Skin and respiratory ill-health attributed to occupational face mask use.

BACKGROUND: Face mask use in the workplace has become widespread since the onset of the Covid-19 pandemic and has been anecdotally linked to adverse health consequences. AIMS: To examine reports of adverse health consequences of occupational face mask use received by The Health and Occupation Research (THOR) network before and after the pandemic onset. METHODS: THOR databases were searched to identify all cases of ill-health attributed to 'face mask' or similar suspected causative agent between 1 January 2010 and 30 June 2021. RESULTS: Thirty two cases were identified in total, 18 reported by occupational physicians and 14 by dermatologists. Seventy-five per cent of cases were reported after the pandemic onset and 91% cases were in the health and social care sector. 25 of the 35 (71%) diagnoses were dermatological, the most frequent diagnoses being contact dermatitis (14 cases) and folliculitis/acne (6 cases). Of the seven respiratory diagnoses, four were exacerbation of pre-existing asthma. CONCLUSIONS: There is evidence of an abrupt increase in reports of predominantly dermatological ill-health attributed to occupational face mask use since the start of the pandemic. Respiratory presentations have also occurred.

Characterizing zoo-housed Bactrian camel (Camelus bactrianus) reproduction using gonadal steroid metabolite analysis in feces.

Millions of people globally depend on camelids, which demands an increased knowledge of their reproduction. We used zoo-housed Bactrian camels (Camelus bactrianus) to better understand camelid reproductive physiology. Our specific objectives were to: 1) validate the use of fecal hormone metabolite analysis to characterize camel reproductive physiology during sexual maturity and pregnancy; and 2) determine the influence of season on male and female reproduction. We collected fecal samples from 1 male and 3 females housed at Lincoln Park Zoo (Chicago, IL, USA) 1 to 2 times per week for 3.5 years. Extracted hormones were analyzed using enzyme immunoassays for progestogen (FPM), estrogen (FEM), and androgen (FAM) metabolite concentrations. One female sexually matured during our study as evidenced by increased FEM baseline. Results demonstrated seasonal effects on male androgen production with FAMs higher (P < 0.05) January to June (mean ± SEM: 664.6 ± 22.6 ng/g wet feces), compared to July to December (401.6 ± 17.5 ng/g wet feces). One female experienced a persistent corpus luteum, a reproductive abnormality, which was identified by prolonged elevated FPM. FPMs increased during pregnancy for two females (452.9 ± 24.9 and 294.4 ± 19.8 ng/g wet feces) with a gestation of 404 d and 442 d, respectively. The third female never conceived. The FEMs varied (P < 0.05) during the year with no clear seasonal patterns (monthly mean range: 213.1-371.0 ng/g wet feces). Fecal hormone metabolite analysis is a validated method for assessing male seasonality and female pregnancy in the Bactrian camel and can for their management and conservation in zoos and the wild.

Molecular Characterization of Mycoplasma pneumoniae Isolates in the United States from 2012 to 2018.

Mycoplasma pneumoniae is a major cause of community-acquired pneumonia. There are limited data in the United States on the molecular epidemiological characteristics of M. pneumoniae We collected 446 M. pneumoniae-positive specimens from 9 states between August 2012 and October 2018. Culture, antimicrobial susceptibility testing, P1 subtyping, and multilocus VNTR (variable-number tandem repeats) analysis (MLVA) were performed to characterize the isolates. Macrolide-resistant M. pneumoniae (MRMp) was detected in 37 (8.3%) specimens. P1 subtype 2 (P1-2) was the predominant P1 subtype (59.8%). P1 subtype distribution did not change significantly chronologically or geographically. The macrolide resistance rate in P1 subtype 1 (P1-1) samples was significantly higher than that in P1-2 (12.9% versus 5.5%). Six P1-2 variants were identified, including two novel types, and variant 2c was predominant (64.6%). P1-2 variants were distributed significantly differently among geographic regions. Classical P1-2 was more frequent in lower respiratory tract specimens and had longer p1 trinucleotide repeats. Classical P1-2 was most common in MRMp (35.7%), while variant 2c was most common in macrolide-susceptible M. pneumoniae (67.5%). Fifteen MLVA types were identified; 3-5-6-2 (41.7%), 4-5-7-2 (35.3%), and 3-6-6-2 (16.6%) were the major types, and four MLVA clusters were delineated. The distribution of MLVA types varied significantly over time and geographic location. The predominant MLVA type switched from 4-5-7-2 to 3-5-6-2 in 2015. MLVA type was associated with P1 subtypes and P1-2 variant types but not with macrolide resistance. To investigate the M. pneumoniae genotype shift and its impact on clinical presentations, additional surveillance programs targeting more diverse populations and prolonged sampling times are required.

Cryopreservation produces limited long-term effects on the nematode Caenorhabditis elegans.

Cryopreservation, the freezing and later warming of biological samples with minimal loss of viability, is important in many scientific disciplines. For some applications, particularly those where there is limited available material, it is critical to ensure the maximal survival rates of cryopreserved materials. Most of the challenges encountered with such techniques take place after the warming process where cryodamage affects cell viability and future development. Here we have used the nematode Caenorhabditis elegans to investigate the effects of cryodamage caused by slow-freezing. We find that freezing results in the death of some worms, with an approximately 40% reduction in the number of worms that develop in the frozen populations, but that the effects on worms that survive are limited. For example, there are no differences in the lifetime fecundity or in lifespan between frozen and control worms, although early fecundity and body size was reduced in frozen worms. Similarly, analyses of body wall muscle structure and of pharyngeal function indicates that muscle development and function are not significantly affected by freezing. We do however determine that freezing increases the rates of matricidal hatching, where progeny hatch within the mother. Overall, these results indicate that, for worms that survive, cryopreservation produces limited long-term effects, but do indicate that some phenotypes could be used in further analyses of the cellular damage induced by cryopreservation.

Macrolide-Resistant Mycoplasma pneumoniae in the United States as Determined from a National Surveillance Program.

There are sparse data to indicate the extent that macrolide-resistant Mycoplasma pneumoniae (MRMp) occurs in the United States or its clinical significance. Between 2015 and 2018, hospitals in 8 states collected and stored respiratory specimens that tested positive for M. pneumoniae and sent them to the University of Alabama at Birmingham, where real-time PCR was performed for detection of 23S rRNA mutations known to confer macrolide resistance. MRMp was detected in 27 of 360 specimens (7.5%). MRMp prevalence was significantly higher in the South and East (18.3%) than in the West (2.1%). A2063G was the predominant 23S rRNA mutation detected. MICs for macrolide-susceptible M. pneumoniae (MSMp) were ≤0.008 µg/ml, whereas MICs for MRMp were 16 to 32 µg/ml. Patients with MRMp infection were more likely to have a history of immunodeficiency or malignancy. Otherwise, there were no other significant differences in the clinical features between patients infected with MRMp and those infected with MSMp, nor were there any differences in radiographic findings, hospitalization rates, viral coinfections, the mean duration of antimicrobial treatment, or clinical outcomes. There was no significant change in MRMp incidence over time or according to age, sex, race/ethnicity, or status as an inpatient or an outpatient. Patients with MRMp were more likely to have received a macrolide prior to presentation, and their treatment was more likely to have been changed to a fluoroquinolone after presentation. This is the first national surveillance program for M. pneumoniae in the United States. Additional surveillance is needed to assess the clinical significance of MRMp and to monitor changes in MRMp prevalence.

Canine recommended breed weight ranges are not a good predictor of an ideal body condition score.

Breed-specific ideal bodyweight range information is widely used by dog owners and breeders as a guideline to ensure animals are within a healthy weight range. Body Condition Scoring, a method used by veterinarians to assess an animal's overall shape with regard to weight is considered to be an excellent method to determine an animal's overall body condition; these values, however, do not always correspond to published weight ranges. Here, the weight, neuter status, age and a nine-point Body Condition Score of a population of 140 purebred dogs were recorded and subsequently analysed to determine whether bodyweight was an effective predictor for Body Condition Scores. This comparison indicated that published recommended, breed-specific body weight ranges are not a good predictor for an ideal BCS and as such, guidelines for owners and breeders need to be systematically reviewed.

Project HELP: a study protocol to pilot test a shared decision-making tool about treatment options for patients with hepatitis C and chronic kidney disease.

BACKGROUND: Recent advances in treatment have given patients with chronic kidney disease (CKD) access to safer and more effective medications to treat comorbid hepatitis C virus (HCV) infection. Given the variety and complexity of treatment options that depend on patients' clinical characteristics and personal preferences, education and decision support are needed to prepare patients better to discuss treatment options with their clinicians. METHODS: Drawing on International Patient Decision Aids Standards guidelines, literature reviews, and guidance from a diverse expert advisory group of nephrologists, hepatologists, and patients, we will develop and test a HCV and CKD decision support tool. Named Project HELP (Helping Empower Liver and kidney Patients), this tool will support patients with HCV and CKD during decisions about whether, when, and how to treat each illness. The tool will (1) explain information using plain language and graphics; (2) provide a step-by-step process for thinking about treating HCV and CKD; (3) tailor relevant information to each user by asking about the individual's stage of CKD, stage of fibrosis, prior treatment, and comorbidities; (4) assess user knowledge and values for treatment choices; and (5) help individuals use and consider information appropriate to their values and needs to discuss with a clinician. A pilot study including 70 individuals will evaluate the tool's efficacy, usability, and likelihood of using it in clinical practice. Eligibility criteria will include individuals who understand and read English, who are at least 18 years old, have a diagnosis of HCV (any genotype) and CKD (any stage), and are considering treatment options. DISCUSSION: This study can identify particular characteristics of individuals or groups that might experience challenges initiating treatment for HCV in the CKD population. This tool could provide a resource to facilitate patient-clinician discussions regarding HCV and CKD treatment options.

Extended low-dose dexamethasone suppression test for diagnosis of atypical Cushing's syndrome in dogs.

The purpose of this study was to evaluate extension of the low-dose dexamethasone suppression (LDDS) test from 8 h to 12 h to detect possible hypercortisolemia associated with atypical hyperadrenocorticism (AHAC). Twelve client-owned dogs were enrolled in the study: 6 healthy dogs (group 1) and 6 dogs with suspected AHAC (group 2). Baseline EDTA plasma samples were collected for endogenous ACTH determination using an immunoradiometric assay. Serum samples were collected before and at 4, 8, 10, and 12 h post-administration of 0.01 mg/kg dexamethasone IV for cortisol concentration determination via chemiluminescent assay. Mean endogenous ACTH concentration did not differ between groups (group 1: 22.4 pg/mL, group 2: 20.0 pg/mL; P > 0.2). Mean baseline cortisol concentration also did not differ significantly between groups (group 1: 3.03 µg/dL, group 2: 4.95 µg/dL; P > 0.2) nor was there any difference in mean cortisol concentration between the groups at any other time point (P > 0.2). The cortisol concentration from 1 dog in group 2 suppressed to 0.7 µg/dL at 8 h but increased to 1.5 µg/dL at 10 h and 3.7 µg/dL at 12 h post-dexamethasone. Based on results of this study, use of an extended LDDS test could not differentiate between healthy dogs and dogs with AHAC. Diagnosis of AHAC should continue to be based on prior established criteria until new testing has been identified.

Time-lapse embryo imaging and morphokinetic profiling: Towards a general characterisation of embryogenesis.

In vitro fertilisation is an effective method of assisted reproductive technology in both humans and certain non-human animal species. In most species, specifically, in humans and livestock, high in vitro fertilisation success rates are achieved via the transfer of embryos with the highest implantation and subsequent developmental potential. In order to reduce the risk of multiple gestation, which could be a result of the transfer of several embryos per cycle, restrictive transfer policies and methods to improve single embryo selection have been implemented. A non-invasive alternative to standard microscopic observation of post-fertilisation embryo morphology and development is time-lapse technology; this enables continuous, uninterrupted observation of embryo development from fertilisation to transfer. Today, there are several time-lapse devices that are commercially available for clinical use, and methods in which time-lapse could be used to improve embryology are continually being assessed. Here we review the use of time-lapse technology in the characterisation of embryogenesis and its role in embryo selection. Furthermore, the prospect of using this technology to identify aneuploidy in human embryos, as well as the use of time-lapse to improve embryological procedures in agriculturally important species such as the pig and cow are discussed.

Cryopreservation of animal oocytes and embryos: Current progress and future prospects.

Cryopreservation describes techniques that permit freezing and subsequent warming of biological samples without loss of viability. The application of cryopreservation in assisted reproductive technology encompasses the freezing of gametes, embryos, and primordial germ cells. Whilst some protocols still rely on slow-freezing techniques, most now use vitrification, or ultra-rapid freezing, for both oocytes and embryos due to an associated decreased risk of damage caused by the lack of ice crystal formation, unlike in slow-freezing techniques. Vitrification has demonstrated its use in many applications, not only following IVF procedures in human embryology clinics but also following in vitro production of embryos in agriculturally important, or endangered animal species, before embryo transfer. Here, we review the various cryopreservation and vitrification technologies that are used in both humans and other animals and discuss the most recent innovations in vitrification with a particular emphasis on their applicability to animal embryology.

An inter-machine comparison of tobacco smoke particle deposition in vitro from six independent smoke exposure systems.

There are several whole smoke exposure systems used to assess the biological and toxicological impact of tobacco smoke in vitro. One such system is the Vitrocell® VC 10 Smoking Robot and exposure module. Using quartz crystal microbalances (QCMs) installed into the module, we were able to assess tobacco smoke particle deposition in real-time. We compared regional deposition across the module positions and doses delivered by six VC 10s in four independent laboratories: two in the UK, one in Germany and one in China. Gauge R&r analysis was applied to the total data package from the six VC 10s. As a percentage of the total, reproducibility (between all six VC 10s) and repeatability (error within an individual VC 10) accounted for 0.3% and 7.4% respectively. Thus Gauge R&r was 7.7%, less than 10% overall and considered statistically fit for purpose. The dose-responses obtained from the six machines across the four different locations demonstrated excellent agreement. There were little to no positional differences across the module at all airflows as determined by ANOVA (except for one machine and at three airflows only). These results support the on-going characterisation of the VC 10 exposure system and suitability for tobacco smoke exposure in vitro.

Progesterone vs placebo therapy for women with epilepsy: A randomized clinical trial.

OBJECTIVE: To assess progesterone treatment of intractable seizures in women with partial epilepsy. METHODS: This randomized, double-blind, placebo-controlled, phase III, multicenter, clinical trial compared the efficacy and safety of adjunctive cyclic natural progesterone therapy vs placebo treatment of intractable seizures in 294 subjects randomized 2:1 to progesterone or placebo, stratified by catamenial and noncatamenial status. It compared treatments on proportions of ≥50% responders and changes in seizure frequency from 3 baseline to 3 treated menstrual cycles. RESULTS: There was no significant difference in proportions of responders between progesterone and placebo in the catamenial and noncatamenial strata. Prespecified secondary analysis showed that the level of perimenstrual seizure exacerbation (C1 level) was a significant predictor of responders for progesterone but not placebo. With increasing C1 levels, responders increased from 21% to 57% with progesterone vs 19% to 20% with placebo. Reductions in seizure frequency correlated with increasing C1 levels for progesterone but not placebo, progressing from 26% to 71% for progesterone vs 25% to 26% for placebo. A prespecified clinically important separation between progesterone and placebo responders (37.8% vs 11.1%; p = 0.037) was realized among 21.4% of women who had C1 level ≥3. CONCLUSION: There was no difference in the primary outcome of ≥50% responder rates between progesterone vs placebo for catamenial or noncatamenial groups. Post hoc findings suggest that the level of perimenstrual seizure exacerbation is a significant predictor of responder rate with progesterone and that progesterone may provide clinically important benefit for a subset of women with perimenstrually exacerbated seizures. CLASSIFICATION OF EVIDENCE: This study provides Class III evidence that cyclic progesterone is ineffective in women with intractable partial epilepsy. Post hoc analysis identified a subset of women with higher levels of perimenstrual seizure exacerbation that were responsive to treatment.

Disruption of nNOS-PSD95 protein-protein interaction inhibits acute thermal hyperalgesia and chronic mechanical allodynia in rodents.

BACKGROUND AND PURPOSE: Post-synaptic density protein 95 (PSD95) contains three PSD95/Dosophilia disc large/ZO-1 homology domains and links neuronal nitric oxide synthase (nNOS) with the N-methyl-D-aspartic acid (NMDA) receptor. This report assesses the effects of disruption of the protein-protein interaction between nNOS and PSD95 on pain sensitivity in rodent models of hyperalgesia and neuropathic pain. EXPERIMENTAL APPROACH: We generated two molecules that interfered with the nNOS-PSD95 interaction: IC87201, a small molecule inhibitor; and tat-nNOS (residues 1-299), a cell permeable fusion protein containing the PSD95 binding domain of nNOS. We then characterized these inhibitors using in vitro and in vivo models of acute hyperalgesia and chronic allodynia, both of which are thought to require nNOS activation. KEY RESULTS: IC87201 and tat-nNOS (1-299) inhibited the in vitro binding of nNOS with PSD95, without inhibiting nNOS catalytic activity. Both inhibitors also blocked NMDA-induced 3',5'-cyclic guanosine monophosphate (cGMP) production in primary hippocampal cultures. Intrathecal administration of either inhibitor potently reversed NMDA-induced thermal hyperalgesia in mice. At anti-hyperalgesic doses, there was no effect on acute pain thresholds or motor coordination. Intrathecal administration of IC87201 and tat-nNOS also reversed mechanical allodynia induced by chronic constriction of the sciatic nerve. CONCLUSIONS AND IMPLICATIONS: nNOS-PSD95 interaction is important in maintaining hypersensitivity in acute and chronic pain. Disruption of the nNOS-PSD95 interaction provides a novel approach to obtain selective anti-hyperalgesic compounds.

Laterality and location influence catamenial seizure expression in women with partial epilepsy.

OBJECTIVE: The temporal distribution of seizures in women with localization-related epilepsy occurs periodically according to a model "clock" with the peak phase of occurrence corresponding to menstrual onset. The location and laterality of the epileptic lesion as well as patient age may affect periodicity. METHODS: Baseline data from seizure and menstrual diaries of approximately 3 months duration were obtained from 100 women enrolled in a trial of hormonal therapy for localization-related epilepsy. Durations of individual cycles were normalized to a common menstrual phase and period. Normalized data were then combined to create distributions evaluated by localization (lobar: temporal [TL], extratemporal [XL], multifocal [MF], unknown), lateralization (left, right, bilateral, unknown), and age. Distributions were evaluated with analysis of variance (ANOVA) and curve-fitted by nonlinear least squares cosinor analysis. RESULTS: A total of 71 patients had TL (left = 25, right = 29, bilateral = 17), 10 XL, 14 MF, and 5 unknown seizure foci. XL and MF seizures occurred randomly across the 28-day cycle. TL seizures (left = 875, right = 706) occurred nonrandomly (ANOVA p = 0.0003) and cyclically with peak occurrence near onset of menses ([value +/- SD] peak = 1.6 +/- 2.3 days, period = 27.0 days). Left-side TL seizures peaked cyclically at onset of menses (ANOVA p = 0.04, peak = 0.0 +/- 3.0 days, period = 30 days); right-side TL seizures occurred randomly. Age did not have a cyclical effect. Women below the median age had a significantly higher seizure rate than those above the median age. CONCLUSION: Circalunar rhythms of seizures in women, and therefore, possibly strategies of hormonal treatments of catamenial epilepsy, vary with the neuroanatomic substrate of the seizure focus.

Valproate and lamotrigine level variation with menstrual cycle phase and oral contraceptive use.

OBJECTIVE: To determine whether 1) combined oral contraceptive (COC) use affects serum levels of valproate (VPA) as well as lamotrigine (LTG) and 2) the naturally occurring high (mid-luteal) and low (early-mid follicular) reproductive steroid level phases of the menstrual cycle might affect antiepileptic drug levels as well. METHODS: This investigation compared serum antiepileptic drug levels at two timepoints during a single menstrual cycle in four groups of women with epilepsy: 12 on VPA, 12 on VPA plus COC (VPA-COC), 12 on LTG, and 12 on LTG plus COC (LTG-COC). RESULTS: Both VPA and LTG levels were lower (p < 0.01) on active COC than on inactive pill with median declines of 23.4% for the VPA-COC group and 32.6% for the LTG-COC group. Serum LTG levels showed a notable but not significant 31.3% median decline during the mid-luteal phase compared to the early-mid follicular phase in the non-COC group. The non-COC valproate group showed the least change of any group between the two measured timepoints with a decline of 8.3% (p = NS). CONCLUSIONS: The findings suggest that valproate (VPA), like lamotrigine (LTG), has substantially and significantly lower serum levels while women take active combined oral contraceptives as compared to inactive pills. Larger sample sizes will be required to determine whether LTG levels may drop significantly also during the luteal (high steroid) phase of natural menstrual cycles and whether VPA levels may show greater stability in levels across the phases of the menstrual cycle.

Modeling heart rate regulation--part II: parameter identification and analysis.

In part I of this study we introduced a 17-parameter model that can predict heart rate regulation during postural change from sitting to standing. In this subsequent study, we focus on the 17 model parameters needed to adequately represent the observed heart rate response. In part I and in previous work (Olufsen et al. 2006), we estimated the 17 model parameters by minimizing the least squares error between computed and measured values of the heart rate using the Nelder-Mead method (a simplex algorithm). In this study, we compare the Nelder-Mead optimization method to two sampling methods: the implicit filtering method and a genetic algorithm. We show that these off-the-shelf optimization methods can work in conjunction with the heart rate model and provide reasonable parameter estimates with little algorithm tuning. In addition, we make use of the thousands of points sampled by the optimizers in the course of the minimization to perform an overall analysis of the model itself. Our findings show that the resulting least-squares problem has multiple local minima and that the non-linear-least squares error can vary over two orders of magnitude due to the complex interaction between the model parameters, even when provided with reasonable bound constraints.

Application of heuristic optimization techniques and algorithm tuning to multilayered sorptive barrier design.

Although heuristic optimization techniques are increasingly applied in environmental engineering applications, algorithm selection and configuration are often approached in an ad hoc fashion. In this study, the design of a multilayer sorptive barrier system served as a benchmark problem for evaluating several algorithm-tuning procedures, as applied to three global optimization techniques (genetic algorithms, simulated annealing, and particle swarm optimization). Each design problem was configured as a combinatorial optimization in which sorptive materials were selected for inclusion in a landfill liner to minimize the transport of three common organic contaminants. Relative to multilayer sorptive barrier design, study results indicate (i) the binary-coded genetic algorithm is highly efficient and requires minimal tuning, (ii) constraint violations must be carefully integrated to avoid poor algorithm convergence, and (iii) search algorithm performance is strongly influenced by the physical-chemical properties of the organic contaminants of concern. More generally, the results suggest that formal algorithm tuning, which has not been widely applied to environmental engineering optimization, can significantly improve algorithm performance and provide insight into the physical processes that control environmental systems.

No detectable genetic correlation between male and female mating frequency in the stalk-eyed fly Cyrtodiopsis dalmanni.

There is much interest in explaining why female insects mate multiply. Females of the stalk-eyed fly Cyrtodiopsis dalmanni can mate several times each day in a lifetime which may span several months. There are many adaptive explanations, but one hypothesis that has received little rigorous empirical attention is that female multiple mating has evolved for non-adaptive reasons as a correlated response to selection for high male mating frequency rather than because of direct or indirect benefits accruing to females. We tested this hypothesis in stalk-eyed flies by measuring the mating frequency of females from lines that exhibited a direct response in males to artificial selection for increased ('high') and decreased ('low') male mating frequency. We found that the mating frequency of high-line females did not differ from that of low-line females. Hence, there was no support for a genetic correlation between male and female mating frequency in this species. Our study suggests that the genes which influence remating may not be the same in the sexes, and that females remate frequently in this species to gain as yet unidentified benefits.

Direct and correlated responses to artificial selection on male mating frequency in the stalk-eyed fly Cyrtodiopsis dalmanni.

Traditionally it was thought that fitness-related traits such as male mating frequency, with a history of strong directional selection, should have little additive genetic variance and thus respond asymmetrically to bidirectional artificial selection. However, recent findings and theory suggest that a balance between selection for increased male mating frequency and opposing selection pressures on physiologically linked traits will cause male mating frequency to have high additive genetic variation and hence respond symmetrically to selection. We tested these hypotheses in the stalk-eyed fly, Cyrtodiopsis dalmanni, in which males hold harems comprising many females and so have the opportunity to mate at extremely high frequencies. We subjected male stalk-eyed flies to artificial selection for increased ('high') and decreased ('low') mating frequency in the presence of ecologically realistic, high numbers of females. High line males mated significantly more often than control or low line males. The direct response to selection was approximately symmetric in the high and low lines, revealing high additive genetic variation for, and no significant genetic constraints on, increased male mating frequency in C. dalmanni. In order to investigate trade-offs that might constrain male mating frequency under natural conditions we examined correlated responses to artificial selection. We measured accessory gland length, testis length and eyespan after 7 and 14 generations of selection. High line males had significantly larger accessory glands than low line males. No consistent correlated responses to selection were found in testis length or eyespan. Our results suggest that costs associated with the production and maintenance of large accessory glands, although yet to be identified, are likely to be a major constraint on mating frequency in natural populations of C. dalmanni.

Predicting the outcome of cholinesterase inhibitor treatment in Alzheimer's disease.

OBJECTIVE: To investigate the possibility that response to cholinesterase inhibitor therapy could be predicted by easily measurable variables that are known to change as a result of treatment (such as the Mini Mental State Examination), measures of function (such as the instrumental activities of daily living and the social behaviour subscales of the Nurse's Observation Scale for Geriatric Patients), and measures of attention (such as the Digit Symbol Substitution Test; DSST), or that might influence response through structural (for example, age, cerebrovascular disease, medial temporal lobe (MTL) atrophy, hypertension) or chemical (for example, smoking) mechanisms. METHOD: This was a cohort study of 160 consecutive outpatients with probable Alzheimer's disease who commenced cholinesterase inhibitor treatment over a 3 year period in a semi-rural area of Scotland. RESULTS: The overall response rate was 42.1%. Stratification of response between good and poor responders was possible using baseline DSST and a measure of MTL thickness using CT. Among the patients, 60.4% of those above the cut off point for both DSST and MTL thickness (29/48 subjects) were classified as good responders, compared with 6.3% of subjects below the cut off point for both (1/16 subjects). Subjects above the cut off point for both measures were more likely to be classified as good responders than subjects with only one or no values above the respective cut off points (chi(2) = 10.61, df = 1, p = 0.001) CONCLUSIONS: The DSST and a measure of MTL thickness derived from CT scanning may be useful in improving the prediction of response to cholinesterase inhibitors in subjects with AD. Subjects with low DSST scores and more severe MTL atrophy are unlikely to respond to treatment. These preliminary data justify a prospective trial of the usefulness of our suggested predictive measures.