MicroPulse™ transscleral cyclophotocoagulation in the equine patient: A case series of four horses.

OBJECTIVE: To describe the clinical application and outcome of MicroPulse™ transscleral cyclophotocoagulation (MP-TSCPC) treatment in horses with glaucoma. ANIMALS STUDIED: Four client-owned horses with primary (n = 2) or secondary (n = 2) glaucoma. METHODS: Horses were treated with MP-TSCPC under standing sedation with a minimum of 30 days of follow-up (range 30-1241 days). Affected eyes were treated with a 31.3% duty cycle and 3000 mW laser power for a total of 180 s. Data collected included signalment, pre- and post-procedure intraocular pressures (IOPs), laser settings, medications, complications, and repeat therapy. RESULTS: Four horses (5 eyes) received at least one treatment with MP-TSCPC. Mean preoperative IOP was 44 mmHg (range 33-49 mmHg). The immediate mean postoperative IOP was 34 mmHg (4 eyes; range 19-55 mmHg). At 1 week, IOP was 38 mmHg (5 eyes; range 21-80 mmHg), at 2 weeks was 40 mmHg (3 eyes, range 17-80 mmHg), at 1 month was 35 mmHg (5 eyes; range 20-50 mmHg), at 3 months was 18 mmHg (2 eyes; range 14-21 mmHg), at 6 months was 35 mmHg (2 eyes; range 30-39 mmHg), and at >300 days was 24 mmHg (3 eyes; range 18-29 mmHg). Complications included corneal ulceration (n = 1 eye), uncontrolled IOP (n = 3 eyes), and need for repeat treatment (n = 2 eyes). CONCLUSIONS: MP-TSCPC used with the above-described settings was unsuccessful in treating the majority of cases. Future studies should be targeted at primary glaucoma cases and with use of alternative laser settings.

Community resilience in a rural food system: documenting pathways to nutrition solutions.

OBJECTIVE: To describe and determine the barriers and facilitators to food-related health behaviors of residents in a rural Mississippi Delta community. STUDY DESIGN: Descriptive study of qualitative interviews. METHODS: A non-random sample of 34 low-income, food-insecure adults residing in a rural Mississippi Delta community were interviewed using fuzzy cognitive mapping, a mixed methods approach. RESULTS: Participants strongly emphasized the time restraints they faced in both procuring and preparing foods, due to substantial travel time required to procure groceries. Participants also identified key facilitators to healthy eating behaviors, including seasonal produce stands, foraging, fishing, home provisioning, and access to the local food pantry. These barriers and facilitators are highly interconnected with other influential factors including poverty, lack of health care, unemployment, and faith-based support systems. CONCLUSIONS: While the connection between low food access and poor eating habits is well researched, this novel mixed-method approach details two important elements missing from the literature: (1) other factors often overlooked that mitigate or exacerbate this relationship and (2) the dynamic nature of the relationships between these factors, poor eating habits, and health. Additionally, this research examines these relationships in an underrepresented rural minority population where resources needed to mitigate poor health are often much more limited. Findings from this study are critical to health and food policy in Mississippi and more generally, rural communities.

Relationship between Coating-Induced Soot Aggregate Restructuring and Primary Particle Number.

The restructuring of monodisperse soot aggregates due to coatings of secondary organic aerosol (SOA) was investigated in a series of photo-oxidation chamber experiments. Soot aggregates were generated by one of three sources (an ethylene premixed burner, a methane inverted diffusion burner, or a diesel generator), treated by denuding, size-selected by a differential mobility analyzer, and injected into a smog chamber, where they were exposed to the photo-oxidation products of p-xylene, which partitioned to form SOA coatings. The evolution of aggregates from their initial to final morphologies was investigated in situ by mobility and mass measurements and ex situ by transmission electron microscopy. At a given initial aggregate mobility diameter, diesel aggregates are less dense and composed of smaller primary particles than those generated by the two burners, and they restructure to a smaller final mobility diameter. Remarkably, the final degrees of restructuring of aggregates from all three sources exhibit the same linear dependence on the number of primary particles per aggregate. The observed linear relationship, valid for the atmospherically relevant SOA coating investigated here, could allow modelers to predict the evolution of aggregate morphology based on a single property of the aggregates.

Rigorous control conditions diminish treatment effects in weight loss-randomized controlled trials.

BACKGROUND: It has not been established whether control conditions with large weight losses (WLs) diminish expected treatment effects in WL or prevention of weight gain (PWG)-randomized controlled trials (RCTs). SUBJECTS/METHODS: We performed a meta-analysis of 239 WL/PWG RCTs that include a control group and at least one treatment group. A maximum likelihood meta-analysis framework was used to model and understand the relationship between treatment effects and control group outcomes. RESULTS: Under the informed model, an increase in control group WL of 1 kg corresponds with an expected shrinkage of the treatment effect by 0.309 kg (95% confidence interval (-0.480, -0.138), P=0.00081); this result is robust against violations of the model assumptions. CONCLUSIONS: We find that control conditions with large WLs diminish expected treatment effects. Our investigation may be helpful to clinicians as they design future WL/PWG studies.

Predicting adult weight change in the real world: a systematic review and meta-analysis accounting for compensatory changes in energy intake or expenditure.

BACKGROUND: Public health and clinical interventions for obesity in free-living adults may be diminished by individual compensation for the intervention. Approaches to predict weight outcomes do not account for all mechanisms of compensation, so they are not well suited to predict outcomes in free-living adults. Our objective was to quantify the range of compensation in energy intake or expenditure observed in human randomized controlled trials (RCTs). METHODS: We searched multiple databases (PubMed, CINAHL, SCOPUS, Cochrane, ProQuest, PsycInfo) up to 1 August 2012 for RCTs evaluating the effect of dietary and/or physical activity interventions on body weight/composition. INCLUSION CRITERIA: subjects per treatment arm ≥5; ≥1 week intervention; a reported outcome of body weight/body composition; the intervention was either a prescribed amount of over- or underfeeding and/or supervised or monitored physical activity was prescribed; ≥80% compliance; and an objective method was used to verify compliance with the intervention (for example, observation and electronic monitoring). Data were independently extracted and analyzed by multiple reviewers with consensus reached by discussion. We compared observed weight change with predicted weight change using two models that predict weight change accounting only for metabolic compensation. FINDINGS: Twenty-eight studies met inclusion criteria. Overfeeding studies indicate 96% less weight gain than expected if no compensation occurred. Dietary restriction and exercise studies may result in up to 12-44% and 55-64% less weight loss than expected, respectively, under an assumption of no behavioral compensation. INTERPRETATION: Compensation is substantial even in high-compliance conditions, resulting in far less weight change than would be expected. The simple algorithm we report allows for more realistic predictions of intervention effects in free-living populations by accounting for the significant compensation that occurs.

Phylogenetic and structural response of heterotrophic bacteria to dissolved organic matter of different chemical composition in a continuous culture study.

Dissolved organic matter (DOM) and heterotrophic bacteria are highly diverse components of the ocean system, and their interactions are key in regulating the biogeochemical cycles of major elements. How chemical and phylogenetic diversity are linked remains largely unexplored to date. To investigate interactions between bacterial diversity and DOM, we followed the response of natural bacterial communities to two sources of phytoplankton-derived DOM over six bacterial generation times in continuous cultures. Analyses of total hydrolysable neutral sugars and amino acids, and ultrahigh resolution mass spectrometry revealed large differences in the chemical composition of the two DOM sources. According to 454 pyrosequences of 16S ribosomal ribonucleic acid genes, diatom-derived DOM sustained higher levels of bacterial richness, evenness and phylogenetic diversity than cyanobacteria-derived DOM. These distinct community structures were, however, not associated with specific taxa. Grazing pressure affected bacterial community composition without changing the overall pattern of bacterial diversity levels set by DOM. Our results demonstrate that resource composition can shape several facets of bacterial diversity without influencing the phylogenetic composition of bacterial communities, suggesting functional redundancy at different taxonomic levels for the degradation of phytoplankton-derived DOM.

Psychological influences predict recovery following exercise induced shoulder pain.

Predicting recovery following muscle injury can be difficult because it involves consideration of multiple factors. Our objective was to determine if psychological factors, sex, and peak pain and disability ratings could be predictive of delayed recovery following induced muscle injury. Healthy untrained volunteers (n=126; M:F 51:75) underwent a concentric/eccentric isokinetic exercise protocol on their dominant shoulder to induce fatigue, with individuals who reported pain (>0/10) at 96 h being classified as "not recovered". Individuals experiencing pain at 48 h were more likely not to be recovered (O.R.=1.62, p<0.001). Additionally, individuals with higher scores in pain catastrophizing at 48 h were more likely to experience pain at 96 h (O.R.=1.06, p<0.001). Pain duration (in days) was associated with pain scores at 48 h (ß=0.385, p<0.001) and baseline anxiety (ß=0.220, p=0.007). Fear of movement/re-injury at 96 h was found to be associated with pain catastrophizing at 48 h (ß=0.537, p<0.001) and baseline levels of fear of pain (ß=0.217, p=0.004). This study provides preliminary evidence that higher pain levels and pain catastrophizing following acute muscle injury are associated with poor recovery, higher fear of movement/re-injury and longer pain duration.

Can a weight loss of one pound a week be achieved with a 3500-kcal deficit? Commentary on a commonly accepted rule.

Despite theoretical evidence that the model commonly referred to as the 3500-kcal rule grossly overestimates actual weight loss, widespread application of the 3500-kcal formula continues to appear in textbooks, on respected government- and health-related websites, and scientific research publications. Here we demonstrate the risk of applying the 3500-kcal rule even as a convenient estimate by comparing predicted against actual weight loss in seven weight loss experiments conducted in confinement under total supervision or objectively measured energy intake. We offer three newly developed, downloadable applications housed in Microsoft Excel and Java, which simulates a rigorously validated, dynamic model of weight change. The first two tools available at http://www.pbrc.edu/sswcp, provide a convenient alternative method for providing patients with projected weight loss/gain estimates in response to changes in dietary intake. The second tool, which can be downloaded from the URL http://www.pbrc.edu/mswcp, projects estimated weight loss simultaneously for multiple subjects. This tool was developed to inform weight change experimental design and analysis. While complex dynamic models may not be directly tractable, the newly developed tools offer the opportunity to deliver dynamic model predictions as a convenient and significantly more accurate alternative to the 3500-kcal rule.

Getting carried away: a note showing baseline observation carried forward (BOCF) results can be calculated from published complete-cases results.

OBJECTIVE: Randomized controlled trials (RCTs) in obesity are plagued by missing data due to participant dropouts. Most methodologists and regulatory bodies agree that the primary analysis of such RCTs should be based on the intent-to-treat (ITT) principle, such that all randomized subjects are included in the analysis, even those who dropped out. Unfortunately, some authors do not include an ITT analysis in their published reports. Here we show that one form of ITT analysis, baseline observation carried forward (BOCF), can be performed utilizing only information available in a published complete-case (CC) analysis, permitting readers, editors, meta-analysts and regulators to easily conduct their own ITT analyses when the original authors do not report one. METHOD: We mathematically derive a simple method for estimating and testing treatment effects using the BOCF to allow a more conservative comparison of treatment effects when there are dropouts in a clinical trial. We provide two examples of this method using available CC analysis data from reported obesity trials to illustrate the application for readers who wish to determine a range of treatment effects based on published summary statistics. CONCLUSION: Commonly used CC analyses may lead to inflated type I error rates and/or treatment effect estimates. The method described herein can be useful for researchers who wish to estimate a conservative range of plausible treatment effects based on limited reported data. Limitations of this method are discussed.

Is funding source related to study reporting quality in obesity or nutrition randomized control trials in top-tier medical journals?

BACKGROUND: Faithful and complete reporting of trial results is essential to the validity of the scientific literature. An earlier systematic study of randomized controlled trials (RCTs) found that industry-funded RCTs appeared to be reported with greater quality than non-industry-funded RCTs. The aim of this study was to examine the association between systematic differences in reporting quality and funding status (that is, industry funding vs non-industry funding) among recent obesity and nutrition RCTs published in top-tier medical journals. METHODS: Thirty-eight obesity or nutrition intervention RCT articles were selected from high-profile, general medical journals (The Lancet, Annals of Internal Medicine, JAMA and the British Medical Journal) published between 2000 and 2007. Paired papers were selected from the same journal published in the same year, one with and the other without industry funding. The following identifying information was redacted: journal, title, authors, funding source and institution(s). Then three raters independently and blindly rated each paper according to the Chalmers method, and total reporting quality scores were calculated. FINDINGS: The inter-rater reliability (Cronbach's alpha) was 0.82 (95% confidence interval = 0.80-0.84). The total mean (M) and s.d. of Chalmers Index quality score (out of a possible 100) for industry-funded studies were M = 84.5, s.d. = 7.04 and for non-industry-funded studies they were M = 79.4, s.d. = 13.00. A Wilcoxon matched-pairs signed-ranks test indicates no significant rank difference in the distributions of total quality scores between funding sources, Z = -0.966, P = 0.334 (two tailed). INTERPRETATION: Recently published RCTs on nutrition and obesity that appear in top-tier journals seem to be equivalent in quality of reporting, regardless of funding source. This may be a result of recent reporting of quality statements and efforts of journal editors to raise all papers to a common standard.

Modified release terbutaline (SKP1052) for hypoglycaemia prevention: a proof-of-concept study in people with type 1 diabetes mellitus.

AIMS: In this randomized, single blind, cross-over study 2.5 mg and 5 mg of the modified-release terbutaline formulation (SKP-1052) were compared with conventional immediate-release terbutaline (IRT, 5 mg) and placebo on overnight blood glucose (BG) and hypoglycaemia in 30 subjects with type 1 diabetes mellitus. METHODS: Subjects received subcutaneous injections of insulin glargine (individualized doses) before dinner. SKP-1052, IRT or placebo was administered around 21:00 hours. BG and terbutaline concentrations were monitored overnight for 10 h post-dosing. Endpoints comprised of the nadir BG (BGn 0-10 h, primary endpoint), mean overnight BG (BGmean), morning BG (BGmorning) and hypoglycaemia rates as well as pharmacokinetic (PK) endpoints. RESULTS: SKP-1052 delayed release of terbutaline by 2 h [PK-tmax (mean ± SD) 5.0 ± 2.1 h (2.5 mg) and 4.7 ± 1.7 h (5 mg) vs. 2.6 ± 1.3 h with IRT, p < 0.01, respectively]. Compared with placebo, no significant differences were observed for BGn 0-10 h across treatments, but both 5 mg formulations showed less hypoglycaemic events [10 (IRT), 16 (SKP-1052) vs. 33], higher BGmean (120, 114 and 95 mg/dl) and BGmorning (126, 126 and 101 mg/dl, all comparisons p < 0.05 vs. placebo). Numerically higher BG-levels between 3 and 8 h post-dosing were observed with 2.5 mg SKP-1052 vs. placebo. CONCLUSIONS: Compared with IRT SKP-1052 delays release of terbutaline. 2.5 mg SKP-1052 led to numerically higher BG 3 to 8 h post-dose without fasting hyperglycaemia while 5 mg SKP-1052 resulted in fasting hyperglycaemia vs. placebo. Future studies will investigate optimized doses of SKP-1052 for nocturnal hypoglycaemia prevention.

Implementation of a Talbot-Lau x-ray deflectometer diagnostic platform for the OMEGA EP laser.

A Talbot-Lau X-ray Deflectometer (TXD) was implemented in the OMEGA EP laser facility to characterize the evolution of an irradiated foil ablation front by mapping electron densities >1022 cm-3 by means of Moiré deflectometry. The experiment used a short-pulse laser (30-100 J, 10 ps) and a foil copper target as an x-ray backlighter source. In the first experimental tests performed to benchmark the diagnostic platform, grating survival was demonstrated and x-ray backlighter laser parameters that deliver Moiré images were described. The necessary modifications to accurately probe the ablation front through TXD using the EP-TXD diagnostic platform are discussed.

KLP38B: a mitotic kinesin-related protein that binds PP1.

We have identified a new member of the kinesin superfamily in Drosophila, KLP38B (kinesin-like protein at 38B). KLP38B was isolated through its two-hybrid interaction with the catalytic subunit of type 1 serine/threonine phosphoprotein phosphatase (PP1). We demonstrate that recombinant KLP38B and PP1 associate in vitro. This is the first demonstration of direct binding of a kinesin-related protein to a regulatory enzyme. Though most closely related to the Unc-104 subfamily of kinesin-related proteins, KLP38B is expressed only in proliferating cells. KLP38B mutants show cell proliferation defects in many tissues. KLP38B is required for normal chromatin condensation as embryos from KLP38B mutant mothers have undercondensed chromatin at metaphase and anaphase. This is the first time that a kinesin-related protein has been shown to have such a role. Incomplete lethality of a strong KLP38B allele suggests partial redundancy with one or more additional kinesin-related proteins.

Mirex: an unrecognized contaminant of fishes from Lake Ontario.

A perchlorinated, cage-structured hydrocarbon, C(10)C(l2), also known as mirex or Dechlorane, has been identified in fish samples from the Bay of Quinte, Lake Ontario, Canada. The compound coelutes with polychlorinated biphenyls (PCB's) in residue cleanup procedures and under standard gas chromatographic conditions. Mirex has never been registered for use as an insecticide in Canada, nor does it appear to be in use in any area of the United States discharging water into Lake Ontario or its tributaries. It seems likely, therefore, that this compound is another widespread environmental contaminant of extremely high geochemical stability and as yet only superficially investigated biological activities. Under standard gas chromatographic conditions its peak is superimposed on that of the PCB's, and, as a result, the presence of mirex may have been unrecognized and it may therefore have been misinterpreted as a PCB isomer.

Polyelectrolytes: potential chloroform precursors.

Chloroform residues in potable water are generally thought to be derived only from the organic matter in the raw water upon chlorination. However, formation of chloroform at concentrations of a few micrograms per liter from widely used polyelectrolyte coagulants and coagulant aids has now been observed. Most of the ten commercial polyelectrolyte formulations tested reacted with chlorine to form chloroform under thermal conditions. This reaction was found to be strongly activated by ultraviolet irradiation. Since the chemical composition of polyelectrolytes and their impurities are little known, further studies are required before a full assessment of their benefits and potential harm can be made.

Production of refractory dissolved organic matter by bacteria.

Most of the oceanic reservoir of dissolved organic matter (DOM) is of marine origin and is resistant to microbial oxidation, but little is known about the mechanisms of its formation. In a laboratory study, natural assemblages of marine bacteria rapidly (in <48 hours) utilized labile compounds (glucose, glutamate) and produced refractory DOM that persisted for more than a year. Only 10 to 15% of the bacterially derived DOM was identified as hydrolyzable amino acids and sugars, a feature consistent with marine DOM. These results suggest that microbial processes alter the molecular structure of DOM, making it resistant to further degradation and thereby preserving fixed carbon in the ocean.

Associative learning disrupted by impaired Gs signaling in Drosophila mushroom bodies.

Disruptions in mushroom body (MB) or central complex (CC) brain structures impair Drosophila associative olfactory learning. Perturbations in adenosine 3',5' monophosphate signaling also disrupt learning. To integrate these observations, expression of a constitutively activated stimulatory heterotrimeric guanosine triphosphate-binding protein alpha subunit (Galphas*) was targeted to these brain structures. The ability to associate odors with electroshock was abolished when Galphas* was targeted to MB, but not CC, structures, whereas sensorimotor responses to these stimuli remained normal. Expression of Galphas* did not affect gross MB morphology, and wild-type Galphas expression did not affect learning. Thus, olfactory learning depends on regulated Gs signaling in Drosophila MBs.

Conditional restoration of hippocampal synaptic potentiation in Glur-A-deficient mice.

Plasticity of mature hippocampal CA1 synapses is dependent on l-alpha-amino-3-hydroxy-5-methylisoxazole-4-propionate (AMPA) receptors containing the glutamate receptor A (GluR-A) subunit. In GluR-A-deficient mice, plasticity could be restored by controlled expression of green fluorescent protein (GFP)-tagged GluR-A, which contributes to channel formation and displayed the developmental redistribution of AMPA receptors in CA1 pyramidal neurons. Long-term potentiation (LTP) induced by pairing or tetanic stimulation was rescued in adult GluR-A(-/-) mice when (GFP)GluR-A expression was constitutive or induced in already fully developed pyramidal cells. This shows that GluR-A-independent forms of synaptic plasticity can mediate the establishment of mature hippocampal circuits that are prebuilt to express GluR-A-dependent LTP.

Importance of AMPA receptors for hippocampal synaptic plasticity but not for spatial learning.

Gene-targeted mice lacking the L-alpha-amino-3-hydroxy-5-methylisoxazole-4-propionate (AMPA) receptor subunit GluR-A exhibited normal development, life expectancy, and fine structure of neuronal dendrites and synapses. In hippocampal CA1 pyramidal neurons, GluR-A-/- mice showed a reduction in functional AMPA receptors, with the remaining receptors preferentially targeted to synapses. Thus, the CA1 soma-patch currents were strongly reduced, but glutamatergic synaptic currents were unaltered; and evoked dendritic and spinous Ca2+ transients, Ca2+-dependent gene activation, and hippocampal field potentials were as in the wild type. In adult GluR-A-/- mice, associative long-term potentiation (LTP) was absent in CA3 to CA1 synapses, but spatial learning in the water maze was not impaired. The results suggest that CA1 hippocampal LTP is controlled by the number or subunit composition of AMPA receptors and show a dichotomy between LTP in CA1 and acquisition of spatial memory.