SO₂ (1.09, 95% CIs 1.01–1.17) (p<0.05), NO₂ (1.18, 95% CIs 1.07–1.30) (p<0.01) for all subjects.ConclusionIn terms of supporting children''s health, care, and prevention related to major spaces for children, such as school zones, spaces used in coming to and leaving school, playgrounds, and classrooms are essential to ensuring not only the safety of children from traffic accidents but also their protection from local traffic pollutants and various hazardous environmental factors.     

Identifying the nature and extent of public and donor concern about the commercialisation of biobanks for genomic research

Various forms of private investment are considered necessary for the sustainability of biobanks, yet pose significant challenges to public trust. To manage this tension, it is vital to identify the concerns of relevant stakeholders to ensure effective and acceptable policy and practice. This research examines the aspects of commercialisation that are of most concern to the Australian public (n = 800) and patients who had donated their tissue to two large disease specific (cancer) public biobanks (n = 564). Overall, we found a commercialisation effect (higher support for public relative to private) in relation to funding, research location and access to stored biospecimens. The effect was strongest for research locations and access compared to funding. A latent class analysis revealed the pattern of concern differed, with the majority (34.1%) opposing all aspects of commercialisation, a minority supporting all (15.7%), one quarter (26.8%) opposing some (sharing and selling tissue) but not others (research locations and funding), and a group who were unsure about most aspects but opposed selling tissue (23.5%). Patient donors were found to be more accepting of and unsure about most aspects of commercialisation. Members of the (general) public who were motivated to participate in biobanking were more likely to oppose some aspects while supporting others, while those who indicated they would not donate to a biobank were more likely to oppose all aspects of commercialisation. The results suggest that approaches to policy, engagement and awareness raising need to be tailored for different publics and patient groups to increase participation.Subject terms: Genetics research, Ethics     

Anti-Inflammatory and Antioxidant Effects of an Ethanolic Extract of the Aerial Parts of Hilleria Latifolia (Lam.) H. Walt. (Phytolaccaceae)

Various parts of the perennial herb Hilleria latifolia (Lam.) H. Walt. (Family: Phytolaccaceae) are used in Ghanaian traditional medicine for the treatment of several inflammatory-related disorders. The present study examined the anti-inflammatory effect of an ethanolic extract of the aerial parts of Hilleria latifolia (HLE) in acute and chronic inflammation models. Since free radicals and reactive oxygen species are implicated in inflammatory diseases, the antioxidant potential of HLE was also investigated in in vitro experimental models. HLE (10–300 mg kg⁻¹, p.o.), either preemptively or curatively, significantly inhibited carrageenan-induced foot oedema in 7-day old chicks. Similarly, the NSAID diclofenac (10–100 mg kg⁻¹, i.p.) and the steroidal anti-inflammatory agent dexamethasone (0.3–3 mg kg⁻¹, i.p.) dose-dependently reduced the oedema in both pre-emptive and curative treatments. In the Freund''s adjuvant induced-arthritis model in rats, HLE as well as the positive controls, dexamethasone and methotrexate, showed significant anti-arthritic properties when applied to established adjuvant arthritis. HLE (10–300 mg kg⁻¹, p.o.) significantly reduced oedema in the ipsilateral paw of rats but failed to prevent systemic arthritic spread. The DMARD methotrexate (0.1–1 mg kg⁻¹, i.p.) and dexamethasone (0.3–3 mg kg⁻¹, i.p.) reduced significantly the total polyarthritic oedema as well as the spread of the arthritis from the ipsilateral to the contralateral paws of the treated animals. The extract (0.03–1.00 mg ml⁻¹) exhibited Fe³⁺ reducing activity, scavenged DPPH and prevented lipid peroxidation. These findings suggest that the extract exerts in vivo anti-inflammatory activity after oral administration and also has antioxidant properties which may contribute to its activity.     

Blunted rest–activity rhythms link to higher body mass index and inflammatory markers in children

Study ObjectivesDisturbances of rest–activity rhythms are associated with higher body mass index (BMI) in adults. Whether such relationship exists in children is unclear. We aimed to examine cross-sectional associations of rest–activity rhythm characteristics with BMI z-score and obesity-related inflammatory markers in school-age children.MethodsParticipants included 411 healthy children (mean ± SD age 10.1 ± 1.3 years, 50.8% girls) from a Mediterranean area of Spain who wore wrist accelerometers for 7 consecutive days. Metrics of rest–activity rhythm were derived using both parametric and nonparametric approaches. Obesity-related inflammatory markers were measured in saliva (n = 121).ResultsIn a multivariable-adjusted model, higher BMI z-score is associated with less robust 24-h rest–activity rhythms as represented by lower relative amplitude (–0.16 [95% CI –0.29, –0.02] per SD, p = 0.02). The association between BMI z-score and relative amplitude persisted with additional adjustment for sleep duration, and attenuated after adjustment for daytime activity level. Less robust rest–activity rhythms were related to increased levels of several salivary pro-inflammatory markers, including C-reactive protein, which is inversely associated with relative amplitude (–32.6% [–47.8%, –12.9%] per SD), independently of BMI z-score, sleep duration, and daytime activity level.ConclusionBlunted rest–activity rhythms are associated with higher BMI z-score and salivary pro-inflammatory markers already at an early age. The association with BMI z-score seem to be independent of sleep duration, and those with pro-inflammatory markers further independent of BMI z-score and daytime activity. Novel intervention targets at an early age based on improving the strength of rest–activity rhythms may help to prevent childhood obesity and related inflammation.Clinical Trials Registration{"type":"clinical-trial","attrs":{"text":"NCT02895282","term_id":"NCT02895282"}}NCT02895282     

In vivo measurement of fascicle length and pennation of the human anconeus muscle at several elbow joint angles

Ultrasound imaging has facilitated the reliable measure of the architectural variables fascicle length (L_F) and pennation angle (PA), at rest and during static and dynamic contractions in many human skeletal muscles in vivo. Despite its small size and very modest contribution to elbow extension torque, the anconeus muscle has proven a useful model for the study of neuromuscular function in health and disease. Recent single motor unit (MU) studies in the anconeus have reported discrete and identifiable individual trains of MU potentials from intramuscular electromyography (EMG) recordings during dynamic elbow extensions. It is unknown whether the anconeus has unique architectural features related to alterations in L_F and PA throughout the elbow joint range of motion that may help explain these high-quality recordings. Previous anatomical studies have investigated this muscle in cadavers and at mainly one elbow joint angle. The purpose of this study was to measure in vivo PA and L_F of the anconeus muscle in a relaxed state at different degrees of elbow flexion using ultrasonography. Ultrasound images were collected from 10 healthy males (25 ± 3 years) at 135°, 120°, 90°, 45°, and 0° of elbow flexion. Average values of L_F decreased by 6 mm (10%), 6 mm (12%), and 4 mm (9%) from 135–120°, 120–90°, and 90–45° of elbow flexion, respectively, whereas average PA values increased by 1° (9%), 1° (8%), and 2° (14%) from 135–120°, 120–90°, and 45–0°, respectively. The results indicate that anconeus muscle architecture is dynamic, undergoing moderate changes with elbow joint excursion that are similar to other limb muscles reported elsewhere. The data obtained here are more comprehensive and representative of architectural changes at various elbow joint positions than those data reported in cadaveric studies. Furthermore, the results of this study indicate that despite experiencing similar relative changes in muscle architecture to other skeletal muscles about the elbow joint, the minimal absolute changes in L_F of the anconeus likely contribute to the clarity of intramuscular EMG previously reported in this muscle.     

A 3-Mb Contig from D11S987 to MLK3, a Gene-Rich Region in 11q13

We have combined genetic, radiation-reduced somatic cell hybrid (RRH), fluorescent in situ hybridization (FISH), and physical mapping methods to generate a contig of overlapping YAC, PAC, and cosmid clones corresponding to >3 continuous Mb in 11q13. A total of 15 STSs [7 genes (GSTP1, ACTN, PC, MLK3, FRA1, SEA, HNP36), 4 polymorphic loci (D11S807, D11S987, GSTP1, D11S913), 3 ESTs (D11S1956E, D11S951E, and WI-12191), and 1 anonymous STS (D11S703)], mapping to three independent RRH segregation groups, identified 26 YAC, 7 PAC, and 16 cosmid clones from the CGM, Roswell Park, CEPH Mark I, and CEPH MegaYAC YAC libraries, a 5 genome equivalent PAC library, and a chromosome 11-specific cosmid library. Thirty-six Alu–PCR products derived from 10 anonymous bacteriophage λ clones, a cosmid containing the polymorphic marker D11S460, or STS-positive YAC or cosmid clones were identified and used to screen selected libraries by hybridization, resulting in the identification of 19 additional clones. The integrity and relative position of a subset of clones was confirmed by FISH and were found to be consistent with the physical and RRH mapping results. The combination of STS and Alu–PCR-based approaches has proven to be successful in attaining contiguous cloned coverage in this very GC-rich region, thereby establishing for the first time the absolute order and distance between the markers: CEN–MLK3–(D11S1956E/D11S951E/WI-12191)–FRA1–D11S460–SEA–HNP36/D11S913–ACTN–PCD11S703–GSTP1–D11S987–TEL.