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A perceived dissonance exists between the stated conservation mission of modern zoos and the composition of species in their care. A bias toward charismatic taxa over threatened ones has been demonstrated in several studies. However, these prior examinations have principally relied on species threat status derived from global lists, and threat status reported for species on national and subnational lists often differ from global assessments. It has been suggested that some globally non‐threatened species maintained in zoos might fulfill local conservation priorities. In this study, we compare local threat status and zoo population size for native bird, mammal, reptile and amphibian species in North American zoos to assess the representation of locally threatened taxa. We found that native locally threatened species were kept in North American zoos slightly less than would be expected by chance; however, of the species that were represented in zoos, those that were threatened in more of the subnational regions where they occurred averaged larger populations within zoos. This suggests that the direct contribution from zoo animals to the conservation of locally threatened species is relatively limited with respect to taxonomic coverage, but this contribution may be underestimated by strictly counting the threatened species kept in zoos. [ABSTRACT FROM AUTHOR]

Background Australian veterans have an increased risk of posttraumatic stress disorder (PTSD) Guilt is a common post-trauma reaction; however, research in this area is limited Purpose This study aimed to explore the relationship between guilt, PTSD severity, alcohol use, anger, history of suicide attempts and deployment period among Australian veterans with PTSD Material and Methods A retrospective analysis was conducted on 219 ex-service personnel diagnosed with PTSD who attended a Military Trauma Recovery Day Program Veterans completed self-report questionnaires as well as a clinician-administered PTSD assessment tool Demographic information and self-reported history of suicide attempts were also recorded Results Guilt scores were significantly correlated with PTSD severity (R=0 411), anger (R=0 373) and alcohol use (R=0 239) Guilt was most strongly correlated with the re-experiencing cluster of PTSD (R=0 420), although it was significantly correlated with all clusters (hyperarousal R=0 343, and avoidance R=0 327) Guilt scores were significantly higher in those who had attempted suicide and for contemporary veterans Conclusions In Australian veterans with PTSD, guilt was significantly associated with PTSD severity, anger, alcohol use, attempted suicide and being a contemporary veteran The study highlights the importance of guilt identification and treatment by clinicians for improved outcomes [ABSTRACT FROM AUTHOR]

Background: Individualizing goals for people with type 2 diabetes may result in deintensification of medication, but a comprehensive picture of deprescribing practices is lacking. Aims: To conduct a scoping review in order to assess the rates, determinants and success of implementing deprescribing of glucose‐, blood pressure‐ or lipid‐lowering medications in people with diabetes. Methods: A systematic search on MEDLINE and Embase between January 2007 and January 2019 was carried out for deprescribing studies among people with diabetes. Outcomes were rates of deprescribing related to participant characteristics, the determinants and success of deprescribing, and its implementation. Critical appraisal was conducted using predefined tools. Results: Fourteen studies were included; eight reported on rates, nine on determinants and six on success and implementation. Bias was high for studies on success of deprescribing. Deprescribing rates ranged from 14% to 27% in older people with low HbA1c levels, and from 16% to 19% in older people with low systolic blood pressure. Rates were not much affected by age, gender, frailty or life expectancy. Rates were higher when a reminder system was used to identify people with hypoglycaemia, which led to less overtreatment and fewer hypoglycaemic events. Most healthcare professionals accepted the concept of deprescribing but differed on when to conduct it. Deprescribing glucose‐lowering medications could be successfully conducted in 62% to 75% of participants with small rises in HbA1c. Conclusions: Deprescribing of glucose‐lowering medications seems feasible and acceptable, but was not widely implemented in the covered period. Support systems may enhance deprescribing. More studies on deprescribing blood pressure‐ and lipid‐lowering medications in people with diabetes are needed. [ABSTRACT FROM AUTHOR]

Background: Reported prevalence of driver gene mutations in non-small-cell lung cancer (NSCLC) is highly variable and clinical correlations are emerging. Using NSCLC biomaterial and clinical data from the European Thoracic Oncology Platform Lungscape iBiobank, we explore the epidemiology of mutations and association to clinicopathologic features and patient outcome (relapse-free survival, time-to-relapse, overall survival). Methods: Clinically annotated, resected stage I-III NSCLC FFPE tissue was assessed for gene mutation using a microfluidicsbased multiplex PCR platform. Mutant-allele detection sensitivity is>1% for most of the ~150 (13 genes) mutations covered in the multiplex test. Results: Multiplex testing has been carried out in 2063 (76.2%) of the 2709 Lungscape cases (median follow-up 4.8 years). FFPE samples mostly date from 2005 to 2008, yet recently extracted DNA quality and quantity was generally good. Average DNA yield/case was 2.63 μg; 38 cases (1.4%) failed QC and were excluded from study; 95.1% of included cases allowed the complete panel of mutations to be tested. Most common were KRAS, MET, EGFR and PIK3CA mutations with overall prevalence of 23.0%, 6.8%, 5.4% and 4.9%, respectively. KRAS and EGFR mutations were significantly more frequent in adenocarcinomas: PIK3CA in squamous cell carcinomas. MET mutation prevalence did not differ between histology groups. EGFR mutations were found predominantly in never smokers; KRAS in current/former smokers. For all the above mutations, there was no difference in outcome between mutated and non-mutated cases. Conclusion: Archival FFPE NSCLC material is adequate for multiplex mutation analysis. In this large, predominantly European, clinically annotated stage I-III NSCLC cohort, none of the mutations characterized showed prognostic significance. [ABSTRACT FROM AUTHOR]

The evolution of personalised medicine in lung cancer has dramatically impacted diagnostic pathology. Current challenges centre on the growing demands placed on small tissue samples by molecular diagnostic techniques. In this review, expert recommendations are provided regarding successful identification of anaplastic lymphoma kinase (ALK)- rearranged non-small-cell lung cancer (NSCLC). Steps to correctly process and conserve tumour tissue during diagnostic testing are essential to ensure tissue availability. For example, storing extra tissue sections ready for molecular diagnostic steps allows faster testing and preserves tissue. Fluorescence in situ hybridisation (FISH) is commonly used to detect ALK rearrangements, with most laboratories favouring screening by immunohistochemistry followed by a confirmatory FISH assay. Reverse transcription-polymerase chain reaction can also identify ALK fusion gene mRNA transcripts but can be limited by the quality of RNA and the risk that rare fusion variants may not be captured. Next-generation sequencing (NGS) technology has recently provided an alternative method for detecting ALK rearrangements. While current experience is limited, NGS is set to become the most efficient approach as an increasing number of genetic abnormalities is required to be tested. Upfront, reflex testing for ALK gene rearrangement should become routine as ALK tyrosine kinase inhibitor therapy moves into the first-line setting. Guidelines recommend that EGFR and ALK tests are carried out in parallel on all confirmed and potential adenocarcinomas, and this is more efficient in terms of tissue usage and testing turnaround time for both of these actionable gene alterations. The practice of sequential testing is not recommended. Identification of ALK rearrangements is now essential for the diagnosis of NSCLC, underpinned by the benefits of ALK inhibitors. As scientific understanding and diagnostic technology develops, ALK testing will continue to be an evolving and challenging paradigm. [ABSTRACT FROM AUTHOR]

Dietary fermentable fiber is known to benefit intestinal health of companion animals. Soluble corn fiber (SCF) was evaluated for its chemical composition, nitrogen-corrected true ME (TMEn) content, in vitro digestion and fermentation characteristics, and in vivo effects on nutrient digestibility, fecal fermentation end products, and modulation of the fecal microbiome of dogs. Soluble corn fiber contained 78% total dietary fiber, all present as soluble dietary fiber; 56% was low molecular weight soluble fiber (did not precipitate in 95% ethanol). The SCF also contained 26% starch and 8% resistant starch and had a TMEn value of 2.6 kcal/g. Soluble corn fiber was first subjected to in vitro hydrolytic-enzymatic digestion to determine extent of digestibility and then fermented using dog fecal inoculum, with fermentative outcomes measured at 0, 3, 6, 9, and 12 h. Hydrolytic-enzymatic digestion of SCF was only 7%. In vitro fermentation showed increased (P < 0.05) concentrations of shortchain fatty acids through 12 h, with acetate, propionate, and butyrate reaching peak concentrations of 1,803, 926, and 112 μmol/g DM, respectively. Fermentability of SCF was higher (P < 0.05) than for cellulose but lower (P < 0.05) than for pectin. In the in vivo experiment, 10 female dogs (6.4 ± 0.2 yr and 22 ± 2.1 kg) received 5 diets with graded concentrations of SCF (0, 0.5, 0.75, 1.0, or 1.25% [as-is basis]) replacing cellulose in a replicated 5 × 5 Latin square design. Dogs were first acclimated to the experimental diets for 10 d followed by 4 d of total fecal collection. Fresh fecal samples were collected to measure fecal pH and fermentation end products and permit a microbiome analysis. For microbiome analysis, extraction of DNA was followed by amplification of the V4 to V6 variable region of the 16S rRNA gene using barcoded primers. Sequences were classified into taxonomic levels using a nucleotide basic local alignment search tool (BLASTn) against a curated GreenGenes database. Few changes in nutrient digestibility or fecal fermentation end products or stool consistency were observed, and no appreciable modulation of the fecal microbiome occurred. In conclusion, SCF was fermentable in vitro, but higher dietary concentrations may be necessary to elicit potential in vivo responses. [ABSTRACT FROM AUTHOR]

Background: Clozapine is effective for resistant schizophrenia. After two sudden deaths in physically well young men soon after starting clozapine, we investigated the cardiovascular complications for this drug.Methods: From January, 1993, to March, 1999, 8000 patients started clozapine treatment in Australia, and were registered with a mandatory monitoring service. We identified cases of myocarditis and cardiomyopathy from voluntary reports to the Australian Adverse Drug Reaction Committee and sought details of the relevant diagnostic studies, necropsies that had been done in suspicious cases, or both.Findings: 23 cases (20 men, three women, mean age 36 years [SD 9]) were identified: 15 of myocarditis and eight of cardiomyopathy associated with clozapine treatment. Six patients died. All cases of myocarditis (five deaths) occurred within 3 weeks of starting clozapine. Cardiomyopathy (one death) was diagnosed up to 36 months after clozapine was started. Necropsy results showed mainly eosinophilic infiltrates with myocytolysis, consistent with an acute drug reaction.Interpretation: Clozapine therapy may be associated with potentially fatal myocarditis and cardiomyopathy in physically healthy young adults with schizophrenia. [ABSTRACT FROM AUTHOR]

Whole prey diets are commonly used in the zoo and home setting for captive exotic and domestic cats, respectively. Despite their increase in popularity, nutrient digestibility of such diets has been poorly studied. In this study, the precision-fed cecectomized rooster assay was used to determine the protein quality and nitrogen-corrected true ME (TMEn) of 17 whole prey samples (mice [1 to 2, 10 to 13, 21 to 25, 30 to 40, and 150 to 180 d old], rats [1 to 4, 10 to 13, 21 to 25, 32 to 42, and >60 d old], rabbits [stillborn, 30 to 45 d old, and >65 d old], chicken [1 to 3 d old], and quail [1 to 3, 21 to 40, and >60 d old]) and 2 ground poultry-based products (chicken and duck). Amino acid score (AAS) and protein digestibility corrected AAS (PDCAAS) were calculated using the nutrient profile recommendations for domestic cat food as a reference value (AAFCO, 2012). Average individual indispensable AA (IAA) and total IAA (TIAA) digestibility coefficients were variable anddepended on AA (84 to 94% TIAA, 85 to 95% Arg, 87 to 96% His, 82 to 92% lie, 84 to 94% Leu, 85 to 93% Lys, 89 to 97% Met, 83 to 94% Phe, 80 to 95% Thr, 84 to 94% Trp, and 80 to 93% Val) and sample. For a majority of the whole prey items, AA concentrations were greater than the Association of American Feed Control Officials (AAFCO, 2012) domestic cat nutrient profile recommendations for growth and reproduction and adult maintenance; however, some whole prey had AA concentrations below the AAFCO (2012) recommendations: Met + Cys (1.10% DM) in ground duck (1.06% DM) and taurine (Tau; 0.20% DM) in 30-to-45- and >65-d-old rabbits (0.01 and 0.10% DM, respectively), 150-to-180-d-old mice (0.18% DM), and ground duck (0.15% DM). The TMEn (3.76 to 6.44 kcal/g DM) expressed as the percent of GE (i.e., TMEn/GE) ranged from 66 to 85%, demonstrating how variable the digestibility of these items may be and justifying more research in this area. Both Met and Tau are commonly added to commercial pet foods, so supplements are readily available to address potential deficiencies and improve protein quality. A direct comparison of the ME of whole prey items by in vivo feline and rooster experiments is needed. [ABSTRACT FROM AUTHOR]

This Second ESMO Consensus Conference on Lung Cancer article focuses on non-small-cell lung cancer pathology and molecular biomarkers.To complement the existing treatment guidelines for all tumour types, ESMO organises consensus conferences to focus on specific issues in each type of tumour. The Second ESMO Consensus Conference on Lung Cancer was held on 11–12 May 2013 in Lugano. A total of 35 experts met to address several questions on management of patients with non-small-cell lung cancer (NSCLC) in each of four areas: pathology and molecular biomarkers, early stage disease, locally advanced disease and advanced (metastatic) disease. For each question, recommendations were made including reference to the grade of recommendation and level of evidence. This consensus paper focuses on recommendations for pathology and molecular biomarkers in relation to the diagnosis of lung cancer, primarily non-small-cell carcinomas. [ABSTRACT FROM AUTHOR]

There has been a recent increase in the popularity of feeding unconventional diets, including whole prey diets, to domestic cats (Felis silvestris catus). Data are needed that allow animal caretakers to choose and formulate diets that meet the nutritional requirements of their cats. Our objective was to evaluate the effects of feeding 1- to 3-d-old whole chicks (WHO), ground adult chicken product (GRO), a chicken-based canned diet (CAN), and a chicken-based extruded diet (EXT) on apparent total tract energy and macronutrient digestibility, N balance, and blood metabolites of domestic cats (n = 11). Macronutrient, energy, and moisture concentrations of diets varied greatly (e.g., CP: 35 to 72% DM); however, cats fed all diets maintained BW and N balance. In general, cats fed WHO had lower nutrient digestibility than those fed CAN and EXT. Cats fed GRO had greater nutrient digestibility than cats fed commercial diets. For example, apparent OM and GE digestibility coefficients were greater (P ≤ 0.05) for cats fed CAN (86 and 88%, respectively), EXT (88 and 88%), and GRO (94 and 95%) compared with those fed WHO (83 and 83%) and greater (P ≤ 0.05) for cats fed GRO compared with those fed CAN and EXT. Many blood metabolites were modified by diet, but most remained within reference ranges for domestic cats. Serum cholesterol was elevated above the reference range for all treatments and greater (P ≤ 0.05) for cats fed WHO compared with those fed CAN, EXT, and GRO. Serum creatinine concentrations were above the reference range for all treatments and greater (P ≤ 0.05) for cats fed GRO compared with those fed CAN or WHO. These data indicate that the whole prey tested herein maintained short-term health and are adequately digestible for use in companion animal diets. Research is needed to determine the global and long-term health implications of feeding whole or ground diets to domestic cats, which may be different in terms of macronutrient, energy, and moisture profiles and nutrient digestibility. [ABSTRACT FROM AUTHOR]

What is known and objective The elderly are at increased risk of adverse effects resulting from drug interactions due to decreased drug clearance and polypharmacy. This study examines the prevalence of the co-administration of clinically relevant cytochrome P450 ( CYP) enzyme inhibitors with drugs that are substrates for these enzymes, in the community-dwelling elderly in Australia. Methods Participants aged 75 years or older ( n = 1045) were recruited via their general practitioners at four Australian sites (Newcastle, Sydney, Melbourne and Adelaide). A research nurse visited the home of each patient to compile a list of all prescription medications (including doses) currently used by the patient, and to complete assessments for depression, quality of life and cognitive status. The medication data were searched for the co-prescription of clinically relevant CYP inhibitor and corresponding substrate drugs. Results and discussion Potentially inappropriate CYP inhibitor-substrate combinations were found in 6·2% (65/1045) of patients. These patients were on significantly more medications (6·1 ± 3·0 vs. 3·9 ± 2·5; P = 0·001) and had a significantly lower physical quality of life ( P = 0·047) than those who were not on any CYP inhibitor-substrate combinations. The most commonly prescribed inhibitor-substrate combinations involved the CYP 3A4 inhibitors, diltiazem and verapamil, with the substrates simvastatin or atorvastatin. Only 1 of 41 patients on a CYP3A4 inhibitor and a statin was prescribed a non- CYP 3A4 metabolized statin. Metoprolol was another substrate commonly co-prescribed with a CYP2D6 inhibitor. In many cases, the risks and benefits of potential interactions may have been considered by the GP as the prescribed doses of both the inhibitor and substrate were relatively low. There were, however, some notable exceptions, also involving the substrates simvastatin, atorvastatin and metoprolol. There were no GP factors that were associated with co-prescription of CYP inhibitors and substrates. What is new and conclusion There is not a particular GP demographic that should be targeted for education regarding CYP interactions, but a focus on particular medications such as the statins may reduce the potential for clinically significant drug-drug interactions. As CYP drug-drug interactions are more common in patients on higher number of medications, particular vigilance is required at the time of prescribing and dispensing medications for elderly patients with multiple conditions. [ABSTRACT FROM AUTHOR]

There has been a recent increase in the feeding of unconventional diets, including whole-prey diets, to domestic pet cats. Our objective was to characterise faecal microbial populations of domestic cats fed whole and ground (6·35 mm grind) raw 1-3-d-old chicks (Rodent Pro). Faecal samples were collected from neutered male domestic cats (mean age = 5·7 years) fed these diet items in a crossover design. Bacterial DNA was isolated from faecal samples and amplicons of the 16S rRNA V4-V6 region were generated and analysed by 454 pyrosequencing. Faecal microbial populations of cats fed whole v. ground chicks did not differ. During the study, three cats presented with symptoms of infection (anorexia or diarrhoea) and tested clinically positive for Salmonella using a standard PCR method. The remaining cats tested negative. Data were analysed post hoc to test for differences in microbial populations due to clinical status. The predominant genera were Clostridium (9-30%), unidentified Lachnospiraceae (10-28%), Blautia (4-19%), Peptococcus (2-19%) and Fusobacterium (2-14%). Faeces of cats testing clinically positive for Salmonella had higher (P = 0·05) proportions of the genera Coprococcus (5·6 v. 0·4%) and Escherichia (subgenera Shigella; 1·1 v. 0·3%). Salmonella was not detected in faecal samples utilising the pyrosequencing method; however, there was a shift in microbial populations due to clinical status. The clinical symptoms reported herein may be not only due to the Salmonella itself, but also shifts in other gut microbial populations. [ABSTRACT FROM AUTHOR]

Extruded cat foods differ greatly in macronutrient distribution compared with wild-type diets (i.e. small mammals, reptiles, birds and insects). Based on the literature, this variability likely impacts faecal microbial populations. A completely randomised design was utilised to test the impacts of two dietary treatments on faecal microbial populations: (1) chicken-based extruded diet (EXT; n 3 cats) and (2) raw 1-3-d-old chicks (CHI; n 5 cats). Cats were adapted to diets for 10 d. Bacterial DNA was isolated from faecal samples and amplicons of the 16S rRNA V4-V6 region were generated and analysed by 454 pyrosequencing. Faeces of cats fed CHI had greater (P < 0·05) proportions of the following bacterial genera: unidentified Lachnospiraceae (15 v. 5%), Peptococcus (9 v. 3%) and Pseudobutyrivibrio (4 v. 1%). Faeces of cats fed EXT had greater (P < 0·05) proportions of Faecalibacterium (1·0 v. 0·2%) and Succinivibrio (1·2 v. < 0·1%). Five genera, including Lactobacillus and Bifidobacterium, were present in a majority of samples (two to three out of three) from cats fed EXT, but were not detected in the samples (zero of five) for cats fed CHI. These shifts in faecal bacterial populations compared with feeding a whole-prey diet may impact the functional capacities of the microbiota and its interaction with the host. Further research is warranted to determine the impacts of these shifts on long-term health of domestic cats. [ABSTRACT FROM AUTHOR]

Experimental and clinical investigations have confirmed the importance of dietary modifications in medical protocols designed to treat and prevent feline lower urinary tract signs (LUTS). The objective of this review is to discuss common medical conditions contributing to feline LUTS and to present currently used and potential preventative dietary modifications. Feline LUTS are a set of clinical conditions with similar symptoms related to inappropriate urine elimination due to a combination of genetics, stress and frustration reactions, environment, and medical condition or conditions, for example, idiopathic cystitis, urolithiasis, urethral obstruction, and urinary tract infection. The main goals of dietary modifications to prevent LUTS are 1) promote large dilute volumes of urine, 2) decrease the relative supersaturation of urine for specific stone types, and 3) promote healthy bacterial populations in the gastrointestinal and urogenital tracts. The impact of dietary composition, including dietary moisture, protein concentration and digestibility, mineral concentrations (i.e., Na, C1, Ca, P, and Mg), inclusion of acidifiers and alkalinizing agents, inclusion of vitamin B6, eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), and γ-linolenic acid, fiber concentration and characteristics, and oxalate degrading probiotics, on these outcomes is discussed, and dietary guidelines for cats are provided. Because of the complex interaction of diet composition, environment, and animal physiology, there is a need for clinical research linking current recommendations or dietary options for the treatment and prevention of LUTS with physiological outcomes (i.e., decreased relative supersaturation and LUTS recurrence). Additionally, for many recommendations (e.g., probiotic administration, EPA, DHA), extrapolation from other species was necessary. Research is needed in feline patients with LUTS on these dietary components. [ABSTRACT FROM AUTHOR]

Although dogs and cats are quite different than many livestock species in that they have evolved by eating diets high in fat and protein and low in carbohydrates, the gastrointestinal microbiota still play a key role in the gut and overall host health of these species. Early experiments in this field used culture-based techniques to evaluate the effects of dietary ingredients, such as fibers and prebiotics, on microbiota and indices of gut health (e.g., fecal scores, pH, fermentative end products). Such studies, however, were limited in scope and lacked precision as it pertained to the microbiota. The DNA-based techniques that have become available over the past decade have greatly upgraded research capabilities and have provided a more encompassing view of the canine and feline gastrointestinal microbiomes. High-throughput sequencing techniques that are much cheaper and faster than Sanger sequencing have been a key development in this progress. Sequence data not only allow for the identification of all microbial taxa but also provide information regarding functional capacity when a shotgun sequencing approach is used. The few canine and feline studies that have used 454 pyrosequencing have identified the predominant microbial taxa and metabolic functions present in healthy populations, differences between healthy and diseased dog and cat populations, and the effects of diet (e.g., dietary fibers, prebiotics, protein to carbohydrate ratio) on gastrointestinal microbiota. Although these studies have provided a foundation from which to work, more research is needed to increase our general understanding of the gastrointestinal microbiome, how it impacts host health, how its composition and activity may be altered by age, genetic, or environmental factors, and test whether specific pathogens or disease signatures can be identified and used in diagnosis and/or treatment of disease. [ABSTRACT FROM AUTHOR]

Little nutritional or metabolic infor-mation has been collected from captive exotic cats fed raw diets. In particular, fiber types and concentra-tions for use in raw meat-based diets for captive exotic felids have not been well studied. Our objective was to evaluate the effects of fiber type and concentration on apparent total tract energy and macronutrient digest-ibility, fecal characteristics, and fecal fermentative end-products in captive exotic felids. Four animals of each captive exotic species (jaguar (Panthera onca), cheetah (.Acinonyz jubatus), Malayan tiger (Panthera tigris corbetti), and Siberian tiger (Panthera tigris alta-ica) were randomized in four 4><4 Latin square designs (1 Latin square per species) to 1 of the 4 raw beef-based dietary treatments (94.7 to 96.7% beef trimmings): 2 or 4% cellulose or 2 or 4% beet pulp. Felid species, fiber type, and fiber concentration all impacted digest-ibility and fecal fermentative end-products. Inclusion of beet pulp increased (P < 0.05) fecal short-chain fatty acids and fecal output in all cats. Inclusion of 2 and 4% cellulose, and 4% beet pulp increased (P < 0.05) fecal bulk and diluted fecal branched-chain fatty acid concentrations compared with 2% beet pulp. Apparent total tract DM, OM, fat, and GE digestibility coeffi-cients decreased (P < 0.05) linearly with BW of cats. Additionally, fecal moisture, fecal score, and concentra-tions of fermentative end-products increased (P < 0.05) with BW. Although the response of many outcomes was dependent on cat size, in general, beet pulp increased wet fecal weight, fecal scores, and fecal metabolites, and reduced fecal pH. Cellulose generally reduced DM and OM digestibility, but increased dry fecal weight and fecal percent DM. Although beet pulp and cellu-lose fibers were tested individually in this study, these data indicate that the optimum fiber type and concentra-tion for inclusion in captive exotic felid diets is likely a combination of fermentable and nonfermentable fibers, with the optimal fiber blend being dependent on species. Smaller cats, such as cheetahs and jaguars, tol-erated fermentable fibers, whereas larger cats, such as Malayan and Siberian tigers, appeared to require more insoluble fibers that limit fermentation and provide fecal bulk. Further research is required to test whether these trends hold true when fed in combination. [ABSTRACT FROM AUTHOR]

Our objective was to evaluate raw meat diets for captive exotic and domestic carnivores con-taining traditional and alternative raw meat sources, specifically, beef trimmings, bison trimmings, elk muscle meat, and horse trimmings. We aimed to examine diet composition and protein quality; appar-ent total tract energy and macronutrient digestibility in domestic cats, African wildcats, jaguars, and Malayan tigers; and ME and fecal fermentative end-products in domestic cats. Because of variation in the meat sources, dietary proximate, AA, and long-chain fatty acid com-position were variable. Our analyses indicated that all diets had essential fatty acid deficiencies, and the elk diet (i.e., trimmed muscle meat) was deficient in total fat. Standardized AA digestibilities measured using the cecectomized rooster assay were high (>87%). Using the NRC minimum requirements for the growth of kittens, the first limiting AA of all diets was the com-bined requirement of Met and Cys (AA score: 81 to 95; protein digestibility corrected AA score: 75 to 90). All diets were highly digestible (88 to 89% OM digestibil-ity). There was no effect of diet or felid species on DM (85 to 87%), OM, and GE (90 to 91%) digestibilities. Apparent CP digestibility was greater (P < 0.05) in cats fed elk (97%) compared with those fed bison (96%), and greater (P < 0.05) in wildcats (97%) and domestic cats (97%) compared with tigers (95%). The diet and species interaction (P < 0.05) was observed for appar-ent fat digestibility. In domestic cats, the fresh fecal pH and proportions of acetate and butyrate were altered (P < 0.05) due to diet. Diet also affected (P < 0.05) fresh fecal concentrations of total branched-chain fatty acids, valerate, and Lactobacillus genus. In conclusion, although the raw meat diets were highly digestible, because of variation in raw meat sources the nutrient composition of the diets was variable. Thus, compo-sitional analysis of raw meat sources is necessary for proper diet formulation. The types of meat common-ly used in raw meat diets may be deficient in total fat (trimmed muscle meat) and essential fatty acids (trim-mings and muscle meats). Additionally, differences in raw meat source nutrient composition and digestibility affect the beneficial and putrefactive fermentative end-products found in feces. [ABSTRACT FROM AUTHOR]

The objectives of this study were to determine differences in apparent total tract energy and macronutrient digestibility, fecal and urine characteristics, and serum chemistry of domestic cats fed raw and cooked meat-based diets and extruded diet. Nine adult female domestic shorthair cats were utilized in a replicated 3 x 3 Latin square design. Dietary treatments included a high-protein extruded diet (EX; 57% CP), a raw beef-based diet (RB; 53% CP), and a cooked beef-based diet (GB; 52% CP). Cats were housed individually in metabolic cages and fed to maintain BW. The study consisted of three 21-d periods. Each period included diet adaptation during d 0 to 16; fecal and urine sample collections during d 17 to 20; and blood sample collection at d 21. Food intake was measured daily. Total feces and urine were collected for determination of nutrient digestibility. In addition, a fresh urine sample was collected from each cat for urinalysis, and a fresh fecal sample was collected from each cat for determination of DM percentage and ammonia, shortchain fatty acid (SCFA), and branched-chain fatty acid (BCFA) concentrations. All feces were scored after collection using a scale ranging from 1 (hard, dry pellets) to 5 (watery, liquid that can he poured). Blood was analyzed for serum metabolites. Apparent total tract DM, OM, CP, fat, and GE digestibilities were greater (P ⩽ 0.05) in cats fed RB and GB than those fed EX. Total fecal SCFA concentrations did not differ among dietary treatments; however, molar ratios of SCFA were modified by diet, with cats fed RB and GB having an increased (P ⩽ 0.05) proportion of fecal propionate and decreased (P ⩽ 0.05) proportion of fecal butyrate compared with cats fed EX. Fecal concentrations of ammonia, isobutyrate, valerate, isovalerate, and total BCFA were greater (P ⩽ 0.05) in cats fed EX compared with cats fed RB and GB. Our results indicated that cooking a raw meat diet does not alter apparent total tract energy and macronutrient digestibility and may also minimize risk of microbial contamination. Given the increasing popularity of feeding raw diets and the metabolic differences noted in this experiment, further research focused on the adequacy and safety of raw beef-based diets in domestic cats is justified. [ABSTRACT FROM AUTHOR]

Atypical adenomatous hyperplasia (AAH) has been suggested as the adenoma in an adenoma-carcinoma sequence in the lung periphery. From 1989-1998, we undertook a systematic, prospective search for AAH in lungs resected for cancer. AAH was found in 67 of 554 patients (12.1%) with primary lung carcinoma (9.2% in male patients and 19.0% in females). AAH was found in lungs bearing adenocarcinoma (23.2%) more frequently than with large cell undifferentiated carcinoma (12.5%) or squamous carcinoma (3.3%). A greater percentage of females with adenocarcinoma had AAH (30.2%) than did males with adenocarcinoma (18.8%). Numbers of AAH ranged from 1-42 per patient and more patients had small numbers of AAH, although 12 patients had 6 or more AAH foci. Larger numbers of AAH tended to be found in adenocarcinoma-bearing lungs. Ten of the 67 patients with AAH and primary lung carcinoma (15%) had multiple primary cancers (range 2-6), all of which were adenocarcinoma. Synchronous cancers were rare in lung tumour-bearing resections without AAH. Patients with AAH show no difference in post-operative survival to those without, for all stages of carcinoma and for Stage I disease alone. This study provides evidence for a strong association between atypical adenomatous hyperplasia and primary lung adenocarcinoma and lends weight to the AAH/adenoma-carcinoma hypothesis. [ABSTRACT FROM AUTHOR]

Aims To study immunohistochemically a group of 28 primary lung cancers which demonstrated histological features reminiscent of those characteristic of regression in malignant melanoma, to determine the phenotype of their immune cell infiltrates. Methods and results Using a standard s-ABC immunoperoxidase method then quantification by the Leica Q500 MC image analyser, the cellular infiltrate in these tumours, when compared to 67 control cases, showed excess CD3 + T-lymphocytes (P < 0.007), with an increase in CD4:CD8 ratio and increased CD68 + macrophages (P = 0.00001). CD57 + natural killer cells and S100 + Langerhans cells were also increased, but not quite significantly (P = 0.048 and P = 0.072, respectively). Conclusions This immunophenotype resembles that shown in regressing skin malignancies and suggests a similar process occurring in lung cancer. Regressing lung cancers are associated with a better prognosis than matched controls (P = 0.034), some showed radiological evidence of growth retardation and the group had an excess of the large cell undifferentiated histological type. [ABSTRACT FROM AUTHOR]

Existing evidence shows that hospital-acquired pressure ulcers lead to poor health outcomes and result in additional costs of up to $70,000 per patient because of high treatment costs and extended hospital stays. The incremental cost of pressure ulcers was determined by calculating the difference in average cost of pressure ulcer and non-pressure ulcer patients within each cluster. [Extracted from the article]

The temperature dependence of the EPR fine structure linewidths of (0.01 Gd, 0.99 Eu) (OH)3 monocrystals has been measured to study the dynamic interactions in this lattice. It is inferred from the complex behavior that static strain is the dominant linewidth broadening mechanism if T<85 K and that dynamic magnetic interactions dominate if 85 K

The article presents the author's views on foodborne diseases. The author states that changes in the way in which the food is produced have affected, and will continue to affect the epidemiology of foodborne infection. The author states that although biomedical research have improved the understanding and management of foodborne infections, food producers and retailers have to take measures to reduce or eliminate pathogens and consumers must also acknowledge their roles and responsibilities.

Reviewed: Railroads in the Age of Regulation, 1900-1980. Bryant, Keith L., Jr., ed.

Reviewed: Railroads in the Nineteenth Century. Frey, Robert L., ed.

We have surveyed the current state of telehealth in New Zealand. The survey found 22 telehealth projects active in 2003, compared with 12 identified in a previous survey in 2000. Many projects were small, localized and led by enthusiasts. Sustainability was a problem and many projects had failed to enter routine operation. Teleradiology and telepsychiatry services focused on acute hospitals were the most frequent clinical applications. The majority of projects (9 of the 22) were on the North Island, concentrated around Auckland. Telehealth appears to have special potential for rural communities and for the remote treatment (telecare) of chronic disease. However, the provision of telehealth in New Zealand is patchy and meets the same barriers to success as have been identified elsewhere, which make it difficult to move telehealth into routine operation. The obstacles constitute not so much a failure of individual projects as a lack of a driving force to take advantage of the opportunities. It is to be hoped that a suggested strategic framework can help to harness the opportunities. [ABSTRACT FROM AUTHOR]

The oxidative stress element of unhealthy scalp leads to compromised pre-emergent hair formation and poorly formed hair as it grows. Only cosmetic solutions can minimize the impact of unhealthy hair and to achieve healthy looking and feeling hair, the scalp health must be normalized first. The objectives of this research were to both investigate whether oxidative stress was a relevant aetiological element in scalp dandruff and seborrhoeic dermatitis and whether scalp condition affects the quality of hair that grows from it. Further, this research was designed to determine whether an effective anti-dandruff shampoo would repair and protect the scalp and pre-emergent hair from oxidative stress. This study demonstrated that oxidative stress is an aetiological element relevant to the dandruff condition and that a potentiated ZPT shampoo effectively improves scalp condition, including a reduction in oxidative stress. The compromised hair condition associated with dandruff is concomitantly improved when the scalp condition is improved. It appears that there is a direct link between hair quality and scalp health. [ABSTRACT FROM AUTHOR]

Reviewed: Regulating a New Economy: Public Policy and Economic Change in America, 1900-1933. Keller, Morton.

We observed survival after scheduled repair of abdominal aortic aneurysm in 1096 patients for a median ( IQR [range]) of 3.0 (1.5-5.8 [0-15]) years: 943 patients had complete data, 250 of whom died. We compared discrimination and calibration of an external model with the Kaplan-Meier model generated from the study data. Integrated Brier misclassification scores for both models at 1-5 postoperative years were 0.04, 0.08, 0.11, 0.13 and 0.16, respectively. Harrel's concordance index at 1-5 postoperative years was 0.73, 0.71, 0.68, 0.67 and 0.66, respectively. Groups with median 5-year predicted mortality of 40% (n = 251), 18% (n = 414) and 8% (n = 164) had lower observed mortality than 114 patients with 70% predicted mortality, hazard ratio (95% CI): 0.58 (0.37-0.76), p = 0.0031; 0.30 (0.19-0.48), p = 1.7 × 10−12 and 0.19 (0.13-0.27), p = 1.3 × 10−10, respectively, test for trend p = 5.6 × 10−15. Survival predicted by the external calculator was similar to the Kaplan-Meier estimate. [ABSTRACT FROM AUTHOR]

Background: Neoadjuvant or adjuvant chemotherapy confers a modest benefit over surgery alone for resectable non-small-cell lung cancer (NSCLC). In early-phase trials, nivolumab-based neoadjuvant regimens have shown promising clinical activity; however, data from phase 3 trials are needed to confirm these findings.Methods: In this open-label, phase 3 trial, we randomly assigned patients with stage IB to IIIA resectable NSCLC to receive nivolumab plus platinum-based chemotherapy or platinum-based chemotherapy alone, followed by resection. The primary end points were event-free survival and pathological complete response (0% viable tumor in resected lung and lymph nodes), both evaluated by blinded independent review. Overall survival was a key secondary end point. Safety was assessed in all treated patients.Results: The median event-free survival was 31.6 months (95% confidence interval [CI], 30.2 to not reached) with nivolumab plus chemotherapy and 20.8 months (95% CI, 14.0 to 26.7) with chemotherapy alone (hazard ratio for disease progression, disease recurrence, or death, 0.63; 97.38% CI, 0.43 to 0.91; P = 0.005). The percentage of patients with a pathological complete response was 24.0% (95% CI, 18.0 to 31.0) and 2.2% (95% CI, 0.6 to 5.6), respectively (odds ratio, 13.94; 99% CI, 3.49 to 55.75; P<0.001). Results for event-free survival and pathological complete response across most subgroups favored nivolumab plus chemotherapy over chemotherapy alone. At the first prespecified interim analysis, the hazard ratio for death was 0.57 (99.67% CI, 0.30 to 1.07) and did not meet the criterion for significance. Of the patients who underwent randomization, 83.2% of those in the nivolumab-plus-chemotherapy group and 75.4% of those in the chemotherapy-alone group underwent surgery. Grade 3 or 4 treatment-related adverse events occurred in 33.5% of the patients in the nivolumab-plus-chemotherapy group and in 36.9% of those in the chemotherapy-alone group.Conclusions: In patients with resectable NSCLC, neoadjuvant nivolumab plus chemotherapy resulted in significantly longer event-free survival and a higher percentage of patients with a pathological complete response than chemotherapy alone. The addition of nivolumab to neoadjuvant chemotherapy did not increase the incidence of adverse events or impede the feasibility of surgery. (Funded by Bristol Myers Squibb; CheckMate 816 ClinicalTrials.gov number, NCT02998528.). [ABSTRACT FROM AUTHOR]

The European Society for Medical Oncology (ESMO) held a virtual consensus-building process on epidermal growth factor receptor (EGFR)-mutant non-small-cell lung cancer in 2021. The consensus included a multidisciplinary panel of 34 leading experts in the management of lung cancer. The aim of the consensus was to develop recommendations on topics that are not covered in detail in the current ESMO Clinical Practice Guideline and where the available evidence is either limited or conflicting. The main topics identified for discussion were: (i) tissue and biomarkers analyses; (ii) early and locally advanced disease; (iii) metastatic disease and (iv) clinical trial design, patient's perspective and miscellaneous. The expert panel was divided into four working groups to address questions relating to one of the four topics outlined above. Relevant scientific literature was reviewed in advance. Recommendations were developed by the working groups and then presented to the entire panel for further discussion and amendment before voting. This manuscript presents the recommendations developed, including findings from the expert panel discussions, consensus recommendations and a summary of evidence supporting each recommendation. • A virtual consensus on the management of EGFR-mutant NSCLC was organized by the ESMO, including 34 experts from 18 countries. • The experts compiled recommendations with supporting evidence on controversial topics about the EGFR-mutant lung cancer. • Recommendations were formulated for tissue and biomarkers analyses; early, locally advanced and metastatic disease; miscellaneous. [ABSTRACT FROM AUTHOR]

With the continued rise in feline obesity, novel weight management strategies are needed. To date, strategies aimed at altering physical activity, an important factor in weight maintenance, have been lacking. Photoperiod is known to cause physiological changes in seasonal mammals, including changes in body weight ( BW) and reproductive status. Thus, our objective was to determine the effect of increased photoperiod (longer days) on voluntary physical activity levels, resting metabolic rate ( RMR), food intake required to maintain BW, and fasting serum leptin and ghrelin concentrations in adult cats. Eleven healthy, adult, neutered, male domestic shorthair cats were used in a randomized crossover design study. During two 12-week periods, cats were exposed to either a short-day ( SD) photoperiod of 8 h light: 16 h dark or a long-day ( LD) photoperiod of 16 h light: 8 h dark. Cats were fed a commercial diet to maintain baseline BW. In addition to daily food intake and twice-weekly BW, RMR (via indirect calorimetry), body composition [via dual-energy X-ray absorptiometry ( DEXA)] and physical activity (via Actical activity monitors) were measured at week 0 and 12 of each period. Fasting serum leptin and ghrelin concentrations were measured at week 0, 6 and 12 of each period. Average hourly physical activity was greater (p = 0.008) in LD vs. SD cats (3770 vs. 3129 activity counts/h), which was primarily due to increased (p < 0.001) dark period activity (1188 vs. 710 activity counts/h). This corresponded to higher (p < 0.0001) daily metabolizable energy intake (mean over 12-week period: 196 vs. 187 kcal/day), and increased (p = 0.048) RMR in LD cats (9.02 vs. 8.37 kcal/h). Body composition, serum leptin and serum ghrelin were not altered by photoperiod. More research is needed to determine potential mechanisms by which these physiological changes occurred and how they may apply to weight management strategies. [ABSTRACT FROM AUTHOR]

Oxytocin is known to play important roles in uterine contractions, mediated at least in part by increasing intracellular Ca2+ concentration ([Ca2+]i), through enhancing extracellular Ca2+ entry and Ca2+ release from the sarcoplasmic reticulum, processes that are intimately linked with mitochondria. This study examined the effects of oxytocin on mitochondrial function. This was achieved by measuring the ratiometric JC-1 fluorescence signal in isolated myometrial cells, which provides a relative measure of the mitochondrial membrane potential (ψ m), and also by loading the cells with Oregon Green BAPTA-AM to examine changes in [Ca2+]i. Oxytocin (1 n m) depolarized the ψ m to 73.8 ± 3.7% of the control value ( P < 0.05; perfused for 11 min) and also caused a transient increase in [Ca2+]i. The depolarization of mitochondrial membrane potential was effectively reversed by 2-aminoethoxydiphenyl borate, nifedipine, Ca2+-free solution or oligomycin, with the ratiometric JC-1 fluorescence signal becoming no different from the control value in all cases (i.e. P > 0.05). The reduction in ψ m is likely to occur at least in part through the oxytocin-induced increase in [Ca2+]i, causing enhanced mitochondrial uptake of Ca2+ and resultant dissipation of the mitochondrial electrochemical gradient. ATP synthase is also stimulated, which would further contribute to a decrease in ψ m. [ABSTRACT FROM AUTHOR]