Novel Management Methods: Immunocontraception and Other Fertility Control Tools

Impacts of overabundant ungulate populations on human activities and conservation include crop and forestry losses, collisions with vehicles, disease transmission, nuisance behaviour, damage to infrastructures, predation on livestock and native species, and reduction of biodiversity in plant and animal communities (e.g. Curtis et ai., 2002; Massei et al., 2011; Reimoser and Putman, 2011; Ferroglio et ai., 2011; Langbein et al., 2011). Current trends in human population growth and landscape development indicate that human-ungulate conflicts in Europe, as well as in the United States, are likely to increase in parallel with increased expansion in numbers and range of many of these species (Rutberg and Naugle, 2008; Brainerd and Kaltenborn, 2010; Gionfriddo et aI., 2011 a). Many of these conflicts have been traditionally managed by lethal methods. However, current trends in distribution and numbers of wild boar, feral pigs and deer in Europe and in the United States (e.g. Saez-Royuela and Telleria, 1986; Waithman et ai., 1999; Ward, 2005; Apollonio et al., 2010) suggest that recreational hlllting is not sufficient to control ungulate densities. In addition, ethical considerations regarding humane treatment of animals are increasingly shaping public attitudes about what are considered acceptable methods of mitigating human-wildlife conflicts, and lethal control is often opposed (Beringer et al., 2002; Wilson, 2003; Barfield et al., 2006; McShea, 2012). Public antipathy towards lethal methods increasingly constrains the options available for ungulate management, particularly in urban and suburban areas and in protected areas where culling is often opposed on ethical, legal or safety grounds (Kirkpatrick et al., 2011; Boulanger et al., 2012; Rutberg et al., 2013). Consequently, interest in non-lethal methods, such as translocation or fertility control, has increased (Fagerstone et ai., 2010)

Predicting sleep disordered breathing in outpatients with suspected OSA

Objective To validate the utilities of Berlin, STOP and STOP-BANG Questionnaires, other patient characteristics, comorbidities, Epworth Sleepiness Scale (ESS), fractional exhaled nitric oxide (FENO) and blood markers for the prediction of sleep disordered breathing (SDB) on limited polygraphy. Setting North Glasgow Sleep Service (a tertiary referral centre). Participants 129 consecutive patients, aged ≥16 years, referred to the sleep clinic for assessment of possible obstructive sleep apnoea. Interventions We selected cut-points of apnoea hypopnoea index (AHI) of ≥5 and ≥15/h from their home polygraphy and determined associations of these with individual symptoms, questionnaire scores and other results. Receiver operating characteristic analysis and univariate and multivariate logistic regression were used to explore these. Primary and secondary outcomes measures Primary: The utility of STOP, STOP-BANG and Berlin Questionnaires for prediction of SDB. Secondary: The utility of other measures for prediction of SDB. Results AHI was ≥5 in 97 patients and ≥15 in 56 patients. STOP and STOP-BANG scores were associated with both AHI cut-points but results with ESS and Berlin Questionnaire scores were negative. STOP-BANG had a negative predictive value 1.00 (0.77–1.00) for an AHI ≥15 with a score ≥3 predicting AHI ≥5 with sensitivity 0.93 (95% CI 0.84 to 0.98) and accuracy 79%, while a score ≥6 predicted AHI ≥15 with specificity 0.78 (0.65 to 0.88) and accuracy 72%. Neck circumference ≥17 inch and presence of witnessed apnoeas were independent predictors of SDB. Conclusions STOP and STOP-BANG Questionnaires have utility for the prediction of SDB in the sleep clinic population. Modification of the STOP-BANG Questionnaire merits further study in this and other patient groups.</p

Obstructive Sleep Apnoea Syndrome and Weight Loss: Review

Obstructive sleep apnoea (OSA) syndrome is common, and obesity is a major risk factor. Increased peripharyngeal and central adiposity result in increased pharyngeal collapsibility, through increased mechanical loading around the upper airway, reduced tracheal traction on the pharynx, and reduced neuromuscular activity, particularly during sleep. Significant and sustained weight loss, if achieved, is likely to be a useful therapeutic option in the management of OSA and may be attempted by behavioural, pharmacological, and surgical approaches. Behavioural therapy programs that focus on aspects such as dietary intervention, exercise prescription patients and general lifestyle counselling have been tested. Bariatric surgery is an option in the severely obese when nonsurgical measures have failed, and laparoscopic adjustable gastric banding and Roux-en-Y gastric bypass are the most commonly employed techniques in the United Kingdom. Most evidence for efficacy of surgery comes from cohort studies. The role of sibutramine in OSA in the obese patients has been investigated, however, there are concerns regarding associated cardiovascular risk. In this paper the links between obesity and OSA are discussed, and the recent studies evaluating the behavioural, pharmacological and surgical approaches to weight loss in OSA are reviewed

Obesity, inflammation, and severe asthma: an update

Purpose of Review: Obesity-associated difficult asthma continues to be a substantial problem and, despite a move to address treatable traits affecting asthma morbidity and mortality, it remains poorly understood with limited phenotype-specific treatments. The complex association between asthma, obesity, and inflammation is highlighted and recent advances in treatment options explored. Recent Findings: Obesity negatively impacts asthma outcomes and has a causal link in the pathogenesis of adult-onset asthma. Imbalance in the adipose organ found in obesity favours a pro-inflammatory state both systemically and in airways. Obesity may impact currently available asthma biomarkers, and obesity-associated asthma specific biomarkers are needed. Whilst surgical weight loss interventions are associated with improvements in asthma control and quality of life, evidence for pragmatic conservative options are sparse. Innovative approaches tackling obesity-mediated airway inflammation may provide novel therapies. Summary: The immunopathological mechanisms underlying obesity-associated asthma require further research that may lead to novel therapeutic options for this disease. However, weight loss appears to be effective in improving asthma in this cohort and focus is also needed on non-surgical treatments applicable in the real-world setting

Biomarker-based asthma phenotypes of corticosteroid response

BackgroundAsthma is a heterogeneous disease with different phenotypes. Inhaled corticosteroid (ICS) therapy is a mainstay of treatment for asthma, but the clinical response to ICSs is variable.ObjectiveWe hypothesized that a panel of inflammatory biomarkers (ie, fraction of exhaled nitric oxide [Feno], sputum eosinophil count, and urinary bromotyrosine [BrTyr] level) might predict steroid responsiveness.MethodsThe original study from which this analysis originates comprised 2 phases: a steroid-naive phase 1 and a 28-day trial of ICSs (phase 2) during which Feno values, sputum eosinophil counts, and urinary BrTyr levels were measured. The response to ICSs was based on clinical improvements, including a 12% or greater increase in FEV1, a 0.5-point or greater decrease in Asthma Control Questionnaire score, and 2 doubling dose or greater increase in provocative concentration of adenosine 5′-monophosphate causing a 20% decrease in FEV1 (PC20AMP). Healthy control subjects were also evaluated in this study for comparison of biomarkers with those seen in asthmatic patients.ResultsAsthmatic patients had higher than normal Feno values, sputum eosinophil counts, and urinary BrTyr levels during the steroid-naive phase and after ICS therapy. After 28-day trial of ICSs, Feno values decreased in 82% of asthmatic patients, sputum eosinophil counts decreased in 60%, and urinary BrTyr levels decreased in 58%. Each of the biomarkers at the steroid-naive phase had utility for predicting steroid responsiveness, but the combination of high Feno values and high urinary BrTyr levels had the best power (13.3-fold, P < .01) to predict a favorable response to ICS therapy. However, the magnitude of the decrease in biomarker levels was unrelated to the magnitude of clinical response to ICS therapy.ConclusionA noninvasive panel of biomarkers in steroid-naive asthmatic patients predicts clinical responsiveness to ICS therapy

The Probable Detection of SN 1923A: The Oldest Radio Supernova?

Based upon the results of VLA observations, we report the detection of two unresolved radio sources that are coincident with the reported optical position of SN 1923A in M83. For the source closest to the SN position, the flux density was determined to be 0.30 +/- 0.05 mJy at 20 cm and 0.093 +/- 0.028 mJy at 6 cm. The flux density of the second nearby source was determined to be 0.29 +/- 0.05 at 20 cm and 0.13 +/- 0.028 at 6 cm. Both sources are non-thermal with spectral indices of alpha = -1.0 +/- 0.30 and -0.69 +/- 0.24, respectively. SN 1923A has been designated as a Type II-P. No Type II-P (other than SN 1987A) has been detected previously in the radio. The radio emission from both sources appears to be fading with time. At an age of approximately 68 years when we observed it, this would be the oldest radio supernova (of known age) yet detected

Transmission of High-Power Electron Beams Through Small Apertures

Tests were performed to pass a 100 MeV, 430 kWatt c.w. electron beam from the energy-recovery linac at the Jefferson Laboratory's FEL facility through a set of small apertures in a 127 mm long aluminum block. Beam transmission losses of 3 p.p.m. through a 2 mm diameter aperture were maintained during a 7 hour continuous run.Comment: arXiv admin note: text overlap with arXiv:1305.019

Effect of vaccination with a novel GnRH-based immunocontraceptive on immune responses and fertility in rats

1. As human-wildlife conflicts increase worldwide, novel methods are required for mitigating these conflicts. Fertility control, based on immunocontraceptives, has emerged as an alternative option to lethal methods for managing wildlife. 2. Immunocontraceptives are vaccines that generate an immune response to key components of an animal\u27s reproductive system. Some of these vaccines target the gonadotropin-releasing hormone (GnRH) and have been used successfully as contraceptives for many wildlife species. However, the need to capture animals for treatment limits the field applications of injectable vaccines. The availability of orally delivered immunocontraceptives would increase the breadth of applications of fertility control for wildlife management. 3. This study explored a new approach to developing an oral immunocontraceptive, exploiting the bioadhesive and immunologically active properties of killed Mycobacterium avium cell wall fragments (MAF). The MAF was conjugated to a GnRH recombinant protein called IMX294, used as a GnRH-specific immunogen. 4. An initial trial using the MAF-IMX294 conjugate provided the first evidence that an orally delivered immunocontraceptive vaccine could generate anti-GnRH antibody titres in laboratory rats. 5. Increasing the dose and frequency of vaccine administered to rats, in a second trial, enhanced the immune response, eliciting titres that reduced the proportion of females giving birth. This provided the first evidence of the contraceptive effect of an oral anti-GnRH vaccine. 6. Future work is required to further increase the immunogenic effect of the oral vaccine and to establish a dosing schedule that is effective for practical field applications

Measured Radiation and Background Levels During Transmission of Megawatt Electron Beams Through Millimeter Apertures

We report measurements of photon and neutron radiation levels observed while transmitting a 0.43 MW electron beam through millimeter-sized apertures and during beam-off, but accelerating gradient RF-on, operation. These measurements were conducted at the Free-Electron Laser (FEL) facility of the Jefferson National Accelerator Laboratory (JLab) using a 100 MeV electron beam from an energy-recovery linear accelerator. The beam was directed successively through 6 mm, 4 mm, and 2 mm diameter apertures of length 127 mm in aluminum at a maximum current of 4.3 mA (430 kW beam power). This study was conducted to characterize radiation levels for experiments that need to operate in this environment, such as the proposed DarkLight Experiment. We find that sustained transmission of a 430 kW continuous-wave (CW) beam through a 2 mm aperture is feasible with manageable beam-related backgrounds. We also find that during beam-off, RF-on operation, multipactoring inside the niobium cavities of the accelerator cryomodules is the primary source of ambient radiation when the machine is tuned for 130 MeV operation.Comment: 9 pages, 11 figures, submitted to Nuclear Instruments and Methods in Physics Research Section