Museum records indicate male bias in pollinators of sexually deceptive orchids.

Deception has evolved in a range of taxa. When deception imposes costs, yet persists over generations, exploited species typically have traits to help them bear or minimise costs. The sexually deceptive orchids, Cryptostylis spp., are pollinated by tricking male haplodiploid wasps (Lissopimpla excelsa) into mating with flowers, which offer no reward and often elicit sperm wastage. We hypothesise that by attracting haplodiploid species, orchids have a pollinator ideally suited to withstand the costs of sexual deception-and a selective advantage compared to other orchids. Haplodiploid females can reproduce with or without sperm-albeit when spermless, females can only have sons. Through orchid deception and sperm wastage, deceived haplodiploid populations could become male biased, providing enough males to share between orchids and females. In this way, pollinator populations can persist despite high densities of sexually deceptive orchids. Here, we aim to broadly test this prediction using museum and digital records of the pollinator, L. excelsa, from sites with or without orchids. For robustness, we also analyse the sex ratio of a sister ichneumonid species that occurs in the same areas but is not deceived by orchids. We found that at sites with orchids, L. excelsa was significantly more male biased than at sites without orchids and significantly more male biased than the sister ichneumonid. This survey is the first to test the population-level effects of sexually deceptive orchids on their pollinator. It supports our prediction that orchid deception can drive male-biased sex ratios in exploited pollinators.

Female fecundity and offspring survival are not increased through sexual cannibalism in the spider Larinioides sclopetarius.

Many hypotheses explaining the evolution and maintenance of sexual cannibalism incorporate the nutritional aspect of the consumption of males. Most studies have focused on a fecundity advantage through consumption of a male; however, recent studies have raised the intriguing possibility that consumption of a male may also affect offspring quality. In particular, recent studies suggest prolonged survival for offspring from sexually cannibalistic females. Here, we measured the protein and lipid content of males compared to insect prey (crickets), quantified female nutrient intake of both prey types and finally assessed how sexual cannibalism affects female fecundity and spiderling quality in the orb-web spider Larinioides sclopetarius. We found no evidence that sexual cannibalism increased fecundity when compared to a female control group fed a cricket. Contrary to previous studies, spiderlings from females fed a male showed reduced survival under food deprivation compared to spiderlings from the control group. Offspring from females fed a male also tended to begin web construction sooner. The low lipid content of males compared to crickets may have reduced offspring survival duration. Whether additional proteins obtained through consumption of a male translate to enhanced silk production in offspring requires further investigation.

Potential drug-drug and drug-disease interactions in well-functioning community-dwelling older adults.

WHAT IS KNOWN AND OBJECTIVE: There are few studies examining both drug-drug and drug-disease interactions in older adults. Therefore, the objective of this study was to describe the prevalence of potential drug-drug and drug-disease interactions and associated factors in community-dwelling older adults. METHODS: This cross-sectional study included 3055 adults aged 70-79 without mobility limitations at their baseline visit in the Health Aging and Body Composition Study conducted in the communities of Pittsburgh PA and Memphis TN, USA. The outcome factors were potential drug-drug and drug-disease interactions as per the application of explicit criteria drawn from a number of sources to self-reported prescription and non-prescription medication use. RESULTS: Over one-third of participants had at least one type of interaction. Approximately one quarter (25·1%) had evidence of had one or more drug-drug interactions. Nearly 10·7% of the participants had a drug-drug interaction that involved a non-prescription medication. % The most common drug-drug interaction was non-steroidal anti-inflammatory drugs (NSAIDs) affecting antihypertensives. Additionally, 16·0% had a potential drug-disease interaction with 3·7% participants having one involving non-prescription medications. The most common drug-disease interaction was aspirin/NSAID use in those with history of peptic ulcer disease without gastroprotection. Over one-third (34·0%) had at least one type of drug interaction. Each prescription medication increased the odds of having at least one type of drug interaction by 35-40% [drug-drug interaction adjusted odds ratio (AOR) = 1·35, 95% confidence interval (CI) = 1·27-1·42; drug-disease interaction AOR = 1·30; CI = 1·21-1·40; and both AOR = 1·45; CI = 1·34-1·57]. A prior hospitalization increased the odds of having at least one type of drug interaction by 49-84% compared with those not hospitalized (drug-drug interaction AOR = 1·49, 95% CI = 1·11-2·01; drug-disease interaction AOR = 1·69, CI = 1·15-2·49; and both AOR = 1·84, CI = 1·20-2·84). WHAT IS NEW AND CONCLUSION: Drug interactions are common among community-dwelling older adults and are associated with the number of medications and hospitalization in the previous year. Longitudinal studies are needed to evaluate the impact of drug interactions on health-related outcomes.

Evaluation of watershed-derived mass loads to prioritize TMDL decision-making.

A total maximum daily load (TMDL) for oxygen demanding substances is being implemented in the San Joaquin River (SJR) in California (USA) due to frequently occurring low dissolved oxygen conditions. The SJR is a eutrophic river, heavily impacted by agriculture. A mass balance was developed to identify the sources of oxygen-demanding substances and nutrients to the river with the objective of providing a scientific basis for management actions needed to meet TMDL requirements. Data were collected for flow and water quality and mass loads calculated for sites within the main stem of the SJR, river inputs (tributaries), and diversions in the study area. Using a quadrant analysis, tributary flows and loads are ranked to identify targets for water quality improvement efforts. Additionally, all mass loads were summed (inputs minus diversions) and compared with observed loads at the downstream limit of the study area. The mass balance analysis identifies major contributors of mass loads and mass balance closure is assessed for each constituent. These analysis methods inform the TMDL process which includes a load allocation, and is useful for determining locations for implementation of improvement projects needed to improve the health of the river.

Effect of sleep deprivation on labour epidural catheter placement.

BACKGROUND: Epidural catheter insertion for labour analgesia is an invasive procedure with potential serious complications, often performed by a sleep-deprived clinician. The aim of this study was to examine the effects of sleep deprivation on physicians of variable levels of experience performing this procedural skill in the clinical setting. METHODS: After institutional review board approval, anaesthetists of three levels of experience were recruited: novice residents (<30 epidurals, n=9), experienced residents (>100 epidurals, n=8), and attending anaesthetists (>500 epidurals, n=12). All participants were measured twice, rested and sleep deprived in a random order while performing a labour epidural for analgesia. Our primary outcome measures were scores achieved on the Imperial College Surgical Assessment Device (ICSAD) (measuring path length, number of movements, and time), task-specific checklist (CL), and global rating scale (GRS). Sleep deprivation was documented by the ActiGraph and Epworth sleepiness scale. RESULTS: Subjects were adequately sleep deprived for their sleep deprivation observation. Data were analysed with a two-way mixed design analysis of variance. No significant difference in the effect of sleep deprivation on performance was detected between the groups on the ICSAD measures of movement (P=0.86), path length (P=0.79), and time (P=0.80), or for the CL (P=0.65), and GRS (P=0.86). CONCLUSIONS: The performance of this procedural skill in a clinical setting does not seem to be affected by sleep deprivation irrespective of the level of experience.

Operant control of occipital theta rhythm affects performance in a radar monitoring task.

Detection efficiency of human observers deteriorates rapidly in monotonous monitoring tasks; this effect (the vigilance decrement) has been associated with increased theta band activity in the electroencephalogram. Suppression of theta activity by operant methods enhances monitoring efficiency, whereas theta augmentation further degrades task performance. These results demonstrate a lawful relationship between operantly regulated cortical activity and behavior in man.

Diazepam impairs lateral position control in highway driving.

Nine expert drivers operated an instrumented vehicle in tests over a highway at night after being treated with diazepam (5 and 10 milligrams), a placebo, and nothing. They reacted to 10 milligrams of diazepam with increased lateral position variability. Potentially dangerous impairment was inferred from the reactions of some subjects.

Pharmacological and clinical aspects of antiepileptic drug use in the elderly.

In this article, epidemiological and clinical aspects related to the use of antiepileptic drugs (AEDs) in the elderly are highlighted. Studies have shown that people with epilepsy receiving AED treatment show important deficits in physical and social functioning compared with age-matched people without epilepsy. To what extent these deficits can be ascribed to epilepsy per se or to the consequences of AED treatment remains to be clarified. The importance of characterizing the effects of AEDs in an elderly population is highlighted by epidemiological surveys indicating that the prevalence of AED use is increased in elderly people, particularly in those living in nursing homes. Both the pharmacokinetics and the pharmacodynamics of AEDs may be altered in old age, which may contribute to the observation that AEDs are among the drug classes most commonly implicated as causing adverse drug reactions in an aged population. Age alone is one of several contributors to alterations in AED response in the elderly; other factors include physical frailty, co-morbidities, dietary influences, and drug interactions. Individualization of dosage, avoidance of unnecessary polypharmacy, and careful observation of clinical response are essential for an effective and safe utilization of AEDs in an elderly population.

Phase I trial of piritrexim capsules using prolonged, low-dose oral administration for the treatment of advanced malignancies.

A phase I trial of piritrexim was conducted by use of a prolonged, low-dose oral schedule. A number of different regimens were tested, including daily dosing for 21 days followed by 7 days of no drug therapy; continuous dosing; and daily dosing for 5 of 7 days for 3 consecutive weeks followed by a week of rest. Dose escalation was accomplished by increasing the dosing frequency from once a day to twice a day and then to three times a day and by increasing the number of days of administration. Fifty-one patients with advanced cancer were entered in the study. One hundred twenty-four (96%) of 129 courses were considered assessable. Myelosuppression proved to be the dose-limiting toxic effect. Other toxic effects included stomatitis, nausea and vomiting, anorexia, diarrhea, skin rash, fatigue, and elevation of liver transaminase levels. Antitumor activity was observed in patients with melanoma and bladder cancer, and disease stabilization occurred in those with sarcoma and pheochromocytoma. The recommended dosing schedule for phase II clinical trials is 25 mg three times a day for 5 days for 3 consecutive weeks followed by 1 week of no drug therapy.

Correlation of antitumor chemoimmunotherapy with serum inhibition of tumor cell destruction.

The administration of cyclophosphamide and Corynebacterium parvum in combination results in tumor growth inhibition greater than that resulting from the use of either agent alone. The precise mechanism(s) by which this chemoimmunotherapy combination results in a synergistic inhibiting effect is not known. The possibility was entertained that the tumor effect might be related to a greater decrease in serum-mediated interference with cellular cytotoxicity, i.e., "blocking" activity, by both agents in combination rather than by either alone. The present findings fail to support such an explanation. C. parvum by itself failed to decrease serum inhibition and in conjunction with cyclophosphamide resulted in an effect that was no greater than that produced by cyclophosphamide alone.

Phase II trial of piritrexim in metastatic melanoma using intermittent, low-dose administration.

A phase II trial of piritrexim (2,4-diamino-6[2,5-dimethoxybenzyl]-5-methyl pyrido-[2,3d] pyrimidine, 301U74; PTX) was conducted for patients with metastatic malignant melanoma using an intermittent, low-dose oral administration schedule. PTX was administered at a starting dose of 25 mg orally three times per day for 5 days weekly for 3 weeks followed by 1 week of rest. Thirty-one patients were entered onto the study. Among 31 patients assessable for response, there were two complete responses (CRs) and five partial responses (PRs) for a response rate (CR plus PR) of 23% (95% confidence limit, 10% to 42%). Five responses occurred in soft tissue lesions, and two responses occurred in lung lesions. The initial dose schedule was well tolerated. The dose-limiting toxicity was myelosuppression. PTX administered in this schedule appears to be active against malignant melanoma. Further clinical trials to confirm these results are underway.

Hemodynamic responses to combined therapy with captopril and hydralazine in patients with severe heart failure.

The hemodynamic benefits and safety of combined therapy with captopril and hydralazine were studied during invasive hemodynamic monitoring in 14 patients with severe heart failure. In eight patients, the individual effects of both drugs were evaluated before the administration of combined therapy, whereas hydralazine was added to maintenance captopril therapy in the other six patients. In the first group, captopril alone produced a marked decrease in pulmonary wedge pressure (28 +/- 4 to 18 +/- 5 mm Hg) and mean arterial pressure (85 +/- 20 to 69 +/- 13 mm Hg) (both p less than 0.001) without a significant increase in cardiac index. Hydralazine alone produced a marked increase in cardiac index (1.6 +/- 0.4 to 2.7 +/- 0.5 liters/min per m2) (p less than 0.001), but with a minimal decrease in pulmonary wedge pressure (28 +/- 4 to 23 +/- 4 mm Hg) (p less than 0.05) and without a significant change in mean arterial pressure. The combination of captopril and hydralazine produced an increase in cardiac index similar to that of hydralazine alone and decreases in pulmonary wedge pressure and mean arterial pressure similar to those with captopril alone. Most important, when hydralazine was added to captopril in the entire group of 14 patients, cardiac index increased markedly with little additional decrease in mean arterial pressure and no significant increase in heart rate. The one patient who experienced symptomatic hypotension with combination therapy also had dizziness with captopril alone. Seven of the nine patients maintained on long-term treatment experienced symptomatic improvement. Thus, in patients with severe chronic heart failure, the combined use of captopril and hydralazine is feasible and produces acute hemodynamic improvement superior to that from either drug alone.

A randomized trial of transfer for primary angioplasty versus on-site thrombolysis in patients with high-risk myocardial infarction: the Air Primary Angioplasty in Myocardial Infarction study.

OBJECTIVES: The Air Primary Angioplasty in Myocardial Infarction (PAMI) study was designed to determine the best reperfusion strategy for patients with high-risk acute myocardial infarction (AMI) at hospitals without percutaneous transluminal coronary angioplasty (PTCA) capability. BACKGROUND: Previous studies have suggested that high-risk patients have better outcomes with primary PTCA than with thrombolytic therapy. It is unknown whether this advantage would be lost if the patient had to be transferred for PTCA, and reperfusion was delayed. METHODS: Patients with high-risk AMI (age >70 years, anterior MI, Killip class II/III, heart rate >100 beats/min or systolic BP <100 mm Hg) who were eligible for thrombolytic therapy were randomized to either transfer for primary PTCA or on-site thrombolysis. RESULTS: One hundred thirty-eight patients were randomized before the study ended (71 to transfer for PTCA and 67 to thrombolysis). The time from arrival to treatment was delayed in the transfer group (155 vs. 51 min, p < 0.0001), largely due to the initiation of transfer (43 min) and transport time (26 min). Patients randomized to transfer had a reduced hospital stay (6.1 +/- 4.3 vs. 7.5 +/- 4.3 days, p = 0.015) and less ischemia (12.7% vs. 31.8%, p = 0.007). At 30 days, a 38% reduction in major adverse cardiac events was observed for the transfer group; however, because of the inability to recruit the necessary sample size, this did not achieve statistical significance (8.4% vs. 13.6%, p = 0.331). CONCLUSIONS: Patients with high-risk AMI at hospitals without a catheterization laboratory may have an improved outcome when transferred for primary PTCA versus on-site thrombolysis; however, this will require further study. The marked delay in the transfer process suggests a role for triaging patients directly to specialized heart-attack centers.

Syncope and presyncope associated with probable adverse drug reactions.

The purpose of this study was to determine whether syncope and presyncope were associated with drug therapy in 70 patients referred to a tertiary care ambulatory clinic. Drug use information was obtained, validated, and classified by its potential to cause syncope and presyncope. Utilizing a standardized adverse drug reaction algorithm, nine (13%) of the 70 patients were rated as having probable drug-induced syncope and presyncope events. Overall, 12 medications were implicated. Patients with probable adverse drug reactions were older, and taking more medications, or taking an antihypertensive. Seven of the nine patients with probable adverse drug reactions were previously classified as having syncope of unknown origin after their initial clinic evaluation. Syncope and presyncope are commonly associated with adverse drug reactions, especially in the elderly and those taking multiple medications.

Adverse events after discontinuing medications in elderly outpatients.

BACKGROUND: Discontinuation of drug therapy is an important intervention in elderly outpatients receiving multiple medications, but it may be associated with adverse drug withdrawal events (ADWEs). OBJECTIVE: To determine the frequency, types, timing, severity, and factors associated with ADWEs after discontinuing medications in elderly outpatients. PATIENTS: One hundred twenty-four ambulatory elderly participants in 1-year health service intervention trial at the Durham Veterans Affairs General Medicine Clinic in Durham, NC, who stopped taking medications. METHODS: A geriatrician retrospectively reviewed computerized medication records and clinical charts to determine medications no longer being taken and adverse events in the subsequent 4-month period. Possible ADWEs, determined by using the Naranjo causality algorithm, were categorized by therapeutic class, organ system, and severity. RESULTS: Of 238 drugs stopped, 62 (26%) resulted in 72 ADWEs among 38 patients. Cardiovascular (42%) and central nervous system (18%) drug classes were most frequently associated with ADWEs. The ADWEs most commonly involved the circulatory (51%) and central nervous (13%) systems, and 88% were attributed to exacerbations of underlying disease. Twenty-six ADWEs (36%) resulted in hospitalization or an emergency department or urgent care clinic visit. Only the number of medications stopped was associated with ADWE occurrence (adjusted odds ratio, 1.89; 95% confidence interval, 1.33-2.67). CONCLUSIONS: Most medications can be stopped in elderly outpatients without an ADWE occurrence. However, when ADWEs occur they resulted in substantial health care utilization. Practitioners should strive to discontinue drug therapy in the elderly but be vigilant for disease recurrence.

Kilovoltage radiosurgery with gold nanoparticles for neovascular age-related macular degeneration (AMD): a Monte Carlo evaluation.

This work uses Monte Carlo radiation transport simulation to assess the potential benefits of gold nanoparticles (AuNP) in the treatment of neovascular age-related macular degeneration with stereotactic radiosurgery. Clinically, a 100 kVp x-ray beam of 4 mm diameter is aimed at the macula to deliver an ablative dose in a single fraction. In the transport model, AuNP accumulated at the bottom of the macula are targeted with a source representative of the clinical beam in order to provide enhanced dose to the diseased macular endothelial cells. It is observed that, because of the AuNP, the dose to the endothelial cells can be significantly enhanced, allowing for greater sparing of optic nerve, retina and other neighboring healthy tissue. For 20 nm diameter AuNP concentration of 32 mg g(-1), which has been shown to be achievable in vivo, a dose enhancement ratio (DER) of 1.97 was found to be possible, which could potentially be increased through appropriate optimization of beam quality and/or AuNP targeting. A significant enhancement in dose is seen in the vicinity of the AuNP layer within 30 µm, peaked at the AuNP-tissue interface. Different angular tilting of the 4 mm beam results in a similar enhancement. The DER inside and in the penumbra of the 4 mm irradiation-field are almost the same while the actual delivered dose is more than one order of magnitude lower outside the field leading to normal tissue sparing. The prescribed dose to macular endothelial cells can be delivered using almost half of the radiation allowing reduction of dose to the neighboring organs such as retina/optic nerve by 49% when compared to a treatment without AuNP.

Evaluation of PCR and ELISA assays for screening clinical trial subjects for replication-competent retrovirus.

Gene delivery via murine-based recombinant retroviral vectors is currently widely used in gene therapy clinical trials. The vectors are engineered to be replication defective by replacing the structural and nonstructural genes of a cloned infectious retrovirus with a therapeutic gene of interest. The retroviral particles are currently generated in packaging cell lines, which supply all retroviral proteins in trans. Recombination between short homologous regions of the retroviral vector and packaging cell line elements can theoretically generate replication-competent retrovirus (RCR) and hence the Food and Drug Administration (FDA) requires the monitoring of clinical trial subjects for the presence of RCR. Sensitive polymerase chain reaction (PCR) assays have been used for the detection of murine leukemia virus (MLV) nucleotide sequences in peripheral blood mononuclear cells (PBMCs). A novel serological enzyme-linked immunosorbent assay (ELISA) for the detection of anti-MLV specific immunoglobulin (Ig) has been developed to be used as an alternative to the PCR assay. Both assays were used to monitor human immunodeficiency virus (HIV)-positive clinical trial subjects who had received multiple injections of HIV-IT (V), a retroviral vector encoding HIV-1 IIIBenv/rev. Western blot analysis and an in vitro vector neutralization assay were used to characterize further a subset of serum samples tested by ELISA. Results show no evidence of RCR infection in clinical trial subjects. PCR and ELISA assays are discussed in terms of their advantages and limitations as routine screening assays for RCR. The PCR assay is our current choice for monitoring clinical trial subjects receiving direct administration of vector, and the ELISA is our choice for those receiving ex vivo treatment regimens.

Benzodiazepine use and cognitive function among community-dwelling elderly.

OBJECTIVE: To evaluate the relation between benzodiazepine use and cognitive function among community-dwelling elderly. METHODS: This prospective cohort study included 2765 self-reporting subjects from the Duke Established Populations for Epidemiologic Studies of the Elderly. The subjects were cognitively intact at baseline (1986-1987) and alive at follow-up data collection 3 years later. Cognitive function was assessed with the Short Portable Mental Status Questionnaire (unimpaired versus impaired and change in score) and on the basis of the number of errors on the individual domains of the Orientation-Memory-Concentration Test. Benzodiazepine use was determined during in-home interviews and classified by dose, half-life, and duration. Covariates included demographic characteristics, health status, and health behaviors. RESULTS: After control for covariates, current users of benzodiazepine made more errors on the memory test (beta coefficient, 0.35; 95% confidence interval [CI], 0.10 to 0.61) than nonusers. Further assessment of the negative effects on memory among current users suggested a dose response in which users taking the recommended or higher dose made more errors (beta coefficient, 0.57; 95% CI, 0.26 to 0.88) and a duration response in which long-term users made more errors (beta coefficient, 0.39; 95% CI, 0.05 to 0.73) than nonusers. Users of agents with long half-lives and users of agents with short half-lives both had increased memory impairment (beta coefficient, 0.32; 95% CI, 0.01 to 0.64 and beta coefficient, 0.38; 95% CI, 0.02 to 0.75, respectively) relative to nonusers. Previous benzodiazepine use was unrelated to memory problems, and current and previous benzodiazepine use was unrelated to level of cognitive functioning as measured with the other 4 tests. CONCLUSIONS: The results suggested that current benzodiazepine use, especially in recommended or higher doses, is associated with worse memory among community-dwelling elderly.

Marked differences in antidepressant use by race in an elderly community sample: 1986-1996.

OBJECTIVE: Prescriptions of antidepressant medications have increased significantly over the past 15 years across the life cycle. One overall correlate of medication use in older adults is race, with African Americans using fewer medications than whites. Given the frequency of depressive symptoms among elderly populations, as well as the increased potential for adverse side effects from antidepressants, the relative contribution of race in the use of antidepressants is critical for determining well-designed studies. The authors analyzed data from a community-based cohort of elders followed for 10 years to determine the association of race to the use of antidepressants between 1986 and 1996, with control for known correlates of depression in late life. METHOD: Information on antidepressant use and demographic and health characteristics were obtained from a stratified, probability-based sample of 4,162 elders (equally distributed between African American and white community-dwelling subjects) in the Piedmont region of North Carolina during four in-person interviews spanning 10 years. Descriptive statistics were calculated. Logistic regression was used for the final models. RESULTS: A total of 4.6% of whites and 2.3% of African Americans used antidepressants in 1986. Approximately 14.3% of whites and 5.0% of African Americans used antidepressants in 1996. In controlled analyses, the prevalence odds ratio for antidepressant use in whites, compared to African Americans, was 1. 76 in 1986 and 3.77 in 1996. CONCLUSIONS: African American elders are much less likely to take antidepressants, and the difference in use increased over the 10 years of the survey.

Calcium channel blockers and cancer.

PURPOSE: We sought to explore the relation that has been previously reported between calcium channel blockers and an increased risk of cancer. SUBJECTS AND METHODS: We followed 3,511 participants, age 65 years or older, in the Duke Established Populations for Epidemiologic Studies of the Elderly for up to 10 years. Information about use of medications was obtained at baseline and 3 and 6 years later. Information about hospitalization for cancer, or death from cancer, was obtained from Health Care Financing Administration data and death certificates. RESULTS: Of the 133 users of calcium channel blockers, 16 (12%) developed cancer, compared with 548 (16%) of 3,378 nonusers (hazard ratio = 0.9; 95% confidence interval, 0.5 to 1.5). Adjusting for baseline and time-dependent covariates, such as race, diabetes, or blood pressure, for dose or class of calcium channel blockers, or for length of follow-up, had no effect. CONCLUSIONS: Use of calcium channel blockers does not appear to be related to cancer risk. Earlier reports showing such a relation may have been the result of chance.