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Traumatic insemination is a mating behavior during which the (sperm) donor uses a traumatic intromittent organ to inject an ejaculate through the epidermis of the (sperm) recipient, thereby frequently circumventing the female genitalia. Traumatic insemination occurs widely across animals, but the frequency of its evolution, the intermediate stages via which it originates, and the morphological changes that such shifts involve remain poorly understood. Based on observations in 145 species of the free-living flatworm genus Macrostomum, we identify at least nine independent evolutionary origins of traumatic insemination from reciprocal copulation, but no clear indication of reversals. These origins involve convergent shifts in multivariate morphospace of male and female reproductive traits, suggesting that traumatic insemination has a canalizing effect on morphology. We also observed sperm in both the sperm receiving organ and within the body tissue of two species. These species had intermediate trait values indicating that traumatic insemination evolves through initial internal wounding during copulation. Finally, signatures of male-female coevolution of genitalia across the genus indicate that sexual selection and sexual conflict drive the evolution of traumatic insemination, because it allows donors to bypass postcopulatory control mechanisms of recipients.

Why some animals can regenerate while many others cannot remains a fascinating question. Even amongst planarian flatworms, well-known for their ability to regenerate complete animals from small body fragments, species exist that have restricted regeneration abilities or are entirely regeneration incompetent. Towards the goal of probing the evolutionary dynamics of regeneration, we have assembled a diverse live collection of planarian species from around the world. The combined quantification of species-specific head regeneration abilities and comprehensive transcriptome-based phylogeny reconstructions reveals multiple independent transitions between robust whole-body regeneration and restricted regeneration in the freshwater species. Our demonstration that theRNAi-mediated inhibition of canonical Wnt signalling can nevertheless bypass all experimentally tractable head regeneration defects in the current collection indicates that the pathway may represent a hot spot in the evolution of planarian regeneration defects. Combined with our finding that Wnt signalling has multiple roles in the reproductive system of the model speciesS. mediterranea, this raises the possibility of a trade-off between egg-laying and asexual reproduction by fission/regeneration as a driver of regenerative trait evolution. Although initial quantitative comparisons of Wnt signalling levels, reproductive investment, and regenerative abilities across the collection confirm some of the model’s predictions, they also highlight the diversification of molecular mechanisms amongst the divergent planarian lineages. Overall, our study establishes a framework for the mechanistic evolution of regenerative abilities and planarians as model taxon for comparative regeneration research.

Sexual conflicts over the post-mating fate of received ejaculate can favour traits in one sex that are costly to the other. Reciprocally mating hermaphrodites face unique challenges as they mate simultaneously in both the male and female role, potentially leading to receipt of unwanted ejaculate. Reciprocal mating can then give rise to postcopulatory female resistance traits that allow manipulation of received ejaculate. A putative example is the suck behaviour, observed in the flatworm genus Macrostomum. It involves the sperm recipient placing its pharynx over its own female genital opening and appearing to suck, likely removing received ejaculate after mating. The genus also contains hypodermically-inseminating species that presumably exhibit unilateral mating and have not been observed to suck. Here, we examine the evolution of the suck behaviour in Macrostomum, aiming to document the mating behaviour in 64 species. First, we provide videographic evidence that ejaculate is indeed removed during the suck behaviour in a reciprocally mating species, Macrostomum hamatum. Next, we show evolutionary positive correlations between the presence, duration and frequency of reciprocal mating behaviour and the suck behaviour, providing clear evidence that the suck behaviour co-evolves with reciprocal mating behaviour. Finally, we show an association between reproductive behaviour and reproductive morphology, suggesting that reproductive morphology can be used for inferring the behavioural mating strategy of a species. Together our study demonstrates sexual antagonistic coevolution leading to the evolution of a postcopulatory behavioural trait that functions as a female counter-adaptation allowing individuals to gain control over received ejaculate in a hermaphroditic sexual system.

Behind the inevitable headlines describing the ‘lucky discovery’ of the Sinclair Pollucite Deposit by Pioneer Resources in a drilling campaign targeting lithium mineralisation, the identification, ...

Background:Sex allocation is the distribution of resources to male or female reproduction. In hermaphrodites, this concerns an individual’s resource allocation to, for example, the production of male or female gametes. Macroevolutionary studies across hermaphroditic plants have revealed that the self-pollination rate and the pollination mode are strong predictors of sex allocation. Consequently, we expect similar factors such as the selfing rate and aspects of the reproductive biology, like the mating behaviour and the intensity of postcopulatory sexual selection, to predict sex allocation in hermaphroditic animals. However, comparative work on hermaphroditic animals is limited. Here, we study sex allocation in 120 species of the hermaphroditic free-living flatworm genus Macrostomum. We ask how hypodermic insemination, a convergently evolved mating behaviour where sperm are traumatically injected through the partner’s epidermis, affects the evolution of sex allocation. We also test the commonly-made assumption that investment into male and female reproduction should trade-off. Finally, we ask if morphological indicators of the intensity of postcopulatory sexual selection (female genital complexity, male copulatory organ length, and sperm length) can predict sex allocation.Results:We find that the repeated evolution of hypodermic insemination predicts a more female-biased sex allocation (i.e., a relative shift towards female allocation). Moreover, transcriptome-based estimates of heterozygosity reveal reduced heterozygosity in hypodermically mating species, indicating that this mating behavior is linked to increased selfing or biparental inbreeding. Therefore, hypodermic insemination could represent a selfing syndrome. Furthermore, across the genus, allocation to male and female gametes is negatively related, and larger species have a more female-biased sex allocation. Finally, increased female genital complexity, longer sperm, and a longer male copulatory organ predict a more male-biased sex allocation.Conclusions:Selfing syndromes have repeatedly originated in plants. Remarkably, this macroevolutionary pattern is replicated in Macrostomum flatworms and linked to repeated shifts in reproductive behavior. We also find a trade-off between male and female reproduction, a fundamental assumption of most theories of sex allocation. Beyond that, no theory predicts a more female-biased allocation in larger species, suggesting avenues for future work. Finally, morphological indicators of more intense postcopulatory sexual selection appear to predict more intense sperm competition.

Free-living flatworms of the genus Macrostomum are small and transparent animals, representing attractive study organisms for a broad range of topics in evolutionary, developmental, and molecular biology. The genus includes the model organism M. lignano for which extensive molecular resources are available, and recently there is a growing interest in extending work to additional species in the genus. These endeavours are currently hindered because, even though >200 Macrostomum species have been taxonomically described, molecular phylogenetic information and geographic sampling remain limited. We report on a global sampling campaign aimed at increasing taxon sampling and geographic representation of the genus. Specifically, we use extensive transcriptome and single-locus data to generate phylogenomic hypotheses including 145 species. Across different phylogenetic methods and alignments used, we identify several consistent clades, while their exact grouping is less clear, possibly due to a radiation early in Macrostomum evolution. Moreover, we uncover a large undescribed diversity, with 94 of the studied species likely being new to science, and we identify multiple novel morphological traits. Furthermore, we identify cryptic speciation in a taxonomically challenging assemblage of species, suggesting that the use of molecular markers is a prerequisite for future work, and we describe the distribution of putative synapomorphies and suggest taxonomic revisions based on our finding. Our large-scale phylogenomic dataset now provides a robust foundation for comparative analyses of morphological, behavioural and molecular evolution in this genus., Molecular Phylogenetics and Evolution, 166, ISSN:1055-7903, ISSN:1095-9513

Sex allocation is the distribution of resources to male or female reproduction. In hermaphrodites, this concerns an individual's resource allocation to, for example, the production of male or female gametes. Macroevolutionary studies across hermaphroditic plants have revealed that the self-pollination rate and the pollination mode are strong predictors of sex allocation. Consequently, we expect similar factors such as the selfing rate and aspects of the reproductive biology, like the mating behaviour and the intensity of postcopulatory sexual selection, to predict sex allocation in hermaphroditic animals. However, comparative work on hermaphroditic animals is limited. Here, we study sex allocation in 120 species of the hermaphroditic free-living flatworm genus Macrostomum. We ask how hypodermic insemination, a convergently evolved mating behaviour where sperm are traumatically injected through the partner's epidermis, affects the evolution of sex allocation. We also test the commonly-made assumption that investment into male and female reproduction should trade-off. Finally, we ask if morphological indicators of the intensity of postcopulatory sexual selection (female genital complexity, male copulatory organ length, and sperm length) can predict sex allocation.We find that the repeated evolution of hypodermic insemination predicts a more female-biased sex allocation (i.e., a relative shift towards female allocation). Moreover, transcriptome-based estimates of heterozygosity reveal reduced heterozygosity in hypodermically mating species, indicating that this mating behavior is linked to increased selfing or biparental inbreeding. Therefore, hypodermic insemination could represent a selfing syndrome. Furthermore, across the genus, allocation to male and female gametes is negatively related, and larger species have a more female-biased sex allocation. Finally, increased female genital complexity, longer sperm, and a longer male copulatory organ predict a more male-biased sex allocation.Selfing syndromes have repeatedly originated in plants. Remarkably, this macroevolutionary pattern is replicated in Macrostomum flatworms and linked to repeated shifts in reproductive behavior. We also find a trade-off between male and female reproduction, a fundamental assumption of most theories of sex allocation. Beyond that, no theory predicts a more female-biased allocation in larger species, suggesting avenues for future work. Finally, morphological indicators of more intense postcopulatory sexual selection appear to predict more intense sperm competition.

Sexual selection drives the evolution of many striking behaviours and morphologies, and should leave signatures of selection at loci underlying these phenotypes. However, while loci thought to be under sexual selection often evolve rapidly, few studies have contrasted rates of molecular sequence evolution at such loci across lineages with different sexual selection contexts. Furthermore, work has focused on separate sexed animals, neglecting alternative sexual systems. We investigate rates of molecular sequence evolution in hermaphroditic flatworms of the genus Macrostomum. Specifically, we compare species that exhibit contrasting sperm morphologies, strongly associated with multiple convergent shifts in the mating strategy, reflecting different sexual selection contexts. Species donating and receiving sperm in every mating have sperm with bristles, likely to prevent sperm removal. Meanwhile, species that hypodermically inject sperm lack bristles, potentially as an adaptation to the environment experienced by hypodermic sperm. Combining functional annotations from the model, M. lignano, with transcriptomes from 97 congeners, we find genus-wide faster sequence evolution in reproduction-related versus ubiquitously-expressed genes, consistent with stronger sexual selection on the former. Additionally, species with hypodermic sperm morphologies had elevated molecular sequence evolution, regardless of a gene’s functional annotation. These genome-wide patterns suggest reduced selection efficiency following shifts to hypodermic mating, possibly due to higher selfing rates in these species. Moreover, we find little evidence for convergent amino acid changes across species. Our work not only shows that reproduction-related genes evolve rapidly also in hermaphroditic animals, but also that well-replicated contrasts of different sexual selection contexts can reveal underappreciated genome-wide effects.

Traumatic insemination is a mating behaviour during which the (sperm) donor uses a traumatic intromittent organ to inject an ejaculate through the epidermis of the (sperm) recipient, thereby frequently circumventing the female genitalia. It likely evolves due to sexual selection and sexual conflict, since it allows the donor to bypass pre- and postcopulatory choice and resistance mechanisms of the recipient. Several striking cases of traumatic insemination have been studied to date, but the frequency of its evolution, the intermediate stages via which it originates, and the morphological changes that such shifts involve remain poorly understood. Based on observations of reproductive traits in 145 species of the free-living flatworm genus Macrostomum, in combination with a robust phylogenomic phylogeny, we present comparative work on the evolution of traumatic insemination. We identify at least nine, but up to 13, independent origins of traumatic insemination, which involve convergent shifts in both sperm design and male and female genital morphology. We further find that traumatic insemination may originate via internal wounding. Finally, we highlight the large diversity of reproductive traits across the genus and show evidence for male-female coevolution. Our findings indicate that sexual selection and sexual conflict repeatably favour the evolution of behaviours, like traumatic insemination, that allow donors to bypass control mechanisms of recipients, leading to predictable shifts in both male and female reproductive traits.

BackgroundIn contrast with the setting of acute myocardial infarction, there are limited data regarding the impact of diabetes mellitus on clinical outcomes in contemporary cohorts of patients with chronic coronary syndromes. We aimed to investigate the prevalence and prognostic impact of diabetes according to geographical regions and ethnicity.Methods and resultsCLARIFY is an observational registry of patients with chronic coronary syndromes, enrolled across 45 countries in Europe, Asia, America, Middle East, Australia, and Africa in 2009–2010, and followed up yearly for 5 years. Chronic coronary syndromes were defined by ≥1 of the following criteria: prior myocardial infarction, evidence of coronary stenosis >50%, proven symptomatic myocardial ischaemia, or prior revascularization procedure.Among 32 694 patients, 9502 (29%) had diabetes, with a regional prevalence ranging from below 20% in Northern Europe to ∼60% in the Gulf countries. In a multivariable-adjusted Cox proportional hazards model, diabetes was associated with increased risks for the primary outcome (cardiovascular death, myocardial infarction, or stroke) with an adjusted hazard ratio of 1.28 (95% confidence interval 1.18, 1.39) and for all secondary outcomes (all-cause and cardiovascular mortality, myocardial infarction, stroke, heart failure, and coronary revascularization). Differences on outcomes according to geography and ethnicity were modest.ConclusionIn patients with chronic coronary syndromes, diabetes is independently associated with mortality and cardiovascular events, including heart failure, which is not accounted by demographics, prior medical history, left ventricular ejection fraction, or use of secondary prevention medication. This is observed across multiple geographic regions and ethnicities, despite marked disparities in the prevalence of diabetes.ClinicalTrials identifierISRCTN43070564

OBJECTIVES: The aim of this exploratory study was to investigate the effect of ethanol, isopropanol and n-propanol on stratum corneum (SC) enzymes and keratinocytes in vitro together with their effects on skin condition and function. METHODS: Activities of kallikrein 5 (KLK5) and phospholipase A2 (PLA2) as well as keratinocyte metabolic activity, interleukin-1α (IL-1α) and tumor necrosis factor-α (TNF-α) were measured in vitro in the presence and absence of the different alcohols. We also measured transepidermal water loss (TEWL), skin capacitance, visual dryness and visual redness on the volar forearms of 25 Caucasian women following application of the alcohols 20 and 100 times per day over a period of 14 days in a clinical study. RESULTS: Reduced activities of KLK5 and PLA2 were observed in the presence of the alcohols. The greatest denaturing effect was always observed for n-propanol (P isopropanol > ethanol. At the high application frequencies, the effect of the different alcohols on transepidermal water loss (TEWL) and skin capacitance was similar, but at the low application frequencies, n-propanol had a significant effect on TEWL and capacitance values (P

Halictid bees are good systems for studying the evolution and maintenance of eusociality, because they form small societies where females have multiple behavioural options (stay or leave, reproduce or help). Here, we investigate colony organization, inter-nest movements and patterns of reproduction in Halictus scabiosae, a species where foundresses rear a first brood of females that often behave as helpers to rear a second brood. Using non-destructive sampling and microsatellite genotyping, we monitored the genotypic composition of a sample of colonies over the entire reproductive season, which allowed us to reconstruct sibships and infer parentage within and across colonies. We detected that foundresses and females from the first brood often moved to foreign colonies. Moreover, foundresses were frequently replaced. At least 5 % of the females from the first brood reproduced. Eight of the ten cases of reproduction by first brood females occurred in foreign colonies. Because of extensive bee movements, many colonies contained offspring from unrelated individuals. The average genetic relatedness among bees sampled from the same colony was moderate (0.33 ± 0.02). The relatedness of the second brood to their colony foundresses and first brood females was only 0.14 and 0.21, respectively. The labile colony membership decreases the intra-colony relatedness and thus the inclusive fitness of helpers, but the behavioural flexibility of these bees may allow them to cope with variable environmental constraints.

The aim of this exploratory study was to investigate the effect of ethanol, isopropanol and n-propanol on stratum corneum (SC) enzymes and keratinocytes in vitro together with their effects on skin condition and function.Activities of kallikrein 5 (KLK5) and phospholipase A2 (PLA2) as well as keratinocyte metabolic activity, interleukin-1α (IL-1α) and tumor necrosis factor-α (TNF-α) were measured in vitro in the presence and absence of the different alcohols. We also measured transepidermal water loss (TEWL), skin capacitance, visual dryness and visual redness on the volar forearms of 25 Caucasian women following application of the alcohols 20 and 100 times per day over a period of 14 days in a clinical study.Reduced activities of KLK5 and PLA2 were observed in the presence of the alcohols. The greatest denaturing effect was always observed for n-propanol (P 0.001), and in the case of PLA2, the effect of isopropanol was greater than ethanol (P 0.001). Equally, ethanol had the mildest effects on keratinocyte metabolic activity and cytokine secretion (P 0.001) and n-propanol always produced the most severe changes in normal and differentiated keratinocytes. These in vitro findings supported the clinical results where the major effects were on the induction of skin irritation (increased dropout rates) and ranked the intolerance of the different alcohols as follows: n-propanol isopropanol ethanol. At the high application frequencies, the effect of the different alcohols on transepidermal water loss (TEWL) and skin capacitance was similar, but at the low application frequencies, n-propanol had a significant effect on TEWL and capacitance values (P 0.05). Equally, n-propanol and isopropanol produced significantly more skin redness at the low application frequencies.Clearly, isopropanol and n-propanol caused significant SC and keratinocyte perturbation in vitro together with damage to skin condition and function in vivo whereas ethanol did not. As a result, we show that ethanol-based sanitizers are better tolerated by skin, particularly in high-use settings, than other alcohols and should be the active ingredient of choice.

Volatile compounds from the apple, Malus domestica Borkh. (Rosaceae), change considerably as the season progresses, and this is successfully exploited by the female codling moth Cydia pomonella L. (Lepidoptera, Tortricidae), as it searches for oviposition sites. In this study, we investigated the effect of seasonal emissions of apple fruit volatiles on the host location behaviour of a parasitoid of the codling moth larvae, Hyssopus pallidus (Askew) (Hymenoptera: Eulophidae). In dual choice olfactory bioassays, the behaviour of the parasitoid in response to apple cues was observed over the complete 2003 growing season. Our results show that codling moth infested apples evoked a strong response from the parasitoid at the beginning of the season, until July. Then, attraction dropped drastically, increasing again at the beginning of August. At the end of the growing season, just prior to harvest, infested apples hardly evoked any behavioural response. Interestingly enough, mid-season emissions of healthy apples were per se attractive to the parasitoid, and even preferred over volatiles from infested apples. Simultaneous volatile collections from healthy apples on twigs in the field were analysed throughout the season, showing that the overall quantity of headspace volatiles peaks at the beginning of June and mid-August. The seasonal volatile emission is correlated with the behaviour of the parasitoid during the fruit ripening stage. The results are discussed in relation to the use of H. pallidus as a potential biocontrol agent, in order to enhance current integrated pest management (IPM) programs.

Dental anxiety is quite common in the general popu-lation (1–3). It represents a significant cause of fail-ure to consult and use dental care appropriately.While 20–30% dislike visits to a dentist so much thatthey use dental services only in the case of an emer-gency, approximately 5% of the dentally anxiousindividuals demonstrate such an excessive and’unreasonable‘ fear of dental appointments thatthese situations are entirely avoided (1).With regard to the acquisition of clinically signi-ficant dental fears it has been found that the majo-rity of the individuals who are able to recall thecircumstances that led to their condition attributethe onset of their fears to one or more traumaticdental events (4–9). One of these studies showed thatboth the extent to which earlier treatments wereperceived as traumatic, and thefrequency of remem-bered painful incidents, were positively related toreported levels of dental anxiety (5). Thus, painful,aversive or extremely frightening situations serve aspowerful conditioning experiences and thereforeplay an important role in the acquisition of dentalanxiety.Most of the research on traumatic incidents hasnot focused on fears or phobias but on pathologicalstress response syndromes, such as posttraumaticstress disorder (PTSD; 10). The fourth edition of theDiagnostic and Statistical Manual of Mental Disor-ders (DSM-IV), the most widely used psychiatricclassification system, definesPTSD as a disorder thatfollows experiencing, witnessing, or being con-fronted with events involving actual or threateningdeath, physical injury, or other threats to the phy-sical integrity of the self or others (10). To meet thecriteria for PTSD an individual must have beenexposed to a traumatic stressor and have respondedwith a subjective response of fear, helplessnessor horror. The principal clinical feature of PTSDis the painful re-experiencing of the traumaticincident in the form of recurrent and distressing

Summary Seven Hawthorn extracts were tested in isolated guinea pig aorta rings. The effect on noradrenaline- (10 μM) induced contraction was investigated. The extracts were prepared using ethanol (40 to 70% v/v), methanol (40 to 70% v/v), and water as the extraction solvents. The aqueous-alcoholic extracts displayed similar spectra of constituents. They were characterised by similar procyanidin, flavonoid, total vitexin and total phenols content and by similar TLC fingerprint chromatograms. The aqueous extract, however, showed a different fingerprint and a noticeably lower concentration of procyanidins, flavonoids and total phenols but a similar total vitexin content. All 7 extracts had a relaxant effect on the aorta precontracted by noradrenaline and led to relaxations to 44 until 29% of the initial values. The EC50 values of the aqueous-alcoholic extracts varied between 4.16 and 9.8 mg/l. The aqueous extract produced a similarly strong maximal relaxation as the other extracts, but the EC50, at 22.39 mg/l, was markedly higher. The results show that Hawthorn extracts with comparable quality profiles were obtained by using aqueous-alcoholic extraction solvents (40 to 70% ethanol or methanol). The extracts exerted comparable pharmacological effects. When using water as the extraction solvent, both, the spectrum of constituents and the pharmacological effect, deviated remarkably. It is thus possible to obtain bioequivalent extracts with comparable effect profiles by using 40 to 70% ethanol or methanol as the extraction solvent.

Objective To establish a nomogram for fetal penile length during gestation. Design A prospective, cross-sectional study of normal singleton pregnancies. Subjects Four hundred and nineteen male fetuses between 14 and 38 weeks were studied. Methods Measurements of fetal penis length were performed by high resolution transvaginal ultrasonography between 14 and 17 weeks of gestation, and by transabdominal ultrasonography beyond 18 weeks of gestation. Results Adequate penile length measurements were obtained in all 419 fetuses. Penile length as a function of gestational age was expressed by the regression equation: (square root) penile length (mm) = 0.277 + 0.121 × gestational age (weeks). The correlation coefficient, r = 0.967 was found to be highly statistically significant (P < 0.0001). The normal mean and the 90% prediction limits were defined. During the study period, we identified three fetuses with abnormalities involving penile development. Using the above reference data range, it has been shown that their penile length was below the lower limit. Conclusions The present data provide a normal range of fetal penile length from early stages of gestation that may allow intrauterine assessment of the development of the male external genitalia. Copyright © 2001 International Society of Ultrasound in Obstetrics and Gynecology

Small societies of totipotent individuals are good systems in which to study the costs and benefits of group living that are central to the origin and maintenance of eusociality. For instance, in eusocial halictid bees, some females remain in their natal nest to help rear the next brood. Why do helpers stay in the nest? Do they really help, and if yes, is their contribution large enough to voluntarily forfeit direct reproduction? Here, we estimate the impact of helpers on colony survival and productivity in the sweat bee Halictus scabiosae. The number of helpers was positively associated with colony survival and productivity. Colonies from which we experimentally removed one helper produced significantly fewer offspring. However, the effect of helper removal was very small, on average. From the removal experiment, we estimated that one helper increased colony productivity by 0.72 additional offspring in colonies with one to three helpers, while the increase was smaller and not statistically significant in larger colonies. We conclude that helpers do actually help in this primitively eusocial bee, particularly in small colonies. However, the resulting increase in colony productivity is low, which suggests that helpers may be constrained in their role or may attempt to reproduce.

Diabetes and peripheral artery disease (PAD) are acknowledged hallmarks of development of atherosclerotic cardiovascular disease (CVD). The prognostic implications of physical indicators of PAD, compared with and in conjunction with glucose intolerance based on population based data, are not well documented.The influence of carotid and femoral bruits and nonpalpable pedal pulses, with and without glucose intolerance, on development of coronary disease (CHD), congestive heart failure (CHF), and stroke (CVA) was investigated in a cohort of 1672 men and 2264 women ages 47 to 99 years participating in the Framingham Study. Cross-sectional pooling yielded 29,063 2-year person-examination units based on the sample of whom 440 men and 484 women had glucose intolerance develop. Over the 26 years of follow-up, 210 men and 199 women had 1 or more of the specified CVD events. Logistic regression analysis was used to estimate age-adjusted odds ratios comparing incidence of CVD events in subjects with glucose intolerance, signs of PAD, or both conditions with those with neither condition. Glucose intolerance was associated with a 2-fold excess occurrence of physical signs of PAD (P.01 ). Femoral and carotid bruits were generally associated with greater increased risk of CHD, CHF, and CVA than was glucose intolerance alone. Particularly in women, the concomitant presence of bruits augmented the CVD risk of glucose intolerance. Nonpalpable pedal pulses were a stronger risk factor for CVD end points than glucose intolerance; particularly in men and in both sexes, those with both conditions were at substantially greater risk of CVD events than those with either alone.Physical findings of PAD appear to signify a compromised arterial circulation to the heart and brain as well as the limbs in persons with glucose intolerance. Persons with the combination are candidates at high risk for CHD, CHF, and CVA.

In the present study, the equivalence of paper and pencil assessment versus computer assessment of two self-administered questionnaires was investigated by means of a randomized cross-over design. Therefore, 105 out-patients with diabetes were invited to participate; 76 patients completed both the computer and the paper and pencil version of the Well-being Questionnaire (WBQ) and the Diabetes Treatment Satisfaction Questionnaire (DTSQ) in a randomized order, with a mean interval of 7 days. The scales showed high test-retest correlations and the means, dispersions, kurtosis and skewness were found to be approximately the same in both versions. In both modes of assessment, the depression and the energy scale proved to be sensitive for carry-over effects, resulting in better well-being scores at the second measurement. Almost all subjects reported that using the personal computer in the realization of a questionnaire was easy. It is concluded that the paper and pencil and the computerized versions of the WBQ and DTSQ can be considered equivalent. Therefore, the norms and cut-off scores obtained from paper and pencil assessments can be used in computerized versions of the WBQ and DTSQ and vice versa.

Angina pectoris before and after MI was evaluated in a sample of 729 men and women from a general population in whom MI developed during a 36-year period of follow-up. Relations of AP to subsequent CHD events and mortality after initial MI were analyzed by proportional hazards regression models and were adjusted for covariates (age, sex, blood pressure, serum cholesterol, body mass index, glucose intolerance, cigarette smoking, and antihypertensive medications) obtained from routine biennial examinations preceding the initial MI. Comparisons of the influence of angina were made between pre-MI angina, post-MI angina, and absence of AP. The sample had 484 men and 245 women (mean ages, 63 and 69, respectively) who survived greater than / equal to 30 days after MI. The initial MI was clinically unrecognized in 165 (34%) men and 115 (47%) women. Data on covariates were complete for 622 subjects, among whom 30% had pre-Ml angina, 18% had post-MI angina, and 52% did not have AP. Angina was half as common in persons with unrecognized MIs as in those with clinically recognized MIs. During an average of 8.7 years of follow-up, 57% of subjects developed subsequent CHD events, including recognized and unrecognized MI, coronary insufficiency, and CHD death, and 74% died. Both pre-MI angina (hazard ratio, 1.49; 95% CI, 1.17 to 1.91) and post-MI angina (hazard ratio, 1.43; 95% CI, 1.06 to 1.94) adjusted for accompanying risk factors were associated with increased risk for subsequent CHD events compared with those without AP. Neither pre-MI nor post-MI angina was associated with excess overall mortality.

Early-stage Hodgkin's lymphoma patients treated with radiotherapy alone or combined modality therapy were retrospectively analyzed for survival, patterns of failure, salvage, and toxicity. Of 75 evaluable patients, 47 were given radiotherapy alone and 28 were given combination radiotherapy and chemotherapy. Of the patients studied, 26 were clinical stage I and 49 were clinical stage II, with nine patients upstaged at laparotomy. Minimum follow-up was 2 years, with a median of 81 months. Complete response rate was 95%. Relapse-free survival and overall survival were 89% and 96%, respectively, at 2 years ; 78% and 86% at 5 years ; and 76% and 82% at 10 years. Of 16 patients who relapsed (21%), 13/47 patients were treated with radiotherapy and 3/28 were treated with combined modality therapy. Salvage rates were higher in those treated with radiotherapy alone. There were 13 deaths : six from disease, two from treatment-related complications, and five from second primary malignancies. There was a higher incidence of second malignancies and deaths due to complication in patients treated with combined modality therapy. Radiotherapy alone or with chemotherapy is an effective modality in the treatment of Hodgkin's lymphoma. Treatment should be selected properly to optimize results and decrease complications.

From 1986 to 1991, 13 patients at Northwestern Memorial Hospital were entered onto a pilot study designed to test the feasibility of treating children with medulloblastoma (11 patients) or primitive neuroectodermal tumors of the cerebral hemispheres (2 patients) with hyperfractionated craniospinal radiotherapy (HFxRT). Follow-up times ranged from 10 to 96 months with a median of 53 months. The patients were prospectively divided among three treatment arms depending on prior treatment history, if any, and degree of surgical resection. The 3 patients in group I had undergone gross total resection of the primary site, receiving 64.8 Gy to the primary site and 31.2 Gy directed to the craniospinal axis (CSA). Of these 3 patients, patient 1 had residual disease in the thoracic spine at T-10. The 8 patients in group II, who had gross residual disease remaining at the primary site, received 72 Gy to the primary site and 34 Gy to the CSA. Five of these eight patients in group II also received 8-in-1 chemotherapy. The 2 patients in group III had already failed chemotherapy and were then treated with 60 Gy to the primary site and 26 Gy to the CSA. Of the 11 patients in groups I and II, 7 of the 11 (64%) have never recurred. Two of the three group-I patients have not recurred, and 5 of the 7 group-II patients have not recurred. In addition, patient 7 (group II) remains alive after salvage with bone marrow transplant, following a local failure bordering the tentorium. Unfortunately, neither of the group-III patients could be salvaged with HFxRT. Acute/subacute toxicities included 7 cases of external auditory canal or skin desquamation, 2 cases of postradiation somnolence, and 1 case each of poor wound healing and neutropenia. Chronic toxicities included hypothyroidism in 2 patients and growth problems in 2 patients. Neuropsychologic complications affected only the 3 youngest patients in the study. Three patients developed neurologic sequelae attributed to radiation, including 1 with progressive urinary incontinence, 1 who developed a transient ischemic attack, and 1 who became progressively ataxic. Our research, although based on a small number of patients, suggests that hyperfractionated radiation therapy to craniospinal access is feasible and that the survival results are favorable. This treatment strategy should be further explored in a phase-III randomized trial.

The PLZF gene was discovered by studying a rearrangement of the RAR alpha locus in a patient with acute promyelocytic leukemia and a t(11;17) chromosomal translocation. To understand further the potential role(s) of the PLZF gene product in hematopoiesis, we have examined its expression levels in a variety of murine tissues and in established cell lines that are representative of various stages of myeloid and lymphoid development. We show that murine PLZF(mPLZF) is expressed at the highest levels in undifferentiated, multipotential hematopoietic progenitor cells and that its expression declines as cells become more mature and committed to various hematopoietic lineages. Data obtained with established cell lines are corroborated by results showing the lack of human PLZF protein expression in mature peripheral blood mononuclear cells and high PLZF levels in the nuclei of CD34+ human bone marrow progenitor cells. Interestingly, unlike many transcription factors, PLZF protein in these cells possesses distinct punctate nuclear distribution, suggesting its compartmentalization in the nucleus. Taken together, our data suggest a role for PLZF protein in early hematopoiesis and the requirement of downregulation of its expression for proper differentiation of most hematopoietic lineages.

Background and Purpose Several studies have shown stroke onset to vary by season, day of the week, and time of day. These temporal patterns, which may provide insights into pathogenesis, were found mainly in clinical series, which can be subject to selection bias. To obtain a less distorted picture of stroke onset, we examined the month and season, day of the week, time, and place stroke occurred in a community-based cohort. Methods Over a 40-year period of surveillance of the Framingham Study cohort of 5070 people aged 30 to 62 years and free of stroke and cardiovascular disease at entry, 637 completed initial strokes occurred. Month, season, day of the week, time of day, and place of occurrence of stroke were ascertained systematically and related prospectively to stroke incidence, subtype, and gender. Results Winter was the peak season for cerebral embolic strokes. Significantly more stroke events occurred on Mondays than any other day, particularly for working men. For intracerebral hemorrhages, a third happened on Mondays in both genders. The time of day when strokes most frequently occurred was between 8 am and noon. This pattern was true for all stroke subtypes. This pattern persisted when individuals whose onset occurred while sleeping or on awakening were excluded. Stroke in general occurred more at home, with hemorrhagic strokes occurring outside the home and cerebral embolisms in the hospital more than other subtypes. Conclusions Temporal patterns of stroke onset were observed for season, day of the week, time of day, and place in a community-based population. These findings suggest that there are periods of increased risk of stroke that may be amenable to preventive strategies.

Introduction Primitively eusocial halictid bees are excellent systems to study the origin of eusociality, because all individuals have retained the ancestral ability to breed independently. In the sweat bee Halictus scabiosae, foundresses overwinter, establish nests and rear a first brood by mass-provisioning each offspring with pollen and nectar. The mothers may thus manipulate the phenotype of their offspring by restricting their food provisions. The first brood females generally help their mother to rear a second brood of males and gynes that become foundresses. However, the first brood females may also reproduce in their maternal or in other nests, or possibly enter early diapause. Here, we examined if the behavioural specialization of the first and second brood females was associated with between-brood differences in body size, energetic reserves and pollen provisions. Results The patterns of variation in adult body size, weight, fat content and food provisioned to the first and second brood indicate that H. scabiosae has dimorphic females. The first-brood females were significantly smaller, lighter and had lower fat reserves than the second-brood females and foundresses. The first-brood females were also less variable in size and fat content, and developed on homogeneously smaller pollen provisions. Foundresses were larger than gynes of the previous year, suggesting that small females were less likely to survive the winter. Conclusions The marked size dimorphism between females produced in the first and second brood and the consistently smaller pollen provisions provided to the first brood suggest that the first brood females are channelled into a helper role during their pre-imaginal development. As a large body size is needed for successful hibernation, the mother may promote helping in her first brood offspring by restricting their food provisions. This pattern supports the hypothesis that parental manipulation may contribute to promote worker behaviour in primitively eusocial halictids.

We examined the relationship between the risk of CVD mortality and morbidity and HCT over a period of 34 years of follow-up in the 5209 men and women in the Framingham cohort. There was an increased risk of all-cause death as well as morbidity and mortality due to CVD in subjects with HCT values in the highest quintile. There was no evidence of a decreased risk of CVD in men with lower than median HCT values, and women actually showed increased risk of CVD events with lower HCT values, indicating a J- or U-shaped relationship between HCT and CVD events. The impact of HCT on CVD events appears to differ for different age groups and by sex. HCT is significantly related to the incidence of CVD, including CHD, MI, angina pectoris, stroke, and IC in younger men. In younger women, HCT is related to the incidence of CVD, CHD, MI, and mortality from CVD and CHD. A negative association with CHF incidence and stroke death is noted in elderly women. These results support the hypothesis that HCT is an important risk factor for some CVD events, an association that merits further investigation.

The genes encoding the photosynthetic cytochrome b6 (petB) and subunit 4 (petD) have been cloned and sequenced from the unicellular, photoheterotrophic, transformable cyanobacterium Synechococcus sp. PCC 7002, formerly designated Agmenellum quadruplicatum. The gene arrangement was found to be similar to that reported in the cyanobacterium Nostoc PCC 7906. The DNA and derived protein sequences were compared to chloroplast and the other cyanobacterial sequences. By pulsed-field electrophoresis, the petBD operon and the petCA operon, encoding the Rieske iron-sulfur protein and cytochrome f, were found to be located on separate, unlinked, Not I-digested DNA fragments. The petBD operon was found on the third largest Not I fragment (NC-325) while the petCA operon was found on the second largest Not I fragment (NB-370). These results suggest the two operons are not in proximity. The 1.35 kb transcript was shown to be light-regulated. Transcripts from cells grown under constant illumination showed a decrease in petB transcript levels to undetectable levels within 2 h after the cells were placed in the dark. Upon reillumination, transcript levels rose to three-fold over that seen initially under constant illumination.

Within this work, we describe our newly developed interrogation scheme for fiber optic sensing applications. This measurement system will be utilized in Ariane launchers for monitoring temperature and mechanical stress distribution during flight. The acquired sensing data can be used to control propulsion unit an thrusters and thereby adapt the flight path in a way that damage on the launcher is prevented. In order to detect the peak wavelength of e.g. fiber Bragg grating (FBG) sensors, a tunable laser source based on a modulated-grating laser diode is able to scan through a more than 40nm wide spectrum in the infrared region. Several sensors with different spectral answers can be placed inside one sensor fiber and then interrogated sequentially. The magnitudes of the reflected intensities depend on the actual sensor position that is determined by the measurand (e.g. temperature). One single sensor is scanned by a variable number of spectral sampling points and the spectral answer of the sensor is then calculated by centroid algorithms. Depending an the spectral width of one sensor, the number of sensors that shall be interrogated and the required sampling points per sensor, a maximum sampling frequency of 240kHz is achievable with our hardware. Contrary to comparable systems, our interrogator is capable of switching to any available wavelength of its spectrum within a couple of nanoseconds. Therefore standard continuous sweeping through the entire spectrum is not necessary. This results in a new measurement scheme, wherein spectral gaps between consecutive sensors do not need to be scanned and can be skipped. Since most of the spectrum consists of the gaps between the sensors, overall measurement time is thereby reduced significantly. One problem arises from this measurement scheme: Due to the fact that the sensor's spectral answers vary in time, a special algorithm for tracking the spectral movement has to be implemented. The scope of this work is the description, implementation and assessment of this new peak tracking procedure. After describing the measurement setup, we will therefore explain the algorithm behind the peak tracking measurement. Afterwards the simulation process is explained and results are shown. Performance obtained by peak tracking compared to standard continuous wavelength scanning is evaluated in detail and further development steps which are necessary to obtain a fully sophisticated interrogation systems are discussed.

We have investigated the potential of an ingestible thermometric system (ITS) for use with a deep heating system. The ingestible sensor contains a temperature-sensitive quartz crystal oscillator. The telemetered signal is inductively coupled by a radiofrequency coil system to an external receiver. The sensors, covered with a protective silicon coating, are 10 mm in diameter and 20 mm long and are energized by an internal silver-oxide battery. Experimental studies were carried out to investigate the accuracy of the system and the extent of reliable operation of these sensors in an electromagnetic environment. Different measurements were repeated for five sensors. Calibration accuracy was verified by comparison with a Bowman probe in the temperature range 30 degrees C to 55 degrees C. Linear regression analysis of individual pill readings indicated a correlation within +/- 0.4 degrees C at 95% prediction intervals in the clinical temperature range of 35 degrees C to 50 degrees C. Further work is required to improve this accuracy to meet the quality assurance guidelines of +/- 0.2 degrees C suggested by the Hyperthermia Physics Center. Response times were determined by the exponential fit of heat-up and cool-down curves for each pill. All curves had correlation coefficients greater than 0.98. Time (mean +/- SE) to achieve 90% response during heat-up was 115 +/- sec. Time to cool-down to 10% of initial temperature was 114 +/- 4 sec. The effect of the external antenna and sensor spacing and the angle of orientation of the sensor relative to the antenna plane were also studied. Electromagnetic interference effects were studied by placing the sensor with a Bowman probe in a cylindrical saline phantom for the tests in an annular phase array applicator. Different power levels at three frequencies--80, 100, and 120 MHz--were used. Accurate temperature readings could not be obtained when the electromagnetic power was on because of interference effects with the receiver. However, the temperatures read with the ITS immediately after the electromagnetic power was switched off correlated well with the Bowman probe readings across the power categories and the three frequencies used. The phantom was heated to steady state, with a Bowman probe placed at the central axis of the cylinder used as control. During the heat-up period and the steady state, the mean difference (+/- SE) between the ITS and Bowman probe was 0.12 degrees C (+/- 0.05 degrees C).(ABSTRACT TRUNCATED AT 400 WORDS)

A new TL extremity dosimetry system optimised for routine personnel monitoring is presented. It was developed at GSF, based on several GSF patents, and consists of a flexible plastic strip type detector holder with permanent ID code containing the phosphor and a PC controlled standard TL reader. The holder is prepared for single use and designed as a finger ring of adjustable size. It is comfortable to wear even under surgical gloves, water and solvent proof, heat resistant up to autoclave temperatures and can be used with all common TL detectors, limited only by their size. Each phosphor is labelled with an automated readable permanent ID code using a newly developed technique for direct inscription of TL crystals, to allow an individual calibration before application. The software controlling the TL reader includes a computerised glow curve deconvolution (CGCD) algorithm for data analysis and a database system. The CGCD algorithm replaces all annealing procedures in additional furnaces and saves up to 65% processing time at the GSF personnel monitoring service, when using LiF:Mg,Ti (TLD-100) TL detectors. The modular system design gives the possibility of modifying all equipment parts, e.g. detector holder, phosphor or TL reader, for the combined use with components from TL systems commonly used at monitoring services. The extremity dosemeter is type tested by the Physikalisch Technische Bundesanstalt (PTB) and is in routine use at the official personnel monitoring service of GSF.

Twenty eight children with herpes simplex encephalitis were followed up for a mean of 5.5 years. Two children died and 26survived, of whom 16 were left with no neurological sequelae and 10 had persistent neurological sequelae. Mean (SD) Glasgow coma score was significantly lower in the patients with neurological sequelae (7.7 (1.5)) and the patients who died (4.5 (0.7)), compared with the patients without neurological sequelae (11 (1.7)).

The purpose of this study was to determine the relationship between diabetes and the development of some peripheral arterial findings--carotid and femoral bruits and nonpalpable pedal pulse--and acute cardiovascular events in 1,196 men and 1,582 women based on 20-year follow-up data in the Framingham Study.For both men and women without diabetes, the incidence of carotid bruits and nonpalapble pedal pulses increased significantly with age (p less than 0.05) without any apparent male predominance. In contrast, diabetic men and women were at an elevated risk of each peripheral arterial condition that was not appreciably different across age groups. Compared with women without diabetes, those with diabetes experienced nearly a twofold excess of femoral bruits (p less than 0.05) and a 50% excess of nonpalpable pedal pulses (p less than 0.01). Among men, diabetes nearly doubled the risk of carotid bruits (p less than 0.05). Those who had both diabetes and symptoms of peripheral arterial disease were at especially high risk of incident cardiovascular events. In particular, nonpalpable pedal pulses were associated with more than a twofold excess of coronary heart disease (p less than 0.05) and stroke (p less than 0.01) in diabetic women and more than a twofold excess of coronary heart disease and cardiac failure in diabetic men (p less than 0.01). Femoral bruits doubled the risk of coronary heart disease in diabetic men (p less than 0.05).We conclude that while diabetes predisposes to various forms and locations of peripheral arterial disease, the enhanced risk of acute cardiovascular events experienced by diabetic patients is increased further when diabetes is accompanied by indications of a peripheral arterial condition. Since signs of peripheral arterial disease may suggest an impending or coexistent atherosclerotic process, careful examination of arterial circulation by evaluating peripheral pulses and assessing whether bruits are present is important.

A case of oculocerebrorenal (Lowe) syndrome is presented in which analysis of the pattern of RFLP suggested that the gene originally mutated in the grandfather' s X-chromosome and became clinically apparent in one of his male grandsons.