ALLIANCE A022104/NRG-GI010: The Janus Rectal Cancer Trial: a randomized phase II/III trial testing the efficacy of triplet versus doublet chemotherapy regarding clinical complete response and disease-free survival in patients with locally advanced rectal cancer.

Background: Recent data have demonstrated that in locally advanced rectal cancer (LARC), a total neoadjuvant therapy (TNT) approach improves compliance with chemotherapy and increases rates of tumor response compared to neoadjuvant chemoradiation (CRT) alone. They further indicate that the optimal sequencing of TNT involves consolidation (rather than induction) chemotherapy to optimize complete response rates. Data, largely from retrospective studies, have also shown that patients with clinical complete response (cCR) after neoadjuvant therapy may be managed safely with the watch and wait approach (WW) instead of preemptive total mesorectal resection (TME). However, the optimal consolidation chemotherapy regimen to achieve cCR has not been established, and a randomized clinical trial has not robustly evaluated cCR as a primary endpoint. Collaborating with a multidisciplinary oncology team and patient groups, we designed this NCI-sponsored study of chemotherapy intensification to address these issues and to drive up cCR rates, to provide opportunity for organ preservation, improve quality of life for patients and improve survival outcomes. Methods: In this NCI-sponsored multi-group randomized, seamless phase II/III trial (1:1), up to 760 patients with LARC, T4N0, any T with node positive disease (any T, N+) or T3N0 requiring abdominoperineal resection or coloanal anastomosis and distal margin within 12 cm of anal verge will be enrolled. Stratification factors include tumor stage (T4 vs T1-3), nodal stage (N+ vs N0) and distance from anal verge (0-4; 4-8; 8-12 cm). Patients will be randomized to receive neoadjuvant long course chemoradiation (LCRT) followed by consolidation doublet (mFOLFOX6 or CAPOX) or triplet chemotherapy (mFOLFIRINOX) for 3-4 months. LCRT in both arms involves 4500 cGy in 25 fractions over 5 weeks + 900 cGy boost in 5 fractions with a fluoropyrimidine (capecitabine preferred). Patients will undergo assessment 8-12 (+/- 4) weeks post-TNT completion. The primary endpoint for the phase II portion will compare cCR between treatment arms. A total number of 296 evaluable patients (148 per arm) will provide statistical power of 90.5% to detect an 17% increase in cCR rate, at a one-sided alpha=0.048. The primary endpoint for the phase III portion will compare disease-free survival (DFS) between treatment arms. A total of 285 DFS events will provide 85% power to detect an effect size of hazard ratio 0.70 at a one-sided alpha of 0.025, requiring enrollment of 760 patients (380 per arm). Secondary objectives include time-to event outcomes (overall survival, organ preservation time and time to distant metastasis) and adverse effects. Biospecimens including archival tumor tissue, plasma and buffy coat in EDTA tubes, and serial rectal MRIs will be collected for exploratory correlative research. This study, activated in late 2022, is open across the NCTN and has a current accrual of 312. Support: U10CA180821, U10CA180882, U24 CA196171; https://acknowledgments.alliancefound.org . Discussion: Building off of data from modern day rectal cancer trials and patient input from national advocacy groups, we have designed the current trial studying chemotherapy intensification via a consolidation chemotherapy approach with the intent to enhance cCR and DFS rates, increase organ preservation rates, and improve quality of life for patients with rectal cancer. Trial Registration: Clinicaltrials.gov ID: NCT05610163 ; Support includes U10CA180868 (NRG) and U10CA180888 (SWOG).

Identification of prognostic factors for survival in patients with metastatic gastric adenocarcinoma in a Mexican population.

INTRODUCTION AND AIMS: Gastric adenocarcinoma is among the high-ranking tumors, with respect to frequency and mortality, worldwide. The inflammatory process and immune system activity are associated with oncologic control. Our aim was to identify whether the neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and other variables are prognostic factors for survival in patients with metastatic gastric cancer in a Mexican population. MATERIAL AND METHODS: Patients diagnosed with metastatic gastric adenocarcinoma, hospitalized within the time frame of December 2011 to 2021, were analyzed. The NLR, PLR, and albumin and hemoglobin levels obtained from blood samples were calculated. Functional status (ECOG and Karnofsky), sex, histology, and the presence of signet ring cells were also considered possible prognostic factors. Each factor's prognostic value for overall survival was determined through univariate and multivariate analyses. RESULTS: The study included 956 patients diagnosed with metastatic gastric cancer, of whom 494 (51.7%) were men and 462 (48.3%) were women. The main histologic finding was diffuse adenocarcinoma (n = 619, 64.7%), followed by intestinal adenocarcinoma (n = 293, 30.6%), and the presence of signet ring cells was found in 659 (68.9%) patients. Diagnostic laparoscopy was performed on 238 patients (24.9%) to confirm peritoneal carcinomatosis. The multivariate analysis showed that an NLR above 3.2 (HR 1.51, 95% CI 1.27-1.8; p < 0.001), albumin below 3.5 g/dl (HR 1.25, CI 1.06-1.47; p = 0.006), and an ECOG performance status of 2 or higher (HR 1.39, CI 1.10-1.76; p = 0.005) were independent factors that predicted a lower survival rate, whereas a Karnofsky score above 70% (HR 0.69, CI 0.53-0.91; p = 0.008) was associated with a better survival rate. Lastly, the PLR was not statistically significant in the multivariate analysis. CONCLUSIONS: The NLR, nutritional status assessed through albumin measurement, and functional status can act as independent prognostic survival factors in hospitalized Mexican patients diagnosed with metastatic gastric adenocarcinoma and be taken into account during therapeutic decision-making.

Quality of life and clinical outcomes in rectal cancer patients treated on a 1.5T MR-Linac within the MOMENTUM study.

Background and purpose: This study assessed quality of life (QoL) and clinical outcomes in rectal cancer patients treated with magnetic resonance (MR) guided short-course radiation therapy (SCRT) on a 1.5 Tesla (T) MR-Linac during the first 12 months after treatment. Materials and methods: Rectal cancer patients treated with 25 Gy SCRT in five fractions with curative intent in the Netherlands (2019-2022) were identified in MOMENTUM (NCT04075305). Toxicity (CTCAE v5) and QoL (EORTC QLQ-C30 and -CR29) was primarily analyzed in patients without metastatic disease (M0) and no other therapies after SCRT. Patients who underwent tumor resection were censored from surgery. A generalized linear mixed-model was used to investigate clinically meaningful (≥10) and significant (P < 0.05) QoL changes. Clinical and pathological complete response (cCR and pCR) rates were calculated in patients in whom response was documented. Results: A total of 172 patients were included, of whom 112 patients were primarily analyzed. Acute and late radiation-induced high-grade toxicity were reported in one patient, respectively. CCR was observed in 8/64 patients (13 %), 14/37 patients (38 %) and 13/16 patients (91 %) at three, six and twelve months; pCR was observed in 3/69 (4 %) patients. After 12 months, diarrhea (mean difference [MD] -17.4 [95 % confidence interval [CI] -31.2 to -3.7]), blood and mucus in stool (MD -31.1 [95 % CI -46.4 to -15.8]), and anxiety (MD -22.4 [95 % CI -34.0 to -10.9]) were improved. Conclusion: High-field MR-guided SCRT for the treatment of patients with rectal cancer is associated with improved disease-related symptom management and functioning one year after treatment.

Army ant middens - Home and nursery of a diverse beetle fauna.

Army ants provide nourishment to a large variety of animals. This includes birds that feed on animals flushed out by army ant raids, symbiotic arthropods that consume the ants' prey or their brood, and other arthropods that scavenge on army ant refuse deposits. The latter have not received much attention, and the few published studies lack detailed species identifications. Here we provide a first systematic inventory of the beetle fauna associated with refuse deposits of Eciton army ants, with a focus on Eciton burchellii. We collected 8364 adult beetles, 511 larvae, and 24 eggs from 34 deposits at La Selva Biological Station, Costa Rica. We used a combination of DNA barcoding and morphology to identify a subset of 436 specimens to species level. The samples included several new species, and we here formally describe two water scavenger beetles (Hydrophilidae). Refuse deposits harbored a diverse beetle fauna. The identified subset consisted of 91 beetle species from 12 families, with rove beetles being the most abundant and diverse visitors. Of the 85 species found with E. burchellii, 50 species were collected from only one or two refuse deposits. Conversely, seven species were found in 10 or more refuse deposits, indicating a certain level of habitat specialization. We matched adults and immatures for 22 beetle species via DNA barcodes, demonstrating that army ant middens also serve as a beetle nursery. The present survey highlights the significant ecological function of army ants as promoters of biodiversity and their status as keystone species in tropical rainforests.

Hiding in plain sight: Cryptic enemies are found on cochineal (Hemiptera: Dactylopiidae), a scale insect of economic and cultural significance.

Cochineal is the common name for cactus-feeding scale insects in the Dactylopiidae. These ruby-red insects include the domesticated dye insect Dactylopius coccus. Dactylopius coccus and congeners have been introduced around the world, some accidentally, to become pests of prickly pear cactus species (Opuntia), and some intentionally, for dye production or biological control of pest Opuntia. In the northern Sonoran Desert (Tucson, AZ, USA), we studied the enemy complex of D. opuntiae and D. confusus on Opuntia and characterized two cryptic enemies, a coccinellid beetle predator and a parasitoid wasp. (1) Hyperaspis sp. The coccinellid predator Hyperaspis trifurcata shares a niche with a similar, typically all-black beetle. Morphological data, crossing tests, and phylogenetic results showed the black beetle to be a distinct, undescribed species in the genus Hyperaspis, with a rare spotted phenotype that is similar in appearance to H. trifurcata. Crossing tests among black and spotted forms showed the spotted morph is inherited as a single-locus dominant allele. (2) Formicencyrtus thoreauini. Rearing of this ant-like parasitoid wasp (Encyrtidae) in pure culture of D. opuntiae showed it to be a semi-gregarious primary parasitoid of cochineal. To our knowledge, this is the first confirmed instance of a cochineal parasitoid. Observations of development show early instar larvae keep their posterior end within the egg chorion, attached to an aeroscopic plate with a connection to the cochineal body wall. Late instar larvae are eventually surrounded by a membrane, likely of larval origin. Wasps then pupate in a dry air-filled chamber within the desiccated scale remains before chewing out as an adult. Both Hyperaspis sp. and F. thoreauini may have restricted distributions. Hyperaspis sp. does not appear to be a member of the cochineal community in Mexico or Texas, and scant records suggest F. thoreauini may also be restricted to the Southwestern USA.

Technical Radiotherapy Advances - The Role of Magnetic Resonance Imaging-Guided Radiation in the Delivery of Hypofractionation.

Safe delivery of hypofractionated radiotherapy requires high levels of accuracy due to the high doses of radiation delivered per fraction. Magnetic resonance guided radiotherapy (MRgRT) represents a new treatment paradigm which allows improved visualisation of targets and organs at risk, alongside the capability to adapt the treatment plan in real time prior to treatment delivery. There are challenges to delivering hypofractionated radiotherapy with conventional image-guided radiotherapy (IGRT) techniques and MRgRT may help to improve accuracy in radiation delivery in a number of clinical and anatomical scenarios. Specifically, there is an emerging role of MRgRT in delivering stereotactic body radiotherapy (SBRT) for locally advanced pancreatic cancer (LAPC) due to the superior soft tissue contrast provided by Magnetic Resonance Imaging combined with the ability to accommodate variation in anatomical appearances during treatment delivery. Reported data on the use of MRgRT in LAPC and it's role in enabling dose escalation are discussed in this article. There are further potential benefits to the use of MRgRT, for example the use of functional imaging during treatment delivery and generation of synthetic computed tomography, which have previously been impractical or unachievable. The overall aim of this article is to demonstrate the utility of MRgRT in facilitating safe delivery of hypofractionated radiotherapy and to highlight ways in which it may help to overcome challenges posed by current IGRT techniques.

A remarkable legion of guests: Diversity and host specificity of army ant symbionts.

Tropical rainforests are among the most diverse biomes on Earth. While species inventories are far from complete for any tropical rainforest, even less is known about the intricate species interactions that form the basis of these ecological communities. One fascinating but poorly studied example are the symbiotic associations between army ants and their rich assemblages of parasitic arthropod guests. Hundreds of these guests, or myrmecophiles, have been taxonomically described. However, because previous work has mainly been based on haphazard collections from disjunct populations, it remains challenging to define species boundaries. We therefore know little about the species richness, abundance and host specificity of most guests in any given population, which is crucial to understand co-evolutionary and ecological dynamics. Here, we report a quantitative community survey of myrmecophiles parasitizing the six sympatric Eciton army ant species in a Costa Rican rainforest. Combining DNA barcoding with morphological identification of over 2,000 specimens, we discovered 62 species, including 49 beetles, 11 flies, one millipede and one silverfish. At least 14 of these species were new to science. Ecological network analysis revealed a clear signal of host partitioning, and each Eciton species was host to both specialists and generalists. These varying degrees in host specificities translated into a moderate level of network specificity, highlighting the system's level of biotic pluralism in terms of biodiversity and interaction diversity. By providing vouchered DNA barcodes for army ant guest species, this study provides a baseline for future work on co-evolutionary and ecological dynamics in these species-rich host-symbiont networks across the Neotropical realm.

Is transportation a risk factor for African swine fever transmission in Australia: a review.

African swine fever (ASF) is a viral disease of the pigs that was first described in Africa during the early part of the twentieth century. The disease has periodically occurred outside of Africa, including an ongoing epidemic in Europe and Asia that started in 2007; the disease has never occurred in Australia or New Zealand. Once introduced into a country, spread can occur through direct and indirect routes of transmission. Infected feral pig populations have the potential to act as a long-term reservoir for the virus, making eradication difficult. Just before and throughout the period of clinical signs, ASF virus is shed in oronasal fluids, urine, faeces and blood. This results in contamination of the pig's environment, including flooring, equipment and vehicles. Transportation-related risk factors therefore are likely to play an important role in ASF spread, though evidence thus far has been largely anecdotal. In addition to the existing AUSVETPLAN ASF plan, efforts should be made to improve transportation biosecurity, from the time a pig leaves the farm to its destination. Collection of data that could quantify the capabilities and capacity of Australia to clean and disinfect livestock trucks would help to determine if private and/or public sector investment should be made in this area of biosecurity. No peer-reviewed research was identified that described a specific process for cleaning and disinfecting a livestock truck known to be contaminated with ASF virus, though literature suggests that transportation is an important route of transmission for moving the virus between farms and countries.

African swine fever: a New Zealand perspective on epidemiological risk factors for its occurrence.

This article reviews key epidemiological and clinical features of African swine fever (ASF). We identify particular aspects of New Zealand's pig populations (commercial, non-commercial, and wild) that may affect the risk of disease entry or spread. Review of published literature is supplemented by analysis of demographic and spatial aspects of the New Zealand commercial, non-commercial, and feral pig populations to provide context around risk factors for the disease that are most relevant to New Zealand. The current Eurasian outbreak of ASF, including recent spread into Oceania, has increased the risk of an incursion of the disease into New Zealand. Large volumes of fresh pork importation (including from countries affected by ASF), large non-commercial pig populations with substantial spatial overlap with the country's commercial industry, limited monitoring of compliance with waste food feeding regulations, and lack of mandatory premises identification for non-commercial pig holdings would likely contribute to the risk of spread of ASF in the event of an incursion. Awareness amongst veterinarians of these risk factors will contribute to national biosecurity and disease preparedness efforts in New Zealand.

A systematic review of in vitro studies evaluating the inhibitory effects of polyphenol-rich fruit extracts on carbohydrate digestive enzymes activity: a focus on culinary fruits consumed in Europe.

Evidence shows that polyphenols can attenuate postprandial blood glucose responses to meals containing digestible carbohydrate. Polyphenol-rich plant extracts are emerging as potential ingredients in functional foods and/or beverages despite limited understanding of their physiological effects. Many studies have investigated the mechanisms of polyphenol-rich fruit extracts on inhibition of digestive enzymes. However, the evidence available has yet to be critically evaluated systematically. This report reviews the in vitro literature to quantify the effect of fruit polyphenol extracts on the activities of digestive carbohydrases. A systematic literature search was conducted using six science databases. Included studies, totaling 34 in number, were in vitro digestion models which quantified gut digestive enzyme(s) activity on starch digestion in the presence of fruit polyphenol extracts. Most studies assessed the effects of fruit extracts on either α-amylase (n = 30) or α-glucosidase (n = 30) activity. Studies were consistent overall in showing stronger inhibition of α-amylase compared to α-glucosidase by proanthocyanidin- and/or ellagitannin-rich fruit extracts. Recommendations are proposed for future reporting of this type of research to enable meaningful synthesis of the literature as a whole. Such knowledge could allow effective choices to be made for development of novel functional foods and beverages.

Assessment and treatment of pediatric behavioral sleep disorders in Canada.

OBJECTIVES/BACKGROUND: This paper outlines the current state of Canadian training, clinical services, research, and advocacy initiatives related to non-respiratory sleep disorders, with a specific focus on insomnia, the most common sleep problem in children. METHODS: Information for this narrative review was collected from peer-reviewed publications, web-resources, and personal communications and experiences. RESULTS: It is estimated that approximately one-third of Canadian children and youth present with insomnia, and that this is impacting their physical and mental health, as well as learning in school. Training in pediatric sleep is limited and highly inconsistent within and across disciplines. While there are some publicly and privately funded pediatric sleep services available, these are mostly focused on respiratory sleep problems and are not equally accessible across the country. CONCLUSIONS: Pediatric assessment and treatment services for non-respiratory sleep disorders needs to be more integrated into the Canadian health care system.

First isolation of West Nile virus in Zambia from mosquitoes.

Mosquito surveillance studies to identify mosquito-borne flaviviruses have identified West Nile Virus (WNV) for the first time in Zambia. The Zambian WNV isolate from Culex quinquefasciatus mosquitoes collected in the Western Province was closely related genetically to WNV lineage 2 South African strains which have been previously shown to be highly neuroinvasive. These data provide the first evidence of the circulation of WNV in Zambia and suggest there should be an increased awareness of possible associated human and animal diseases in that country.

What are interesterified fats and should we be worried about them in our diet?

Interesterified (IE) fats are used in a wide range of food products and were introduced as a replacement for trans fats, which are known to be detrimental to cardiovascular health. However, the effects of interesterification on metabolism and subsequent effects on cardiovascular health are not understood and previous studies have seldom investigated industrially-relevant IE fats. No legislation currently exists regarding the labelling of IE fats in food products and therefore estimates of average consumption rates in the UK population are currently unavailable. In order to meet the urgent need for a systematic investigation of the health effects of consumer-relevant IE fats, it is essential to estimate current IE fat intakes and to investigate biological mechanisms that might mediate acute and chronic cardiometabolic effects of commercially relevant IE fats.

The future for long chain n-3 PUFA in the prevention of coronary heart disease: do we need to target non-fish-eaters?

Dietary guidelines in many countries include a recommendation to consume oily fish, mainly on the basis of evidence from prospective cohort studies that fish consumption is cardioprotective. However, average intakes are very low in a large proportion of the UK population. Some groups, such as vegans and vegetarians, purposely omit fish (along with meat) from their diet resulting in zero or trace intakes of long chain (LC) n-3 PUFA. Although the efficacy of dietary fish oil supplementation in the prevention of CVD has been questioned in recent years, the balance of evidence indicates that LC n-3 PUFA exert systemic pleiotropic effects through their influence on gene expression, cell signalling, membrane fluidity and by conversion to specialised proresolving mediators; autacoid lipid mediators that resolve inflammatory events. The long-term impact of reduced tissue LC n-3 PUFA content on cardiovascular health is surprisingly poorly understood, particularly with regard to how low proportions of LC n-3 PUFA in cell membranes may affect cardiac electrophysiology and chronic inflammation. Randomised controlled trials investigating effects of supplementation on prevention of CHD in populations with low basal LC n-3 PUFA tissue status are lacking, and so the clinical benefits of supplementing non-fish-eating groups with vegetarian sources of LC n-3 PUFA remain to be determined. Refocusing dietary LC n-3 PUFA intervention studies towards those individuals with a low LC n-3 PUFA tissue status may go some way towards reconciling results from randomised controlled trials with the epidemiological evidence.

A qualitative study of overweight and obese Australians' views of food addiction.

The concept of food addiction is increasingly used in the academic literature and popular media to explain some forms of overweight and obesity. However, there is limited evidence on how this term is understood by and impacts overweight and obese individuals. This qualitative study investigated the views of overweight and obese individuals on food addiction, and its likely impact upon stigma, treatment-seeking, and support for public policies to reduce overeating. Semi-structured interviews were conducted with 23 overweight and obese individuals (Mage = 38, MBMI = 33, 74% female) and analysed thematically. The concept of food addiction was consistent with many participants' personal experiences, and was accompanied by high perceptions of control and personal responsibility. Some participants believed "sugar" or "fat" addiction to be more accurate. Others were reluctant to be described as an "addict" owing to perceived negative connotations and the belief that it would increase self-stigma. Food addiction was seen as a motivator for seeking psychological services, but not pharmaceutical or surgical treatments. In light of food addiction being perceived as plausible and relevant, participants supported targeted public health policies (e.g., taxes, regulations for junk food container sizes) but did not believe these would affect their own purchasing or consumption behaviours. Education for interpreting food labels and reducing the costs of healthy foods were endorsed, leading to positive changes in food-related behaviours. This research suggests discretionary use of the food addiction label in a supportive and educational manner to minimise stigma while encouraging treatment-seeking.

Recommendations for MRI-based contouring of gross tumor volume and organs at risk for radiation therapy of pancreatic cancer.

PURPOSE: Local recurrence is a common and morbid event in patients with unresectable pancreatic adenocarcinoma. A more conformal and targeted radiation dose to the macroscopic tumor in nonmetastatic pancreatic cancer is likely to reduce acute toxicity and improve local control. Optimal soft tissue contrast is required to facilitate delineation of a target and creation of a planning target volume with margin reduction and motion management. Magnetic resonance imaging (MRI) offers considerable advantages in optimizing soft tissue delineation and is an ideal modality for imaging and delineating a gross tumor volume (GTV) within the pancreas, particularly as it relates to conformal radiation planning. Currently, no guidelines have been defined for the delineation of pancreatic tumors for radiation therapy treatment planning. Moreover, abdominal MRI sequences are complex and the anatomy relevant to the radiation oncologist can be challenging. The purpose of this study is to provide recommendations for delineation of GTV and organs at risk (OARs) using MRI and incorporating multiple MRI sequences. METHODS AND MATERIALS: Five patients with pancreatic cancer and 1 healthy subject were imaged with MRI scans either on 1.5T or on 3T magnets in 2 separate institutes. The GTV and OARs were contoured for all patients in a consensus meeting. RESULTS: An overview of MRI-based anatomy of the GTV and OARs is provided. Practical contouring instructions for the GTV and the OARs with the aid of MRI were developed and included in these recommendations. In addition, practical suggestions for implementation of MRI in pancreatic radiation treatment planning are provided. CONCLUSIONS: With this report, we attempt to provide recommendations for MRI-based contouring of pancreatic tumors and OARs. This could lead to better uniformity in defining the GTV and OARs for clinical trials and in radiation therapy treatment planning, with the ultimate goal of improving local control while minimizing morbidity.

Lack of effect of supplementation with EPA or DHA on platelet-monocyte aggregates and vascular function in healthy men.

BACKGROUND AND AIMS: Eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) found in fish oil are postulated to have favourable effects on platelet, endothelial and vascular function. We investigated whether EPA has differential effects on in vivo platelet aggregation and other markers of cardiovascular risk compared to DHA. METHODS AND RESULTS: Following a 2 wk run-in taking encapsulated refined olive oil, 48 healthy young men were randomly allocated using a parallel design to receive EPA-rich (3.1 g EPA/d) or DHA-rich (2.9 g DHA/d) triglyceride concentrates or refined olive oil (placebo), for a total supplementary lipid intake of 5 g/d. The specified primary outcome was change in platelet monocyte aggregates (PMA); secondary outcomes were capillary density, augmentation index, digital pulse volume measurements, 24 h ambulatory BP, plasma 8-isoprostanes-F2α. Changes in the proportions of DHA and EPA in erythrocytes and non-esterified fatty acid composition indicated compliance to the intervention. There was no significant treatment effect on PMA (P = 0.382); mean changes (%) (95% CI) were placebo -0.5 (-2.0, 1.04), EPA 0.4 (-0.8, 1.6), DHA 0.3 (-1.5, 2.0). R-QUICKI, an index of insulin sensitivity, was greater following EPA compared to placebo (P < 0.05). No other significant differences were noted. CONCLUSION: Neither EPA- nor DHA-rich fish oil supplementation influence platelet-monocyte aggregation or several markers of vascular function after 6 wk in healthy young males. This trial was registered at clinicaltrials.gov as NCT01735357.

Which adolescents develop persistent substance dependence in adulthood? Using population-representative longitudinal data to inform universal risk assessment.

BACKGROUND: To our knowledge, there are no universal screening tools for substance dependence that (1) were developed using a population-based sample, (2) estimate total risk briefly and inexpensively by incorporating a relatively small number of well-established risk factors, and (3) aggregate risk factors using a simple algorithm. We created a universal screening tool that incorporates these features to identify adolescents at risk for persistent substance dependence in adulthood. METHOD: Participants were members of a representative cohort of 1037 individuals born in Dunedin, New Zealand in 1972-1973 and followed prospectively to age 38 years, with 95% retention. We assessed a small set of childhood and adolescent risk factors: family history of substance dependence, childhood psychopathology (conduct disorder, depression), early exposure to substances, frequent substance use in adolescence, sex, and childhood socioeconomic status. We defined the outcome (persistent substance dependence in adulthood) as dependence on one or more of alcohol, tobacco, cannabis, or hard drugs at ⩾3 assessment ages: 21, 26, 32, and 38 years. RESULTS: A cumulative risk index, a simple sum of nine childhood and adolescent risk factors, predicted persistent substance dependence in adulthood with considerable accuracy (AUC = 0.80). CONCLUSIONS: A cumulative risk score can accurately predict which adolescents in the general population will develop persistent substance dependence in adulthood.

Ground-Dwelling Arthropod Communities of a Sky Island Mountain Range in Southeastern Arizona, USA: Obtaining a Baseline for Assessing the Effects of Climate Change.

The few studies that have addressed past effects of climate change on species distributions have mostly focused on plants due to the rarity of historical faunal baselines. However, hyperdiverse groups like Arthropoda are vital to monitor in order to understand climate change impacts on biodiversity. This is the first investigation of ground-dwelling arthropod (GDA) assemblages along the full elevation gradient of a mountain range in the Madrean Sky Island Region, establishing a baseline for monitoring future changes in GDA biodiversity. To determine how GDA assemblages relate to elevation, season, abiotic variables, and corresponding biomes, GDA were collected for two weeks in both spring (May) and summer (September) 2011 in the Santa Catalina Mountains, Arizona, using pitfall traps at 66 sites in six distinct upland (non-riparian/non-wet canyon) biomes. Four arthropod taxa: (1) beetles (Coleoptera), (2) spiders (Araneae), (3) grasshoppers and crickets (Orthoptera), and (4) millipedes and centipedes (Myriapoda) were assessed together and separately to determine if there are similar patterns across taxonomic groups. We collected 335 species of GDA: 192/3793 (species/specimens) Coleoptera, 102/1329 Araneae, 25/523 Orthoptera, and 16/697 Myriapoda. GDA assemblages differed among all biomes and between seasons. Fifty-three percent (178 species) and 76% (254 species) of all GDA species were found in only one biome and during only one season, respectively. While composition of arthropod assemblages is tied to biome and season, individual groups do not show fully concordant patterns. Seventeen percent of the GDA species occurred only in the two highest-elevation biomes (Pine and Mixed Conifer Forests). Because these high elevation biomes are most threatened by climate change and they harbor a large percentage of unique arthropod species (11-25% depending on taxon), significant loss in arthropod diversity is likely in the Santa Catalina Mountains and other isolated mountain ranges in the Southwestern US.

The use of paracetamol (acetaminophen) among a community sample of people with chronic non-cancer pain prescribed opioids.

BACKGROUND: The regular use of simple analgesics in addition to opioids such as paracetamol (or acetaminophen) is recommended for persistent pain to enhance analgesia. Few studies have examined the frequency and doses of paracetamol among people with chronic non-cancer pain including use above the recommended maximum daily dose. AIMS: To assess (i) the prevalence of paracetamol use among people with chronic non-cancer pain prescribed opioids, (ii) assess the prevalence of paracetamol use above the recommended maximum daily dose and (iii) assess correlates of people who used paracetamol above the recommended maximum daily dose including: age, gender, income, education, pain severity and interference, use of paracetamol/opioid combination analgesics, total opioid dose, depression, anxiety, pain self-efficacy or comorbid substance use, among people prescribed opioids for chronic non-cancer pain. METHODS: This study draws on baseline data collected for the Pain and Opioids IN Treatment (POINT) study and utilises data from 962 interviews and medication diaries. The POINT study is national prospective cohort of people with chronic non-cancer pain prescribed opioids. Participants were recruited from randomly selected pharmacies across Australia. RESULTS: Sixty-three per cent of the participants had used paracetamol in the past week (95% CI = 59.7-65.8). Among the paracetamol users 22% (95% CI = 19.3-24.6) had used paracetamol/opioid combination analgesics and 4.8% (95% CI = 3.6-6.3) had used paracetamol above the recommended maximum daily dose (i.e. > 4000 mg/day). Following binomial logistic regression (χ(2) = 25.98, df = 10, p = 0.004), people who had taken above the recommended maximum daily dose were less likely to have low income (AOR = 0.52, 95% CI = 0.27-0.99), more likely to use paracetamol/opioid combination analgesics (AOR = 2.01, 95% CI = 1.02-3.98) and more likely to take a higher opioid dose (AOR = 1.00, 95% CI = 1.00-1.01). CONCLUSION: The majority of people with chronic non-cancer pain prescribed opioids report using paracetamol appropriately. High income, use of paracetamol/opioid combination analgesics and higher opioid dose were independently associated with paracetamol use above the recommended maximum daily dose.