High-dose femtosecond-scale gamma-ray beams for radiobiological applications.

Objective. In the irradiation of living tissue, the fundamental physical processes involved in radical production typically occur on a timescale of a few femtoseconds. A detailed understanding of these phenomena has thus far been limited by the relatively long duration of the radiation sources employed, extending well beyond the timescales for radical generation and evolution.Approach. Here, we propose a femtosecond-scale photon source, based on inverse Compton scattering of laser-plasma accelerated electron beams in the field of a second scattering laser pulse.Main results. Detailed numerical modelling indicates that existing laser facilities can provide ultra-short and high-flux MeV-scale photon beams, able to deposit doses tuneable from a fraction of Gy up to a few Gy per pulse, resulting in dose rates exceeding 1013Gy/s.Significance. We envisage that such a source will represent a unique tool for time-resolved radiobiological experiments, with the prospect of further advancing radio-therapeutic techniques.

Enhanced thromboprophylaxis in critically ill patients with COVID-19 infection.

Background: Patients with severe SARS-CoV-2 infection have been shown to have abnormal coagulation parameters and are at increased risk of thromboembolism. The optimal thromboprophylaxis regimen that minimizes thrombosis without increased risk of serious bleeding is uncertain. Objectives: To describe the efficacy and safety of increased intensity (enhanced) thromboprophylaxis in patients with COVID-19 admitted to the medical intensive care unit (MICU). Methods: This is a retrospective cohort analysis of patients with a diagnosis of COVID-19 admitted to the MICU of an urban safety net hospital. With the exception of patients being supported with extracorporeal membrane oxygenation or on chronic anticoagulation who received therapeutic dosing of anticoagulation, thromboprophylaxis was given as either enoxaparin or unfractionated heparin in doses higher than those recommended for standard prophylaxis, but lower than those used for therapeutic anticoagulation. Main results: Of the 120 patients managed with an enhanced thromboprophylaxis protocol, 6 (5%) experienced thromboembolism as a result of their COVID-19 disease (1 pulmonary embolus, 4 deep vein thromboses, and 1 arterial embolism). Four patients experienced major bleeding while receiving therapeutic anticoagulation. Conclusions: In critically ill patients with COVID-19, increased intensity (enhanced) thromboprophylaxis appears to be effective at preventing clinically significant thromboembolic events without an increased risk of serious bleeding.

Comparison of water-based foam and carbon dioxide gas emergency depopulation methods of turkeys.

Recommended response strategies for outbreaks of avian influenza and other highly contagious poultry diseases include surveillance, quarantine, depopulation, disposal, and decontamination. The best methods of emergency mass depopulation should maximize human health and safety while minimizing disease spread and animal welfare concerns. The goal of this project was to evaluate the effectiveness of 2 mass depopulation methods on adult tom turkeys. The methods tested were carbon dioxide gassing and water-based foam. The time to unconsciousness, motion cessation, brain death, and altered terminal cardiac activity were recorded for each bird through the use of an electroencephalogram, accelerometer, and electrocardiogram. Critical times for physiological events were extracted from sensor data and compiled in a spreadsheet for statistical analysis. A statistically significant difference was observed in time to brain death, with water-based foam resulting in faster brain death (µ = 190 s) than CO2 gas (µ = 242 s). Though not statistically significant, differences were found comparing the time to unconsciousness (foam: µ = 64 s; CO2 gas: µ = 90 s), motion cessation (foam: µ = 182 s; CO2 gas: µ = 153 s), and altered terminal cardiac activity (foam: µ = 208 s; CO2 gas µ = 242 s) between foam and CO2 depopulation treatments. The results of this study demonstrate that water-based foam can be used to effectively depopulate market size male turkeys.

Evaluation of EEG based determination of unconsciousness vs. loss of posture in broilers.

Evaluation of the loss of consciousness in poultry is an essential component in evaluating bird welfare under a variety of situations and applications. Many current approaches to evaluating loss of consciousness are qualitative and require observation of the bird. This study outlines a quantitative method for determining the point at which a bird loses consciousness. In this study, commercial broilers were individually anesthetized and the brain activity recorded as the bird became unconscious. A wireless EEG transmitter was surgically implanted and the bird anesthetized after a 24-48 h recovery. Each bird was monitored during treatment with isoflurane anesthesia and EEG data was evaluated using a frequency based approach. The alpha/delta (A/D) ratio and loss of posture (LOP) were used to determine the point at which the birds went unconscious. There was no statistically significant difference between time to unconsciousness as measured by A/D ratio or LOP.

Electroencephalogram-based methodology for determining unconsciousness during depopulation.

When an avian influenza or virulent Newcastle disease outbreak occurs within commercial poultry, key steps involved in managing a fast-moving poultry disease can include: education; biosecurity; diagnostics and surveillance; quarantine; elimination of infected poultry through depopulation or culling, disposal, and disinfection; and decreasing host susceptibility. Available mass emergency depopulation procedures include whole-house gassing, partial-house gassing, containerized gassing, and water-based foam. To evaluate potential depopulation methods, it is often necessary to determine the time to the loss of consciousness (LOC) in poultry. Many current approaches to evaluating LOC are qualitative and require visual observation of the birds. This study outlines an electroencephalogram (EEG) frequency domain-based approach for determining the point at which a bird loses consciousness. In this study, commercial broilers were used to develop the methodology, and the methodology was validated with layer hens. In total, 42 data sets from 13 broilers aged 5-10 wk and 12 data sets from four spent hens (age greater than 1 yr) were collected and analyzed. A wireless EEG transmitter was surgically implanted, and each bird was monitored during individual treatment with isoflurane anesthesia. EEG data were evaluated using a frequency-based approach. The alpha/delta (A/D, alpha: 8-12 Hz, delta: 0.5-4 Hz) ratio and loss of posture (LOP) were used to determine the point at which the birds became unconscious. Unconsciousness, regardless of the method of induction, causes suppression in alpha and a rise in the delta frequency component, and this change is used to determine unconsciousness. There was no statistically significant difference between time to unconsciousness as measured by A/D ratio or LOP, and the A/D values were correlated at the times of unconsciousness. The correlation between LOP and A/D ratio indicates that the methodology is appropriate for determining unconsciousness. The A/D ratio approach is suitable for monitoring during anesthesia, during depopulation, and in situations where birds cannot be readily viewed.

Mass emergency water-based foam depopulation of poultry.

When an avian influenza or virulent Newcastle disease outbreak occurs within commercial poultry, a large number of birds that are infected or suspected of infection must be destroyed on site to prevent the rapid spread of disease. The choice of mass emergency depopulation procedures is limited, and all options have limitations. Water-based foam mass emergency depopulation of poultry was developed in 2006 and conditionally approved by the U.S. Department of Agriculture and American Veterinary Medical Association. Water-based foam causes mechanical hypoxia and can be used for broilers, layers, turkeys, and ducks. The time to physiologic states was evaluated for broilers, layer hens, turkeys, and ducks, comparing water-based foam and CO2 gas using electroencephalogram (unconsciousness and brain death), electrocardiogram (altered terminal cardiac activity), and accelerometer (motion cessation). In broilers, turkeys, and layer hens, water-based foam results in equivalent times to unconsciousness, terminal convulsions, and altered terminal cardiac activity. With Pekin ducks, however, CO2 gas resulted in shorter times to key physiologic states, in particular unconsciousness, altered terminal cardiac activity, motion cessation, and brain death.

Comparison of water-based foam and inert-gas mass emergency depopulation methods.

Current control strategies for avian influenza (AI) and other highly contagious poultry diseases include surveillance, quarantine, depopulation, disposal, and decontamination. Selection of the best method of emergency mass depopulation involves maximizing human health and safety while minimizing disease spread and animal welfare concerns. Proper selection must ensure that the method is compatible with the species, age, housing type, and disposal options. No one single method is appropriate for all situations. Gassing is one of the accepted methods for euthanatizing poultry. Whole-house, partial-house, or containerized gassing procedures are currently used. The use of water-based foam was developed for emergency mass depopulation and was conditionally approved by the United States Department of Agriculture in 2006. Research has been done comparing these different methods; parameters such as time to brain death, consistency of time to brain death, and pretreatment and posttreatment corticosterone stress levels were considered. In Europe, the use of foam with carbon dioxide is preferred over conventional water-based foam. A recent experiment comparing CO2 gas, foam with CO2 gas, and foam without CO2 gas depopulation methods was conducted with the use of electroencephalometry results. Foam was as consistent as CO2 gassing and more consistent than argon-CO2 gassing. There were no statistically significant differences between foam methods.

Postoutbreak disinfection of mobile equipment.

Current control strategies for avian influenza virus, exotic Newcastle disease, and other highly contagious poultry diseases include surveillance, quarantine, depopulation, disposal, and decontamination. Skid steer loaders and other mobile equipment are extensively used during depopulation and disposal. Movement of contaminated equipment has been implicated in the spread of disease in previous outbreaks. One approach to equipment decontamination is to power wash the equipment, treat with a liquid disinfectant, change any removable filters, and let it sit idle for several days. In this project, multiple disinfectant strategies were individually evaluated for their effectiveness at inactivating Newcastle disease virus (NDV) on mechanical equipment seeded with the virus. A small gasoline engine was used to simulate typical mechanical equipment. A high titer of LaSota strain, NDV was applied and dried onto a series of metal coupons. The coupons were then placed on both interior and exterior surfaces of the engine. Liquid disinfectants that had been effective in the laboratory were not as effective at disinfecting the engine under field conditions. Indirect thermal fog showed a decrease in overall virus titer or strength. Direct thermal fog was more effective than liquid spray application or indirect thermal fog application.

Review of the carriage of zoonotic bacteria by arthropods, with special reference to Salmonella in mites, flies and litter beetles.

This systematic review considers the relationship between arthropods commonly found in and around livestock premises and zoonotic bacteria. The principal focus is upon insects and arachnids on poultry units, where houses, litter and manure provide good conditions for the growth, multiplication and protection of flies, beetles and mites, and where zoonotic pathogens such as Salmonella and Campylobacter are prevalent. Other members of the Enterobacteriaceae and the taxa Clostridium, Helicobacter, Erysipelas and Chlamydiaceae are also discussed. Salmonella is widely distributed in the flies of affected livestock units and is detectable to a lesser degree in beetles and mites. Persistent carriage appears to be common and there is some field and experimental evidence to support arthropod-mediated transmission between poultry flocks, particularly carry-over from one flock to the next. Campylobacter may readily be isolated from arthropods in contact with affected poultry flocks, although carriage is short-lived. There appears to be a role for flies, at least, in the breaching of biosecurity around Campylobacter-negative flocks. The carriage of other zoonotic bacteria by arthropods has been documented, but the duration and significance of such associations remain uncertain in the context of livestock production.

Juvenile hormone regulation of male accessory gland activity in the red flour beetle, Tribolium castaneum.

Male accessory gland proteins (Acps) act as key modulators of reproductive success in insects by influencing the female reproductive physiology and behavior. We used custom microarrays and identified 112 genes that were highly expressed in male accessory glands (MAG) in the red flour beetle, Tribolium castaneum. Out of these 112 identified genes, 59 of them contained sequences coding for signal peptide and cleavage site and the remaining 53 contained transmembrane domains. The expression of 14 of these genes in the MAG but not in other tissues of male or female was confirmed by quantitative real-time PCR. In virgin males, juvenile hormone (JH) levels increased from second day post adult emergence (PAE), remained high on third day PAE and declined on fourth day PAE. The ecdysteroid titers were high soon after adult emergence but declined to minimal levels from 1 to 5 days PAE. Feeding of juvenile hormone analog, hydroprene, but not the ecdysteroid analog, RH-2485, showed an increase in size of MAGs, as well as an increase in total RNA and protein content of MAG. Hydroprene treatment also increased the expression of Acp genes in the MAG. RNAi-mediated knock-down in the expression of JHAMT gene decreased the size of MAGs and expression of Acps. JH deficiency influenced male reproductive fitness as evidenced by a less vigor in mating behavior, poor sperm transfer, low egg and the progeny production by females mated with the JH deficient males. These data suggest a critical role for JH in the regulation of male reproduction especially through MAG secretions.

Effects on climacteric symptoms, bone and lipoprotein metabolism of hormone replacement therapy delivered by estradiol-releasing intravaginal rings: a pilot study.

OBJECTIVE: To assess the efficacy and tolerability of intravaginal rings (IVRs) delivering estradiol. DESIGN: This was a dose-escalating, continuous-dosing, pilot study. METHODS: Sixteen women post surgical menopause were recruited at a hospital-based menopause clinic. Over 20 weeks, each patient had IVR devices releasing 50, 75, 100, 150 and 200 mug/day of estradiol inserted consecutively at 4-weekly intervals. MAIN OUTCOME MEASURES: Climacteric symptoms were assessed, and levels of serum estradiol, lipoproteins and biochemical indices of bone turnover were estimated prior to insertion of the first IVR and at each monthly visit, when the IVR was changed to one of a higher dose. The susceptibility of low-density lipoprotein (LDL) to oxidation was assessed at 0, 12 and 20 weeks. RESULTS: Twelve women completed the study. The rings were well tolerated and serum estradiol levels increased in parallel with each increasing dose. Vasomotor and psychological symptoms and loss of libido were reduced by 76% (p < 0.001), 44% (p < 0.001) and 44% (p < 0.05), respectively, by the end of the study. There were no significant changes in levels of serum lipoproteins, although the ratio of LDL cholesterol to high-density lipoprotein cholesterol decreased by 7.2% (p = 0.01) after 20 weeks. The susceptibility of LDL to oxidation did not change. Urinary excretion of both calcium and deoxypyridinoline cross-links decreased significantly (p < 0.001), indicating a reduction in bone resorption. CONCLUSIONS: The rings were effective in controlling climacteric symptoms and had beneficial effects on bone metabolism, but no significant effects on lipoprotein levels or the susceptibility of LDL to oxidation.

National plastic surgery survey: brow lifting techniques and complications.

The purpose of this survey was to assess trends in brow lifting philosophy, techniques, and complications. This is the second of a three-part survey; the first part reported on complications with face lift techniques, and the final report will address practice management issues, including facility and ancillary procedures. Surveys were sent to 3800 members of the American Society of Plastic Surgeons; the response rate was 15 percent. This survey represents data on 6951 brow lifts, of which approximately 50 percent were performed endoscopically and 50 percent with a coronal incision. Several conclusions about the practice of the respondents were reached: (1) Both brow lift techniques were considered to be effective. (2) Surgeons considered coronal brow lifting to be more effective for the three basic goals of brow lifting: brow elevation, reduction of transverse lines, and reduction of glabellar lines. (3) Reported complication rates for both techniques were low, and the most frequent complication was alopecia (varying from 2.9 percent to 4 percent). (4) Patient satisfaction varied from 98.2 percent to 99.2 percent. (5) Major complications were rarely reported.

Tryptophan depletion in SSRI-recovered depressed outpatients.

RATIONALE: Recently, a number of studies have challenged the finding that acute tryptophan depletion (TD) increases depressive symptoms in medicated, formerly depressed patients. The present study examined the effects of acute nutritional TD on remitted depressed patients currently treated with selective serotonin reuptake inhibitors. In an attempt to clarify conflicting earlier findings, the effects of a number of clinical variables on outcome were also investigated. METHODS: Ten patients underwent TD in a double-blind, controlled, balanced crossover fashion. The control session followed the procedure of Krahn et al. (1996 Neuropsychopharmacology 15:325-328). Sessions were 5-8 days apart. RESULTS: TD was significantly related to increased scores on clinician-rated depression and anxiety scales, and on self-rated depression, anxiety, and somatic symptoms. The control challenge had no effect, despite the fact that the reductions in plasma tryptophan during the control session were unexpectedly high. Some evidence was found for a threshold in the relationship between reduction of plasma tryptophan and mood response. CONCLUSIONS: The mood effect of TD in medicated, formerly depressed patients was confirmed. A threshold may exist for mood effects following TD, implying that recent negative findings may have been caused by insufficient depletion. No other predicting or mediating factors were identified, although the variable "history of response pattern to medication" deserves further study.

National plastic surgery survey: face lift techniques and complications.

The purpose of this study was to assess trends in technique and philosophy of face lifting, associated procedures, and the incidence and management of complications. Surveys were sent to 3800 members of the American Society of Plastic and Reconstructive Surgeons (ASPRS); 570 surveys (15 percent) were returned. Numerous very specific technique and philosophy questions were asked. Details of demographics, techniques, incidence of complications, management of complications, and basic philosophy are presented. Three basic conclusions can be gleaned from this study: (1) Surgeons perform more tried and true methods of aesthetic surgery, rather than the many new methods that seem to get the most attention in the media and at the meetings. (2) It seems that less-experienced surgeons tend to be generally more conservative in their approach to aesthetic surgery. (3) Complication rates reported by the plastic surgery community at large coincide with previous complication rates, as outlined in other nonsurvey studies. The authors expect to report additional data from the survey--on brow surgery (part II) and facility and ancillary procedures (part III)--in forthcoming publications.

Pramipexole augmentation in the treatment of unipolar and bipolar depression: a retrospective chart review.

OBJECTIVE: To assess the effectiveness and safety of pramipexole as an adjunctive medication in refractory bipolar and unipolar depression in a naturalistic setting. METHODS: Retrospective chart review by psychiatrists on staff at a university hospital identified all patients who had received pramipexole. Response was based on moderate to marked improvement in the Clinical Global Impression-Improvement (CGI-I) scale. RESULTS: Pramipexole (mean dose 0.70 mg/d, mean duration 24.4 weeks) was effective in 6/12 (50.0%) of patients with bipolar depression, and 8/20 (40%) of patients with unipolar depression, mean duration of follow-up of 24.4 weeks. One case of transient hypomania was noted. Eight patients discontinued pramipexole due to lack of response and four due to side effects. CONCLUSIONS: Pramipexole, used as an adjunct to antidepressants or mood stabilizers, appeared to be effective and safe in the treatment of unipolar and bipolar depression. These uncontrolled, retrospective, naturalistic pilot data require confirmation by controlled research before conclusions can be made.

Anxiety disorders in major depression.

The prevalence and clinical impact of anxiety disorder comorbidity in major depression were studied in 255 depressed adult outpatients consecutively enrolled in our Depression Research Program. Comorbid anxiety disorder diagnoses were present in 50.6% of these patients and included social phobia (27.0%), simple phobia (16.9%), panic disorder (14.5%), generalized anxiety disorder ([GAD] 10.6%), obsessive-compulsive disorder ([OCD] 6.3%), and agoraphobia (5.5%). While both social phobia and generalized anxiety preceded the first episode of major depression in 65% and 63% of cases, respectively, panic disorder (21.6%) and agoraphobia (14.3%) were much less likely to precede the first episode of major depression than to emerge subsequently. Although comorbid groups were not distinguished by depression, anxiety, hostility, or somatic symptom scores at the time of study presentation, patients with comorbid anxiety disorders tended to be younger during the index episode and to have an earlier onset of the major depressive disorder (MDD) than patients with major depression alone. Our results support the distinction between anxiety symptoms secondary to depression and anxiety disorders comorbid with major depression, and provide further evidence for different temporal relationships with major depression among the several comorbid anxiety disorders.

Haemochromatosis: work and social implications.

Hereditary haemochromatosis is prevalent in our society and requires vigorous and lifelong treatment. Diagnosis of the disorder may be delayed or missed due to its nonspecific symptoms and diverse manifestations. This can have lifelong consequences for the sufferer. Early diagnosis prevents severe organ damage and premature death and leads to a normal productive life. Screening family members will enable early diagnosis of those with the HFE gene mutation. The stigma attached to having a genetic condition may have consequences for job opportunities and for life and health insurance. Education of the community (including workplaces and employers) as well as health service providers will not only increase the likelihood of early diagnosis of haemochromatosis but will ease the social consequences of suffering from this disorder.