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© 2019 The Authors. We study the dynamics of specialness for 1‐day repo contracts on Italian government bonds over a 10‐year sample period. As predicted by Duffie's (1996) model, our results show that collateral supply is a significant factor for specialness. However, we enrich that finding by also showing a clear impact from repo liquidity, collateral riskiness, information uncertainty, and short‐selling proxies, revealing the importance of speculative bond demand for specialness. During crisis periods, bond fire sales and European Central Bank interventions also have a large impact on repo specialness. We identify recurrent patterns for specialness around bond auctions. Specialness increases steadily from the auction announcement date until a few days before the auction settlement date, which is consistent with overbidding behaviour and a short selling of treasuries (via reverse repos) from primary dealers ahead of auctions.

We examine whether performance persistence is suspicious. Top quintile portfolios formed on the Sharpe ratio, alpha, and information ratio persistently outperform similarly constructed mediocre third quintile portfolios throughout our sample period, but performance is more modest and less persistent when portfolios are formed on the excess manipulation-proof performance measure (EMPPM). By selecting funds formed on ranking by Sharpe and information ratios, investors also select funds that have persistently doubtful performance according to the doubt ratio. In contrast, portfolios formed on alphas and especially the EMPPM have much less excess and persistent doubt.

Histone deacetylase (HDAC) inhibitors are an emerging class of potential antimalarial drugs. We investigated the antiplasmodial properties of 16 alkoxyurea-based HDAC inhibitors containing various cap and zinc binding groups (ZBGs). Ten compounds displayed sub-micromolar activity against the 3D7 line of Plasmodium falciparum. Structure-activity relationship studies revealed that a hydroxamic acid ZBG is crucial for antiplasmodial activity, and that the introduction of bulky alkyl substituents to cap groups increases potency against asexual blood-stage parasites. We also demonstrate that selected compounds cause hyperacetylation of P. falciparum histone H4, indicating inhibition of one or more PfHDACs. To assess the selectivity of alkoxyurea-based HDAC inhibitors for parasite over normal mammalian cells, the cytotoxicity of representative compounds was evaluated against neonatal foreskin fibroblast (NFF) cells. The most active compound, 6-((3-(4-(tert-butyl)phenyl)ureido)oxy)-N-hydroxyhexanamide (1 e, Pf3D7 IC50 : 0.16 μM) was 31-fold more toxic against the asexual blood stages than towards normal mammalian cells. Moreover, a subset of four structurally diverse HDAC inhibitors revealed moderate activity against late-stage (IV-V) gametocytes.

Objective The purpose of this study was to examine how well two commonly used age-based prediction equations for maximal heart rate (HRmax) estimate the actual HRmax measured in Black and White adults from the HERITAGE Family Study. Methods A total of 762 sedentary subjects (39% Black, 57% Females) from HERITAGE were included. HRmax was measured during maximal exercise tests using cycle ergometers. Age-based HRmax was predicted using the Fox (220-age) and Tanaka (208 – 0.7 × age) formulas. Results The standard error of estimate (SEE) of predicted HRmax was 12.4 and 11.4 bpm for the Fox and Tanaka formulas, respectively, indicating a wide-spread of measured-HRmax values are compared to their age-predicted values. The SEE (shown as Fox/Tanaka) was higher in Blacks (14.4/13.1 bpm) and Males (12.6/11.7 bpm) compared to Whites (11.0/10.2 bpm) and Females (12.3/11.2 bpm) for both formulas. The SEE was higher in subjects above the BMI median (12.8/11.9 bpm) and below the fitness median (13.4/12.4 bpm) when compared to those below the BMI median (12.2/11.0 bpm) and above the fitness median (11.4/10.3) for both formulas. Conclusion Our findings show that based on the SEE, the prevailing age-based estimated HRmax equations do not precisely predict an individual's measured-HRmax. Am. J. Hum. Biol., 25:695–701, 2013. © 2013 Wiley Periodicals, Inc.

Recent advances in top-down mass spectrometry using native electrospray now enable the analysis of intact protein complexes with relatively small sample amounts in an untargeted mode. Here, we describe how to characterize both homo- and heteropolymeric complexes with high molecular specificity using input data produced by tandem mass spectrometry of whole protein assemblies. The tool described is a “search engine for multi-proteoform complexes,” (SEMPC) and is freely-available at http://complexsearch.kelleher.northwestern.edu. The output is a list of candidate multi-proteoform complexes and scoring metrics, which are used to define a distinct set of one or more unique protein subunits, their overall stoichiometry in the intact complex and their pre- and post-translational modifications. Thus, we present an approach for the identification and characterization of intact protein complexes from native mass spectrometry data.

Maselli RA, Arredondo J, Cagney O, Mozaffar T, Skinner S, Yousif S, Davis RR, Gregg JP, Sivak M, Konia TH, Thomas K, Wollmann RL. Congenital myasthenic syndrome associated with epidermolysis bullosa caused by homozygous mutations in PLEC1 and CHRNE. Mutations in the plectin gene (PLEC1) cause epidermolysis bullosa simplex (EBS), which may associate with muscular dystrophy (EBS–MD) or pyloric atresia (EBS–PA). The association of EBS with congenital myasthenic syndrome (CMS) is also suspected to result from PLEC1 mutations. We report here a consanguineous patient with EBS and CMS for whom mutational analysis of PLEC1 revealed a homozygous 36 nucleotide insertion (1506_1507ins36) that results in a reduced expression of PLEC1 mRNA and plectin in the patient muscle. In addition, mutational analysis of CHRNE revealed a homozygous 1293insG, which is a well-known low-expressor receptor mutation. A skin biopsy revealed signs of EBS, and an anconeus muscle biopsy showed signs of a mild myopathy. Endplate studies showed fragmentation of endplates, postsynaptic simplification, and large collections of thread-like mitochondria. Amplitudes of miniature endplate potentials were diminished, but the endplate quantal content was actually increased. The complex phenotype presented here results from mutations in two separate genes. While the skin manifestations are because of the PLEC1 mutation, footprints of mutations in PLEC1 and CHRNE are present at the neuromuscular junction of the patient indicating that abnormalities in both genes contribute to the CMS phenotype.

Objective The aim of the study was to compare the performance of several bedside neuropsychological tools for detection of HIV-associated neurocognitive disorder (HAND) in antiretroviral drug-exposed persons. Methods We analysed the relative performance of the HIV Dementia Scale (HDS), International HIV Dementia Scale (IHDS) and the Mini-Mental Status Exam (MMSE) together with neuropsychological tests (Symbol-Digit, Grooved Pegboard and Trail Making) in HIV-1-seronegative subjects (HIV; n 513) and in HIV-1-seropositive subjects with HAND (HIV 1HAND; n 513) and other neurological disorders (HIV 1OND; n 520). Results Established neuropsychological tests consistently showed significantly poorer performance by HIV 1HAND subjects compared with the other two groups. Similarly, the mean HDS and IHDS scores were lower in the HIV 1HAND group compared with the other two groups (Po0.005) while the mean MMSE score did not show significant differences between the HIV 1HAND and HIV 1OND groups. Receiver operator characteristics curves generated from these data using predefined cut-off scores revealed that the HDS, IHDS and MMSE displayed corresponding area under the curve values of 0.82, 0.74 and 0.48, respectively (Po0.006). Conclusions The present findings indicate that the MMSE is a weak tool for diagnosing HAND in this group of patients but the HDS and IHDS demonstrate better efficiencies, although cut-off values for the HDS require reassessment in the era of effective antiretroviral therapy.

Monitoring is an important aspect of any procedure that seeks to determine whether a technique has worked effectively. The river restoration process is no different. Unfortunately, monitoring is often not undertaken due to constraints on time and resources, as well as the commonly held belief that river restoration is inherently a good thing and, as a result, monitoring is unnecessary. There are many reasons to monitor projects and among the most important is the need to learn from experiences and for regulatory compliance. This paper examines the issues associated with the monitoring of river restoration schemes. In particular, it details monitoring selection models focusing on those associated with ecology and geomorphology. The paper also considers [he requirements of monitoring schemes that will help deliver the goals of the Water Framework Directive (WFD).

Here we seek to spatialise aspects of the Northern Rock Bank crisis of 2007 by marrying two radically different approaches. We combine a discussion of financial lending practices with an articulation of herd behaviour in conditions of uncertainty. Both were part of the still-unfolding picture of a traumatic episode in the geography of finance but also convey lessons on the behaviour of society in situations of shortage.

We studied the effect of ectopic AtCBF over-expression on physiological alterations that occur during cold exposure in frost-sensitive Solanum tuberosum and frost-tolerant Solanum commersonii. Relative to wild-type plants, ectopic AtCBF1 over-expression induced expression of COR genes without a cold stimulus in both species, and imparted a significant freezing tolerance gain in both species: 2 degrees C in S. tuberosum and up to 4 degrees C in S. commersonii. Transgenic S. commersonii displayed improved cold acclimation potential, whereas transgenic S. tuberosum was still incapable of cold acclimation. During cold treatment, leaves of wild-type S. commersonii showed significant thickening resulting from palisade cell lengthening and intercellular space enlargement, whereas those of S. tuberosum did not. Ectopic AtCBF1 activity induced these same leaf alterations in the absence of cold in both species. In transgenic S. commersonii, AtCBF1 activity also mimicked cold treatment by increasing proline and total sugar contents in the absence of cold. Relative to wild type, transgenic S. commersonii leaves were darker green, had higher chlorophyll and lower anthocyanin levels, greater stomatal numbers, and displayed greater photosynthetic capacity, suggesting higher productivity potential. These results suggest an endogenous CBFpathway is involved in many of the structural, biochemical and physiological alterations associated with cold acclimation in these Solanum species.

Summary 1. The cellular nutrient contents of microalgae, when growing at or approaching maximum rates, approximate the Redfield C : N : P (molar) ratio of 106 : 16 : 1. Deviations from this optimal ratio can be used to infer nutrient limitation of microalgal growth. However, this ratio may not be applicable to macroalgae, which are distinguished from microalgae by forming a thallus that is a discrete structure visible to the naked eye. The utility of the Redfield ratio to infer nutrient limitation of the growth of macroalgae was tested for Spirogyra fluviatilis in a field experiment conducted in tropical Australia. 2. The optimal cellular C : N : P ratio for S. fluvialitis was estimated by means of in situ nutrient addition. This was compared with S. fluvialitis cellular ratios determined from eight sites with a wide range of soluble N concentrations (

Scale economies are often touted as the factor behind the trend in the structure of the U.S. hog industry toward fewer and larger hog farms. However, since hog production is multistage and farms either integrate or separate the stages, the appropriate measures are multistage economies. In theory, a smaller and, presumably, high-cost operation, by the standards of single stage/output scale economies, may still be cost-competitive if it enjoys multistage economies — that is if vertical scope economies more than offset stage-specific scale diseconomies. Whether that holds in practice remains heretofore unexplored in the agricultural economics literature. Using a unique data set on hog farms in the U.S. Midwest, we estimate a multistage cost function and provide the first-ever estimates of multistage economies, stage-specific economies, and vertical scope economies in hog production. Les economies d'echelle sont souvent soupconnees d'etre le facteur qui influence la tendance observee dans la structure de l'industrie porcine aux Etats-Unis, soit des porcheries moins nombreuses mais de plus grande taille. Cependant, comme la production porcine est une production a plusieurs stades et que les producteurs peuvent choisir d'integrer ces stades ou d'exploiter un seul stade, les mesures appropriees sont les economies d'echelle liees aux stades multiples. En theorie, une petite porcherie, qui a probablement des couts eleves selon les criteres des economies d'echelle liees a un seul stade, peut tout de meme etre concurrentielle quant aux couts si elle profite des economies d'echelle liees aux stades multiples, c'est-a-dire si les economies de gamme verticales font plus que compenser les deseconomies d'echelle liees a un seul stade. La verification de cette theorie dans la pratique demeure, jusqu'ici, inexploitee dans la litterature agroeconomique. En utilisant un ensemble de donnees sur des porcheries situees dans le Midwest americain, nous avons estime une fonction de cout lie aux stades multiples et nous presentons les premieres estimations d'economies d'echelle liees aux stades multiples, d'economies d'echelle liees a un seul stade et d'economies de gamme verticales dans la production porcine.

Summary Genetic analyses have identified two loci in wheat and barley that mediate the capacity to overwinter in temperate climates. One locus co-segregates with VRN-1, which affects the vernalization requirement. This locus is known as Frost resistance-1 (Fr-1). The second locus, Fr-2, is coincident with a cluster of more than 12 Cbf genes. Cbf homologs in Arabidopsis thaliana play a key regulatory role in cold acclimatization and the acquisition of freezing tolerance. Here we report that the Hordeum vulgare (barley) locus VRN-H1/Fr-H1 affects expression of multiple barley Cbf genes at Fr-H2. RNA blot analyses, conducted on a ‘Nure’בTremois’ barley mapping population segregating for VRN-H1/Fr-H1 and Fr-H2, revealed that transcript levels of all cold-induced Cbf genes at Fr-H2 were significantly higher in recombinants harboring the vrn-H1 winter allele than in recombinants harboring the Vrn-H1 spring allele. Steady-state Cbf2 and Cbf4 levels were also significantly higher in recombinants harboring the Nure allele at Fr-H2. Additional experiments indicated that, in vrn-H1 genotypes requiring vernalization, Cbf expression levels were dampened after plants were vernalized, and dampened Cbf expression was accompanied by robust expression of Vrn-1. Cbf levels were also significantly higher in plants grown under short days than under long days. Experiments in wheat and rye indicated that similar regulatory mechanisms occurred in these plants. These results suggest that VRN-H1/Fr-H1 acts in part to repress or attenuate expression of the Cbf at Fr-H2; and that the greater level of low temperature tolerance attributable to the Nure Fr-H2 allele may be due to the greater accumulation of Cbf2 and Cbf4 transcripts during normal growth and development.

We examine the effect of corporate governance mechanisms on asymmetric information. Using a sample of 392 non-financial UK companies listed in the London Stock Exchange we find that board independence, performance related executive compensation, the number of insiders and leverage are significantly negatively related to asymmetric information whereas the percentage of insider ownership and block ownership are significantly positively related to asymmetric information. The results suggest that UK companies have a high degree of compliance with the combined code on corporate governance and as a result mitigate asymmetric information while contributing towards resolving agency problems.

We examine the relation between credit spreads on industrial bonds and the underlying Treasury term structure. We use zero-coupon spot rates to eliminate the coupon bias and to allow for a consistent study both within and across the different credit ratings. Our results indicate that the level and slope of the Treasury term structure are negatively correlated with changes in the credit spread on investment-grade corporate bonds. We also find that the relation between credit spreads and the Treasury term structure is relatively stable through time. This is good news for value-at-risk calculations, as this suggests that the correlations among assets of different credit classes are stable; therefore use of historic correlations to model spread relations can be valid.

The meristematic tissues of temperate woody perennials must acclimate to freezing temperatures to survive the winter and resume growth the following year. To determine whether the C-repeat binding factor (CBF) family of transcription factors contributing to this process in annual herbaceous species also functions in woody perennials, we investigated the changes in phenotype and transcript profile of transgenic Populus constitutively expressing CBF1 from Arabidopsis (AtCBF1). Ectopic expression of AtCBF1 was sufficient to significantly increase the freezing tolerance of non-acclimated leaves and stems relative to wild-type plants. cDNA microarray experiments identified genes up-regulated by ectopic AtCBF1 expression in Populus, demonstrated a strong conservation of the CBF regulon between Populus and Arabidopsis and identified differences between leaf and stem regulons. We studied the induction kinetics and tissue specificity of four CBF paralogues identified from the Populus balsamifera subsp. trichocarpa genome sequence (PtCBFs). All four PtCBFs are cold-inducible in leaves, but only PtCBF1 and PtCBF3 show significant induction in stems. Our results suggest that the central role played by the CBF family of transcriptional activators in cold acclimation of Arabidopsis has been maintained in Populus. However, the differential expression of the PtCBFs and differing clusters of CBF-responsive genes in annual (leaf) and perennial (stem) tissues suggest that the perennial-driven evolution of winter dormancy may have given rise to specific roles for these 'master-switches' in the different annual and perennial tissues of woody species.

We examine the determinants of the new issue maturity of corporate bonds. As credit rating decreases, new bond issues have longer maturities, but substantial variation in maturity within each rating class remains. We seek to explain the variation of new issue maturity within credit classes. We find that asset maturity, security covenants, and macroeconomic conditions influence the new issue maturity of bonds within rating categories.

The number of river restoration projects undertaken in the UK has increased rapidly over the last five years. However, schemes are still largely undertaken on an ad-hoc basis rather than part of a co-ordinated, strategic, catchment restoration strategy. Additionally, project level restoration is rarely initiated through a systematic approach that involves all stages from baseline studies through to design, installation, monitoring and post-project appraisals. The need for both strategic and project levels to be undertaken effectively is necessary if the requirements of the Water Framework Directive (WFD) are to be met. This directive has the potential to significantly increase the number of schemes, as restoration of surface water bodies has become a key duty of member states. There exists, therefore, a need for a holistic catchment scale approach to restoration to be adopted to maximise benefit to the fluvial systems and ensure compliance. This paper outlines key components of strategic and project level protocols for river restoration from a UK perspective.

We argue that the appropriate discount rate used to report defined benefit pension plan liabilities in the financial statements is a yield derived from an estimate of a double A corporate yield curve. We show that parsimonious yield curve techniques are easily applicable to the sterling double A corporate bond market. Moreover we find that with a careful selection of the data an objective and reliable yield curve can be obtained. In all we find that using a yield from a sterling double A corporate yield curve to obtain the value of defined benefit pension plan liabilities is a feasible alternative to the current recommendations of FRS17. JEL classification : M41, G22, G23. Key Words : FRS17, Corporate Yield Curves, valuation of defined benefit liabilities. Author Details Frank is a Reader at the ISMA Centre, School of Business, University of Reading, Whiteknights Park Reading, RG6 6BA, tel: +44 (0) 1189 316407, f.skinner@ismacentre.reading.ac.uk Michalis Ioannides is a specialist consultant at Watson Wyatt LLP, Watson House, London Road, Reigate, Surrey, RH 2 9PQ, tel: +44 (0) 1737 241144, fax: +44 (0)1737 241496, Michalis.ioannides@eu.watsonwyatt.com. Address all correspondence to Frank Skinner. We would like to thank Watson Wyatt for funding this research. Any errors are our own. This discussion paper is a preliminary version designed to generate ideas and constructive comment. The contents of the paper are presented to the reader in good faith, and neither the author, the ISMA Centre, nor the University, will be held responsible for any losses, financial or otherwise, resulting from actions taken on the basis of its content. Any persons reading the paper are deemed to have accepted this.

Protein tyrosine phosphatase 1B (PTPN1) affects the regulation of insulin signaling and energy metabolism. We studied whether polymorphisms in the PTPN1 gene impact body fat distribution in the HERITAGE Family Study cohort in 502 white and 276 black subjects. Insulin sensitivity index, glucose disappearance index, acute insulin response to glucose (AIR(glucose)), and the disposition index (DI) were obtained from the frequently sampled intravenous glucose tolerance test. White subjects with the G82G at the PTPN1 IVS6+G82A polymorphism had higher body fat levels (p = 0.031) and sum of eight skinfolds (p = 0.003) and highest subcutaneous fat on the limbs (p = 0.002). G82A subjects had the lowest AIR(glucose) (p = 0.005) and disposition index (p = 0.040). Interaction effects between PTPN1 and leptin receptor gene variants influenced insulin sensitivity index and AIR(glucose) (p from 0.006 to 0.010). The variant PTPN1 Pro387Leu was associated with lower fasting insulin level (p = 0.035) and glucose disappearance index (p = 0.038). In summary, PTPN1 IVS6+G82G homozygotes showed higher levels of all measures of adiposity. G82 allele heterozygotes are potentially at higher risk for type 2 diabetes. Gene-gene interactions between the PTPN1 and leptin receptor genes contributed to the phenotypic variability of insulin sensitivity. The PTPN1 Pro387Leu variant was associated with lower glucose tolerance.

Objective: To investigate familial basis for the relationship between cortisol adiposity at baseline and their training responses. Research Methods and Procedures: Bivariate correlation and segregation analyses were employed between cortisol and several adiposity measures [body mass index, fat mass (FM), fat-free mass, percentage of body fat (% BF), abdominal visceral fat (AVF), abdominal subcutaneous fat (ASF), and abdominal total fat (ATF)] from 99 white families and 105 black families. Results: In both races, significant inverse phenotypic correlations were generally observed between cortisol and adiposity measures at baseline but not for training responses. Significant cross-trait familial correlations were found for cortisol with abdominal fat (ASF, AVF, ATF) and overall body adiposity (FM, % BF) measures at baseline, which accounted for 14% to 20% of the phenotypic variance in whites. The cross-trait correlations were not significant for baseline phenotypes in blacks, perhaps because of the small sample size. A bivariate segregation analysis showed evidence of polygenic pleiotropy for cortisol with both abdominal fat and overall adiposity measures that accounted for 14% to 17% of the phenotypic covariance, but major gene pleiotropy was not suggested in whites. However, when ASF, AVF, and ATF were additionally adjusted for FM, no familial cross-trait correlations or polygenic pleiotropy between cortisol and the abdominal fat measures remained. Discussion: Evidence was found for polygenic pleiotropy but not for pleiotropic major gene effects between cortisol and overall adiposity in whites. However, the covariation of cortisol with abdominal fat phenotypes is dependent on concomitant polygenic factors for total-body fat.

Associations between preproghrelin DNA variants and obesity-related phenotypes were studied in 3004 subjects from the Québec Family Study (QFS), the HERITAGE Family Study (HERITAGE), and the Swedish Obese Subjects (SOS) Study.Body mass index (BMI), fat mass (FM) from underwater weighing, and abdominal fat from computerized tomography were measured. The ghrelin polymorphisms were identified by polymerase chain reaction.Arg51Gln QFS subjects (n = 6) had lower ghrelin concentrations (p = 0.007) than Arg51Arg subjects (n = 14). White preproghrelin Met72Met subjects in HERITAGE had the lowest BMI (p = 0.020), and those in the QFS cohort had the lowest FM (p0.001). Met72 carrier status (Met72+) was associated with lower FM (p = 0.026) and higher insulin-like growth factor-1 levels (p = 0.019) among blacks. Met72Met QFS subjects had less visceral fat (p = 0.002) and a lower fasting respiratory quotient (p = 0.037). HERITAGE Met72+ white subjects also showed lower exercise respiratory quotient (p = 0.030) and higher maximal oxygen uptake (p = 0.023). Furthermore, the prevalence of Met72+ was higher (19.2%; p0.05) in SOS subjects whose BMI wasor =25 kg/m(2) than in those with BMI25 kg/m(2) (14.8%). SOS Met72+ obese women had a lower (11.4%; p = 0.032) prevalence of hypertension than noncarriers (23.9%).Arg51Gln mutation was associated with lower plasma ghrelin levels but not with obesity. The preproghrelin Met72 carrier status seems to be protective against fat accumulation and associated metabolic comorbidities.

Objective: Previous studies show a wide range in the percentage of variance in leptin levels attributable to genetic factors. These studies differ markedly with respect to ethnicity, study design, and statistical methodology. Therefore, the purpose of this study was to investigate heterogeneity hypotheses across ethnic groups and by adiposity level, using the same statistical methods. Research Methods and Procedures: Samples included black vs. white (HERITAGE Family Study) and random vs. obese (Quebec Family Study) individuals from 432 families (1432 individuals). Heritability for leptin, alternatively adjusted for age and sex and then for age, sex, and adiposity was estimated with the use of familial correlations. Heterogeneity in the magnitude of the familial resemblance between samples and the effect of adjusting for adiposity was explored. Results: Heritability did not vary across samples stratified by adiposity level or ethnic group or across adjustment schemes. Maximal heritability, the percentage of additive phenotypic variability due to all familial sources, was 32%. Discussion: Whereas leptin and adiposity were highly correlated within individuals, removing the effects of adiposity did not significantly alter the magnitude of the familial component for leptin. Moreover, this effect did not vary as a function of ethnicity (black vs. white) or adiposity level. Thus, no evidence for heterogeneity was detected. However, a comparison among previous studies raises questions concerning possible genetic heterogeneity in other ethnic groups in which complex interactions among leptin, adiposity, and diabetes status may be important.

A small series of histone deacetylase (HDAC) inhibitors (VI) are synthesized and evaluated together with previously described HDAC inhibitors for their antiplasmodial properties.

COGNITION AND BIOMARKERS IN ADULTS WITH A DOUBLE-HIT RISK FOR DEMENTIA: MILD COGNITIVE IMPAIRMENTAND PREDIABETES Laura D. Baker, Angela Hansen, Brenna Cholerton, Jeannine Skinner, Kaycee Sink, Maureen Callaghan, Suzanne Craft, Valerie Wilson, Wake Forest School of Medicine, Winston-Salem, North Carolina, United States; VA Puget Sound Health Care System, Seattle, Seattle, Washington, United States; 3 University of Washington Health Sciences, Seattle, Washington, United States; 4 Vanderbilt School of Medicine, Nashville, Tennessee, United States; Wake Forest School of Medicine, Winston-Salem, North Carolina, United States; VA Puget Sound Health Care System, Seattle, Tacoma, Washington, United States; 7 Wake Forest School of Medicine, Winston-Salem, North Carolina, United States. Contact e-mail: ldbaker@wakehealth.edu

Familial influences were investigated for baseline sex hormone-binding globulin (SHBG) and its response (post-training minus baseline) to a 20-week endurance exercise training program. One hundred, eighty-four participants from 85 Black families in the HERITAGE Family Study (HERITAGE) were analyzed using a familial correlation model. Baseline SHBG values and the training response were adjusted for the effects of age, baseline BMI, testosterone, estradiol, and fasting insulin levels (plus baseline SHBG values for the training response) within four sex-by-generation groups prior to genetic analysis. Baseline SHBG levels were influenced by appreciable familial effects (maximum heritability h2 = 54%) with neither spouse resemblance nor sex and generation differences in the correlations. This estimate is only slightly, but not significantly, smaller than the heritability of 64% reported previously in 428 participants from 99 White families in HERITAGE. In contrast to the modest familial effects for the training response in White participants in HERITAGE (h2 = 25%), there were no evidence of familial resemblance in Blacks in the current study. Furthermore, there was heterogeneity for both baseline SHBG and the training response between Blacks and Whites in the pattern of familial aggregation. In conclusion, baseline SHBG levels are influenced by significant familial effects in both Blacks and Whites, independent of the effects of age, sex, and baseline values of BMI, testosterone, estradiol, and fasting insulin levels. Whereas modest familial effects were detected for the training response in Whites, the lack of similar effects in Blacks may be due to the smaller sample size. Am. J. Hum. Biol. 13:832–837, 2001. © 2001 Wiley-Liss, Inc.

Objective: To investigate the association between the Trp64Arg polymorphism of the β3-adrenergic receptor gene and changes in body composition in response to endurance training. Research Methods and Procedures: Adult sedentary white and black subjects participating in the HERITAGE Family Study were measured before and after 20 weeks on endurance training for the body mass index, fat mass, percentage of body fat, fat-free mass, sum of eight skinfolds, and subcutaneous, visceral, and total abdominal fat areas. The association between the Trp64Arg polymorphism and the response phenotypes, computed as the difference between pre- and post-training values, was tested by analysis of covariance separately in men and women. The gene by race interaction term was also tested. Results: No race differences were observed for allelic and genotype frequencies. Training resulted in significant reduction of body fat in both men and women. No association of the Trp64Arg polymorphism was observed with training-induced changes for any of the body composition phenotypes in both men and women. Discussion: These results suggest that the Trp64Arg polymorphism of the β3-adrenergic receptor gene is not related to changes in body composition in response to exercise training.

Hyperglycaemia is associated with a worse prognosis after myocardial infarction and good blood glucose control in the peri-infarct period has been shown to improve outcome. Our primary study was undertaken with the aims of assessing the prevalence and management of hyperglycaemia in patients admitted with acute chest pain. Ninety-three patients admitted to either Coronary Care (CCU) or Emergency Medical Admission Units (EMAU) with chest pain were studied and of these 14 (15%) had severe hyperglycaemia (>11.0 mmol/L). Blood glucose was not measured in seven (8%) patients and in only 1/14 (7%) patient were established guidelines for the management of hyperglycaemia applied. A revision of management protocol was undertaken and after 18 months we repeated the review of management of hyperglycaemia. Of 114 patients 22 (21%) had severe hyperglycaemia, blood glucose was not measured in ten (9%) and management guidelines were followed in 13 (65%). A major improvement in management of blood glucose in emergency admissions with chest pain has been demonstrated. Further staff education, discussion and review of protocol are indicated to improve and maintain performance on CCU and EMAU. Copyright © 2001 John Wiley & Sons, Ltd.

Objective: To examine whether there is a major gene effect on fasting insulin and pleiotropic loci for fasting insulin, total fat mass (FM), and abdominal visceral fat (AVF). Research Methods and Procedures: A major gene hypothesis for fasting plasma insulin levels was assessed using segregation analyses of data on 495 members in 98 normolipidemic sedentary families of white descent who participated in the HERITAGE Family Study. Results: Segregation analyses were performed on insulin adjusted for age, on insulin adjusted for age and FM, and on insulin adjusted for age and AVF. Before adjustment for AVF and FM, a major gene effect on fasting insulin levels was indicated. The putative locus accounted for 54% of the variance under a recessive inheritance pattern, affecting 11% of the sample (i.e., allele frequency = 0.33). However, after adjusting for the effects of AVF or FM, neither a major effect alone nor a multifactorial component alone could be rejected, and support for a major gene was equivocal, i.e., neither the hypothesis of Mendelian τ values or that of the equal τs were rejected and the equal τ model fit the data better than the Mendelian τ model. This pattern (i.e., major gene evidence for insulin before but not after adjustment for AVF or FM) suggests that there is a putative locus with pleiotropic effects on both insulin and FM and another pleiotropic locus for both insulin and AVF. Discussion: Although these data do not directly support an additional major gene for insulin independent of AVF and FM, such support cannot be ruled out because there is still a significant major effect on FM- or AVF-adjusted insulin (albeit the Mendelian nature of this effect is ambiguous).

Objective: Investigate the familial aggregation of amount and distribution of subcutaneous fat and their changes in response to endurance training. Research Methods and Procedures: A total of 483 sedentary subjects from 99 nuclear families were recruited, trained for 20 weeks of exercising on cycle ergometers, and measured before and after training for the following indicators of subcutaneous fat and fat distribution: trunk fat (TRUNK = sum of abdominal, subscapular, suprailiac, and midaxillary skinfolds), extremity fat (EXTREM = sum of biceps, triceps, thigh, and calf skinfolds), subcutaneous fat (SF8 = sum of the eight skinfolds), the trunk to extremity skinfolds ratio adjusted for SF8 (TER) and waist girth adjusted for body mass index (WAIST). The familial aggregation of the age- and sex-adjusted baseline phenotypes and their responses to training (Δ) after adjustment for the baseline values was investigated using a familial correlation model. Results: Significant familial aggregation was observed for all the phenotypes measured at baseline and for ΔTRUNK and ΔWAIST. Transmissibility estimates reached about 30% to 35% for TRUNK, EXTREM, and SF8 and 50% for TER and WAIST. The transmissibilities of the response phenotypes were lower, ranging from 0% for ΔWAIST to 21% for ΔTRUNK and the pattern of familial correlations suggested a greater within- than between-generation resemblance in the response. Discussion: This study suggests that the amount and distribution of subcutaneous fat strongly aggregates in families, whereas the response to exercise training is characterized by a moderate and more complex pattern of familial resemblance. We conclude that familial/genetic factors are more important in determining the amount and distribution of subcutaneous fat than their responses to exercise training.

Cross-trait familial resemblance between resting blood pressure (BP) and body composition and fat distribution was examined in 98 Caucasian families participating in the HERITAGE Family Study by using a multivariate familial correlation model assessing both intraindividual and interindividual cross-trait correlations. The 520 family members were sedentary at baseline examination, and both resting systolic (SBP) and diastolic (DBP) BP were cross-analyzed with each of the following 10 indications of body composition and fat distribution: percent body fat (%BF), abdominal visceral fat (AVF), body mass index (BMI), fat-free mass (FFM), fat mass (FM), sum of eight skinfolds (SF), total abdominal fat (TAF), ratio of trunk-to-extremity skinfolds (TER), waist circumference (WAIST), ratio of waist-to-hip circumferences (WHR). Five of the variables were also corrected for fat mass (AVFf, TAFf, TERf, WAISTf, WHRf) to index these measures independent of total degree of adiposity. In general, the results suggested strictly intraindividual cross-trait resemblance, with occasional spouse cross-trait resemblance, but few or no sibling or parent-offspring cross-trait correlations. This pattern is largely consistent with nongenetic specific environmental determinants for the BP-body composition and fat distribution covariation, with possibly some common environmental influence between spouses and negligible genetic effects. The only findings suggesting any familial cross-trait resemblance were significant sibling correlations for DBP-FFM and DBP-WHR, although the parent-offspring correlation was not significant. These findings suggest that the observed BP-body composition and fat distribution cross-trait correlations in these sedentary families are probably not due to multifactorial effects such as polygenic and/or common familial environmental effects. Whether or not other factors such as nonadditive effects are involved warrants further investigation using other methods. Am. J. Hum. Biol. 12:32-41, 2000. Copyright 2000 Wiley-Liss, Inc.

We examine Treasury bond and stock index futures, the swap curve and two types of hypothetical corporate bond assets as alternative hedging instruments for portfolios of corporate bonds. Conducting ex post and ex ante tests we find evidence that credit quality and maturity are important sources of basis risk when hedging corporate bonds whose credit rating are below triple A. We conclude that a new corporate hedging instrument may be useful for those wishing to hedge corporate bond portfolios provided that transaction costs are not too high relative to existing futures contracts.

Background: Patients with coronary artery disease are managed differently in different countries. Hypothesis: These variations in patient management may affect clinical outcome, a possibility that should be taken into consideration in multicenter studies. Methods: In a binational, 3 months study of antithrombotic treatment of patients with unstable angina and non-Q-wave infarction (ATACS), we compared the experience in the four enrollment centers in the United States (US) with the three centers in the United Kingdom (UK). The 59 US patients and the 299 UK patients were similar with regard to age, rates of prior revascularization, prior positive exercise tests, medication use, and aspirin use. Results: US patients were more commonly women (45 vs. 28%), diabetic (30 vs. 4%), or hypertensive (52 vs. 31%), and had a prior coronary angiogram (30 vs. 18%). After enrollment, coronary angiography was performed more frequently in the US than in the UK (61 vs. 22%). Although the distribution of coronary disease was similar, revascularization without recurrent angina (19 vs. 4%, p

Environmental systems are inherently unstable over time-scales appropriate to planning and management. As knowledge relating to rivers and their floodplains increases, uncertainty is increased rather than decreased. As the limits of what is known become defined, a better appreciation of what is not known is gained. The creation of wildlife habitats in rivers and on floodplains has been referred to as an art rather than a science. This paper highlights some of the many questions which remain unanswered as environmental managers strive for more sustainable and cost-effective projects.

Forming top quintile portfolios on the Sharpe ratio, the alpha, the information ratio, the excess manipulation proof performance measure EMPPM and the doubt ratio; we find that these portfolios persistently outperform similarly constructed mediocre third quintile portfolios throughout the twelve year period from January 31, 2001 to December 31, 2012. However, performance is more modest and less persistent when forming portfolios on the EMPPM. It is clear than when selecting funds according to the ranking by the Sharpe and the information ratio, investors are also selecting funds that have suspicious returns. In contrast, portfolios formed on the alpha and especially the EMPPM has much less excess doubt that more rarely persist.

A major gene hypothesis for abdominal visceral fat (AVF) level, both before and after adjustment for total body fat mass, was investigated in 86 white families who participated in the HERITAGE Family Study. In this study, sedentary families were tested for a battery of measures (baseline), endurance exercise trained for 20 weeks, and then remeasured again. The baseline measures reported here are unique in that the variance due to a potentially important environmental factor (activity level) was limited. AVF area was assessed at L4 to L5 by the use of computerized tomography scan, and total body fat mass was assessed with underwater weighing. For fat mass, a putative locus accounted for 64% of the variance, but there was no evidence of a multifactorial component (i.e., no polygenic and/or common familial environmental effects). For AVF area, both a major gene effect accounting for 54% of the variance and a multifactorial component accounting for 17% of the variance were significant. However, after AVF area was adjusted for the effects of total level of body fat, the support for a major gene was reduced. In particular, there was a major effect for fat mass-adjusted AVF area, but it was not transmitted from parents to offspring (i.e., the three transmission probabilities were equal). The importance of this study is twofold. First, these results confirm a previous study that suggested that there is a putative major locus for AVF and for total body fat mass. Second, the findings from the HERITAGE Family Study suggest that the factors underlying AVF area in sedentary families may be similar to those in the population at large, which includes both sedentary and active families. Whether the gene(s) responsible for the high levels of AVF area is the same as that which influences total body fat content remains to be further investigated.

The HERITAGE (HEalth, RIsk factors, exercise Training And GEnetics) Family Study is a multicenter clinical trial conducted by five institutions in the United States and Canada. The overall objective of the study is to investigate the role of the genotype in cardiovascular, metabolic, and hormonal responses to aerobic exercise training and the contribution of regular exercise to changes in cardiovascular disease and diabetes risk factors in white and black families. Since the accuracy of the assessment of the response to training depends on how repeatable or reproducible the measurements are, it is important to assess potential racial differences in reproducibilities, which may have implications for pooling data across races. The sample studied consisted of 96 blacks and 304 whites. The black sample had 46 males with mean age 33.6 ± 14.2 years and 40 females with mean age 33.9 ± 12.7 years. The white sample had 152 males with mean age 35.5 ± 14.9 years, and 152 females with mean age 34.9 ± 14.3 years. Reproducibilities, as measured by intraclass correlations among repeated measures, were comparable between whites and blacks for variables in the anthropometry, i.e, lipid, exercise test, and blood pressure domains. Reproducibilities in both races exceeded 0.85 for most of the variables. When the within-race reproducibilities are very high, statistical significance of any observed racial difference in the reproducibilities may not be very meaningful. There was a significant racial difference in the reproducibility for Apoprotein A1 (0.73 in blacks, 0.89 in whites, P < 0.01). However, this is not a cause for concern, since only one among 37 comparisons was significant. Am. J. Hum. Biol. 9:415-424, 1997. © 1997 Wiley-Liss, Inc.

This work develops and empirically estimates models of bond yields subject to default risk. Parameters for the probability of survival and the recovery rate subsequent to default are included in a model of corporate bond yields that allow a study of interactions among them. The municipal version of the model includes the tax rate as an additional factor. Empirical evidence is found that supports the notion that both dimensions of default, considered jointly, are related to bond quality. In addition, statistically significant differences in tax rates suggest that higher tax rates are associated with higher grade municipal bonds.

This article marks the tercentenary of the birth of Francis Hutcheson (1694-1746). It is divided into three sections. The first part of the argument reviews aspects of Hutcheson's treatment of moral philosophy that are essential to the understanding of the economic analysis. The second section considers Hutcheson's treatment of interrelated topics such as the division of labor, property risks, value, and money--tracing in each case the debt to Samuel Pufendorf. The concluding section explores Adam Smith's possible debts to his teacher, especially with reference to the treatment of value. Copyright 1995 by Scottish Economic Society.

A series of para-substituted 3-phenyl pyrazolopyrimidines was synthesized and evaluated as inhibitors of lck. The nature of the substitution affected enzyme selectivity and potency for lck, src, kdr, and tie-2. The para-phenoxyphenyl analogue 2 is an orally active lck inhibitor with a bioavailability of 69% and exhibits an extended duration of action in animal models of T cell inhibition.