Frequency and Severity of Neutropenia Associated with Food and Drug Administration Approved and Compounded Formulations of Lomustine in Dogs with Cancer.

BackgroundCompounded lomustine is used commonly in veterinary patients. However, the potential variability in these formulations is unknown and concern exists that compounded formulations of drugs may differ in potency from Food and Drug Administration (FDA)-approved products.Hypothesis/objectivesThe initial objective of this study was to evaluate the frequency and severity of neutropenia in dogs treated with compounded or FDA-approved formulations of lomustine. Subsequent analyses aimed to determine the potency of lomustine obtained from several compounding pharmacies.AnimalsThirty-seven dogs treated with FDA-approved or compounded lomustine.MethodsDogs that received compounded or FDA-approved lomustine and had pretreatment and nadir CBCs performed were eligible for inclusion. Variables assessed included lomustine dose, neutrophil counts, and severity of neutropenia. Lomustine 5 mg capsules from 5 compounding sources were tested for potency using high-pressure liquid chromatography (HPLC) with ultraviolet (UV) detection.ResultsTwenty-one dogs received FDA-approved lomustine and 16 dogs were treated with lomustine prescribed from a single compounding pharmacy. All dogs treated with FDA-approved lomustine were neutropenic after treatment; 15 dogs (71%) developed grade 3 or higher neutropenia. Four dogs (25%) given compounded lomustine became neutropenic, with 2 dogs (12.5%) developing grade 3 neutropenia. The potency of lomustine from 5 compounding pharmacies ranged from 50 to 115% of the labeled concentration, with 1 sample within ±10% of the labeled concentration.Conclusions and clinical importanceThese data support broader investigation into the potency and consistency of compounded chemotherapy drugs and highlight the potential need for greater oversight of these products

Analysis of Germanium Hydride Molecular Clusters

Isotope clusters in library electron ionization mass spectra of germanes often appear a few u lower than theoretically expected from elemental composition; for example, the dominant peak of the Ge4H10+ pattern is shifted 8 u down. This phenomenon is due to combinations of three essential components: the molecular ion GenH2n+2+ and two products of hydrogen elimination, GenH+ and Gen+. Using these components, isotope clusters can be accurately projected for germanium hydrides from Ge2H6 up to Ge5H12

Marginal Fluctuations of a Svalbard Surge-Type Tidewater Glacier, Blomstrandbreen, since the Little Ice Age: A Record of Three Surges

© 2016 Regents of the University of Colorado. Previous advances and retreats of Blomstrandbreen within the cold period known as the Little Ice Age, between approximately 1400 and 1920, are relatively well documented. The seafloor characteristics associated with these glacier fluctuations, and their importance for the identification of similar surge-type tidewater glaciers, are discussed. We use detailed multibeam-bathymetric data acquired within Nordvågen, the marine area offshore of Blomstrandbreen, to provide a new understanding of the style and pattern of deglaciation around Blomstrandhalvøya since Blomstrandbreen's neoglacial maximum. Glacial landforms on the seafloor of Nordvågen comprise overridden moraines, glacial lineations, terminal moraines, and annual recessional moraines. Crevasse-fill ridges, which are often regarded as a characteristic landform of surging tidewater glaciers, are present on only restricted areas of Nordvågen. Significantly, this study shows that large terminal surge moraines and numerous crevasse-fill ridges may not always be well developed in association with glacier surges, with implications for the identification of surges in the geological record. Using historical observations, aerial photographs, and satellite imagery of Blomstrandbreen, we have correlated former ice-marginal positions with mapped submarine landforms. Three surge events occurred during a pattern of overall retreat, with a spacing of about 50 years between active advance phases; this represents a relatively short quiescent phase for Svalbard glaciers. Average retreat rates of 10-50 m yr-1 are typical of the quiescent phase of the surge cycle, whereas surge advances vary from 200 m to over 725 m

Molecular Characterization and Expression of a Heat Shock Protein Gene (HSP90) from the Carmine Spider Mite, Tetranychus cinnabarinus (Boisduval)

In this study, the cDNA of Tetranychus cinnabarinus (Boisduval) (Acarina: Tetranychidae) HSP90 (designated TcHSP90) was cloned using a combination of the homology cloning and rapid amplification of cDNA ends (RACE) approaches. The full-length cDNA of TcHSP90 is 2595 bp, including a 5′-untranslated region (UTR) of 177 bp, 3′-UTR of 249 bp, and an open reading frame (ORF) of 2169 bp. The ORF encodes a polypeptide of 722 amino acids with a predicted molecular weight of 83.45 kDa and a theoretical isoelectric point of 4.81. There is an mRNA polyadenylation signal of ATTAAA at the positions 2558–2564. In addition, the expression pattern of TcHSP90 mRNA relative to that of β-actin gene in the three stains of T. cinnabarinus (AbR, abamectin-resistant strain; HR, heat-resistant strain; SS, the susceptible strain) were examined by using fluorescent real time quantitative PCR after the impact of abamectin, high and low temperature, respectively. The results showed that under the normal condition, the mRNA level of TcHSP90 was 1.64 and 1.29-fold higher in the AbR and HR than in SS, respectively. After 8 h treatment with abamectin, the TcHSP90 mRNA levels of SS, AbR, and HR were 1.25, 1.87, and 2.05-fold higher than those of their untreated controls, respectively. The TcHSP90 mRNA levels of SS, AbR, and HR were also significantly increased after being induced at 40° C for 1 h, and they were 3.76, 3.42, and 3.79-fold higher than those of their untreated controls, respectively. The mRNA level of TcHSP90 was also significantly increased after being induced at 4° C for 1 h. These results suggest that TcHSP90 might be involved in the abamectin and extreme temperature resistance or tolerance

Anthropogenic Impacts on Aquatic Insects in Six Streams of South Western Ghats

Diversity patterns of aquatic insects among sampling sites lying with!ç the unprotected and protected areas of Western Ghats were studied. This study primarily emphasizes whether anthropogenic influence is the prime cause for the presence of aquatic insects especialIy of pollution-sensitive organisms belonging to the orders Ephemeroptera, Plecoptera and Trichoptera, or to factors such as the physico-chemical features of the water, or sampling methods. Six streams were sampled quantitatively, of which three streams (Abbifalls, Monkey falls and SiIver Cascade) were within protected areas and the remaining three streams (Kumbakarai, Shenbagadevi and Manimutharu falls) were in unprotected areas. A total of 3,209 individual aquatic insects belonging to 25 genera, 18 families and 7 orders were collected. The highest species richness and abundance was observed in Monkey falls followed by Kumbakkarai falls. Large çumbers of more habitat-sensitive organisms such as Ecdyonurus sp., Epeorus sp., Thalerosphyrus sp., Euthraulus sp., and Nathanella sp., were found in Monkey falls. Though the species assemblage was somewhat different, pollution-sensitive taxa were also observed in Kumbakkarai falls. Shenbagadevi and Manimutharu falls had a lower diversity of aquatic insects. The likely causes of these differences are discussed

Cortical thickness, surface area and volume measures in Parkinson's disease, multiple system atrophy and progressive supranuclear palsy

OBJECTIVE Parkinson's disease (PD), Multiple System Atrophy (MSA) and Progressive Supranuclear Palsy (PSP) are neurodegenerative diseases that can be difficult to distinguish clinically. The objective of the current study was to use surface-based analysis techniques to assess cortical thickness, surface area and grey matter volume to identify unique morphological patterns of cortical atrophy in PD, MSA and PSP and to relate these patterns of change to disease duration and clinical features. METHODS High resolution 3D T1-weighted MRI volumes were acquired from 14 PD patients, 18 MSA, 14 PSP and 19 healthy control participants. Cortical thickness, surface area and volume analyses were carried out using the automated surface-based analysis package FreeSurfer (version 5.1.0). Measures of disease severity and duration were assessed for correlation with cortical morphometric changes in each clinical group. RESULTS Results show that in PSP, widespread cortical thinning and volume loss occurs within the frontal lobe, particularly the superior frontal gyrus. In addition, PSP patients also displayed increased surface area in the pericalcarine. In comparison, PD and MSA did not display significant changes in cortical morphology. CONCLUSION These results demonstrate that patients with clinically established PSP exhibit distinct patterns of cortical atrophy, particularly affecting the frontal lobe. These results could be used in the future to develop a useful clinical application of MRI to distinguish PSP patients from PD and MSA patients

Isotope Analysis Reveals Foraging Area Dichotomy for Atlantic Leatherback Turtles

Background: The leatherback turtle (Dermochelys coriacea) has undergone a dramatic decline over the last 25 years, and this is believed to be primarily the result of mortality associated with fisheries bycatch followed by egg and nesting female harvest. Atlantic leatherback turtles undertake long migrations across ocean basins from subtropical and tropical nesting beaches to productive frontal areas. Migration between two nesting seasons can last 2 or 3 years, a time period termed the remigration interval (RI). Recent satellite transmitter data revealed that Atlantic leatherbacks follow two major dispersion patterns after nesting season, through the North Gulf Stream area or more eastward across the North Equatorial Current. However, information on the whole RI is lacking, precluding the accurate identification of feeding areas where conservation measures may need to be applied. Methodology/Principal Findings: Using stable isotopes as dietary tracers we determined the characteristics of feeding grounds of leatherback females nesting in French Guiana. During migration, 3-year RI females differed from 2-year RI females in their isotope values, implying differences in their choice of feeding habitats (offshore vs. more coastal) and foraging latitude (North Atlantic vs. West African coasts, respectively). Egg-yolk and blood isotope values are correlated in nesting females, indicating that egg analysis is a useful tool for assessing isotope values in these turtles, including adults when not available. Conclusions/Significance: Our results complement previous data on turtle movements during the first year following the nesting season, integrating the diet consumed during the year before nesting. We suggest that the French Guiana leatherback population segregates into two distinct isotopic groupings, and highlight the urgent need to determine the feeding habitats of the turtle in the Atlantic in order to protect this species from incidental take by commercial fisheries. Our results also emphasize the use of eggs, a less-invasive sampling material than blood, to assess isotopic data and feeding habits for adult female leatherbacks

A comparison of customised and prefabricated insoles to reduce risk factors for neuropathic diabetic foot ulceration: a participant-blinded randomised controlled trial.

UNLABELLED: BACKGROUND: Neuropathic diabetic foot ulceration may be prevented if the mechanical stress transmitted to the plantar tissues is reduced. Insole therapy is one practical method commonly used to reduce plantar loads and ulceration risk. The type of insole best suited to achieve this is unknown. This trial compared custom-made functional insoles with prefabricated insoles to reduce risk factors for ulceration of neuropathic diabetic feet. METHOD: A participant-blinded randomised controlled trial recruited 119 neuropathic participants with diabetes who were randomly allocated to custom-made functional or prefabricated insoles. Data were collected at issue and six month follow-up using the F-scan in-shoe pressure measurement system. Primary outcomes were: peak pressure, forefoot pressure time integral, total contact area, forefoot rate of load, duration of load as a percentage of stance. Secondary outcomes were patient perceived foot health (Bristol Foot Score), quality of life (Audit of Diabetes Dependent Quality of Life). We also assessed cost of supply and fitting. Analysis was by intention-to-treat. RESULTS: There were no differences between insoles in peak pressure, or three of the other four kinetic measures. The custom-made functional insole was slightly more effective than the prefabricated insole in reducing forefoot pressure time integral at issue (27% vs. 22%), remained more effective at six month follow-up (30% vs. 24%, p=0.001), but was more expensive (UK £656 vs. £554, p<0.001). Full compliance (minimum wear 7 hours a day 7 days per week) was reported by 40% of participants and 76% of participants reported a minimum wear of 5 hours a day 5 days per week. There was no difference in patient perception between insoles. CONCLUSION: The custom-made insoles are more expensive than prefabricated insoles evaluated in this trial and no better in reducing peak pressure. We recommend that where clinically appropriate, the more cost effective prefabricated insole should be considered for use by patients with diabetes and neuropathy. TRIAL REGISTRATION: Clinical trials.gov (NCT00999635). Note: this trial was registered on completion

Estimation of the national disease burden of influenza-associated severe acute respiratory illness in Kenya and Guatemala : a novel methodology

Background: Knowing the national disease burden of severe influenza in low-income countries can inform policy decisions around influenza treatment and prevention. We present a novel methodology using locally generated data for estimating this burden. Methods and Findings: This method begins with calculating the hospitalized severe acute respiratory illness (SARI) incidence for children <5 years old and persons ≥5 years old from population-based surveillance in one province. This base rate of SARI is then adjusted for each province based on the prevalence of risk factors and healthcare-seeking behavior. The percentage of SARI with influenza virus detected is determined from provincial-level sentinel surveillance and applied to the adjusted provincial rates of hospitalized SARI. Healthcare-seeking data from healthcare utilization surveys is used to estimate non-hospitalized influenza-associated SARI. Rates of hospitalized and non-hospitalized influenza-associated SARI are applied to census data to calculate the national number of cases. The method was field-tested in Kenya, and validated in Guatemala, using data from August 2009–July 2011. In Kenya (2009 population 38.6 million persons), the annual number of hospitalized influenza-associated SARI cases ranged from 17,129–27,659 for children <5 years old (2.9–4.7 per 1,000 persons) and 6,882–7,836 for persons ≥5 years old (0.21–0.24 per 1,000 persons), depending on year and base rate used. In Guatemala (2011 population 14.7 million persons), the annual number of hospitalized cases of influenza-associated pneumonia ranged from 1,065–2,259 (0.5–1.0 per 1,000 persons) among children <5 years old and 779–2,252 cases (0.1–0.2 per 1,000 persons) for persons ≥5 years old, depending on year and base rate used. In both countries, the number of non-hospitalized influenza-associated cases was several-fold higher than the hospitalized cases. Conclusions: Influenza virus was associated with a substantial amount of severe disease in Kenya and Guatemala. This method can be performed in most low and lower-middle income countries

Testing the cognitive-behavioural maintenance models across DSM-5 bulimic-type eating disorder diagnostic groups: A multi-centre study

The original cognitive-behavioural (CB) model of bulimia nervosa, which provided the basis for the widely used CB therapy, proposed that specific dysfunctional cognitions and behaviours maintain the disorder. However, amongst treatment completers, only 40–50 % have a full and lasting response. The enhanced CB model (CB-E), upon which the enhanced version of the CB treatment was based, extended the original approach by including four additional maintenance factors. This study evaluated and compared both CB models in a large clinical treatment seeking sample (N = 679), applying both DSM-IV and DSM-5 criteria for bulimic-type eating disorders. Application of the DSM-5 criteria reduced the number of cases of DSM-IV bulimic-type eating disorders not otherwise specified to 29.6 %. Structural equation modelling analysis indicated that (a) although both models provided a good fit to the data, the CB-E model accounted for a greater proportion of variance in eating-disordered behaviours than the original one, (b) interpersonal problems, clinical perfectionism and low self-esteem were indirectly associated with dietary restraint through over-evaluation of shape and weight, (c) interpersonal problems and mood intolerance were directly linked to binge eating, whereas restraint only indirectly affected binge eating through mood intolerance, suggesting that factors other than restraint may play a more critical role in the maintenance of binge eating. In terms of strength of the associations, differences across DSM-5 bulimic-type eating disorder diagnostic groups were not observed. The results are discussed with reference to theory and research, including neurobiological findings and recent hypotheses