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Abstract Background The objective of this research was the development and evaluation of 203Pb-labelled panitumumab (203Pb-PSC-panitumumab) as an immuno-SPECT radioligand for the detection of EGFR + head and neck squamous cell carcinoma (HNSCC) in a patient-derived xenograft (PDX) mouse model. The 51.9 h physical half-life and favourable γ-emission (279 keV; 81%) of 203Pb offer an excellent opportunity for developing immuno-SPECT radioligands. Moreover, 203Pb has a complementary therapeutic radionuclide (212Pb), making 203Pb and 212Pb an ideal matched radiotheranostic pair. Results Radiolabeling of panitumumab was performed at a pH of 5.0 and room temperature for 5–10 min with [203Pb]Pb(OAc)2, and the incorporation efficiency was determined using radio-TLC. 203Pb-PSC-panitumumab (~ 10 MBq, 140 μl of saline) was injected into the tail vein of NRG mice bearing subcutaneous (s.c.) HNSCC patient-derived xenografts (PDX). SPECT/CT images were acquired at 48 and 120 h post-injection. For biodistribution studies, mice were euthanized five days after 203Pb-panitumumab injection. The tumour and normal tissues were collected and weighed, and uptake of 203Pb was measured in a γ-counter. The uptake was calculated as the percent injected dose per gram of each tissue (ID%/g). Blocking experiments were performed by pretreating a group of mice (n = 5) with 1 mg of panitumumab 1 h before administering 203Pb-PSC-panitumumab. 4–5 chelators of a new lead-specific chelator (PSC) were attached per antibody; radiolabeling efficiency was 99.2 ± 0.7%. The isolated radiochemical yield of 203Pb-PSC-panitumumab was 41.4 ± 8% (n = 5), and the molar activity was 1.2 ± 0.35 GB/mg. SPECT imaging and biodistribution confirmed high accumulation and retention of 203Pb-PSC-panitumumab in the tumour (26% ID/g) at 120 h post-injection (p.i.), which could be reduced to 6.2%ID/g at 120 h p.i. by predosing with panitumumab (1 mg) confirming EGFR specificity of 203Pb-PSC-panitumumab uptake. Conclusions Panitumumab was successfully and reproducibly labelled with 203Pb in high radiochemical purity using the chelator PSC-NCS. 203Pb-PSC-panitumumab was specifically accumulated and retained in EGFR + tumours in NRG mice with s.c. HNSCC PDX. 203Pb-PSC-panitumumab is a suitable immuno-SPECT radioligand for imaging EGFR + tumours and has great potential for combining with 212Pb-PSC-panitumumab in a radiotheranostic strategy for imaging and treating HNSCC.

Mammalian DNA extracted from the invertebrates, especially blowfly-derived DNA, has been suggested as a useful tool to complement traditional field methods for terrestrial mammal monitoring. However, the accuracy of the estimated location of the target mammal detected from blowfly-derived DNA is largely dependent on the knowledge of blowflies' dispersal range. Presently, published data on adult blowfly dispersal capabilities remain scarce and mostly limited to temperate and subtropical regions, with no published report on the adult blowfly dispersal range in the Tropics. We seek to determine the blowfly flight range and dispersal activity in a tropical plantation in Malaysia by mark-release-recapture of approximately 3000 wild blowflies by use of rotten fish-baited traps for nine consecutive days. Out of the 3000 marked Chrysomya spp., only 1.5% (43) were recaptured during the 9-day sampling period. The majority of the blowflies (79%) were recaptured 1 km from the release point, while 20.9% were caught about 2-3 km from the release point. One individual blowfly travelled as far as 3 km and before being recaptured, which was the maximum dispersal distance recorded in this study. This result suggests that the estimated locations of the mammals detected from blowfly-derived iDNA is likely to be within 1-2 km radius from the origin of the blowfly sampling location. However, a more accurate estimated distance between the target mammal and the blowfly sampling location requires further investigation due to various factors, such as blowfly species, wind speed and direction that may potentially affect the blowfly dispersal activities. This study contributes further understanding on the development of a blowfly-derived DNA method as a mammalian monitoring tool in the tropical forests.

Social and environmental determinants of health (SEDoH) are crucial for achieving a holistic understanding of patient health. In fact, geographic factors may have more influence on health outcomes than patients’ genetics. Integrating SEDoH into the electronic health record (EHR), however, poses notable technical and compliance-related challenges. We evaluated barriers to the integration of SEDoH in the EHR and developed a privacy-preserving strategy to mitigate risk of protected health information exposure. Using coded identifiers for patient addresses, the strategy evaluates an alternative approach to ensure efficient, secure geocoding of data while preserving privacy throughout the data enrichment processes from numerous SEDoH data sources.

Abstract Background This study was conducted to determine whether heartworm infective larvae (L3) collected from mosquitoes fed on dogs during low-dose, short-treatment-regimen doxycycline and ivermectin could develop normally in dogs. Methods Twelve Beagles in a separate study were infected with 10 pairs of adult male and female Dirofilaria immitis by IV transplantation and randomly allocated to three groups of four dogs. Starting on Day 0, Group 1 received doxycycline orally at 10 mg/kg sid for 30 days plus ivermectin (min., 6 mcg/kg) on Days 0 and 30; Group 2 received doxycycline orally at 10 mg/kg sid until individual dogs became microfilaria negative (72–98 doses) and ivermectin every other week for six to seven doses. These dogs served as microfilaremic blood donors for the current mosquito studies. Aedes aegypti were allowed to feed on group-pooled blood samples from treated Groups 1-M and 2-M and untreated control Group 3-M on Days 22 (Study M-A) and 42 (Study M-C) and from Groups 1-M and 2-M on Day 29 (Study M-B) after treatment was started. From the Day 22 mosquito feeding, two dogs in Groups 1-M and 2-M and one dog in Group 3-M were given 50 L3 by SC inoculation. From the Day 29 feeding, two dogs in Groups 1-M and 2-M were given 50 L3. From the Day 42 feeding, two dogs in Group 1-M received 30 L3, while two dogs in Group 2-M and one dog in Group 3-M received 40 L3. All 14 dogs were necropsied for recovery and enumeration of adult heartworms 163–183 days PI. Results None of the 12 dogs that received L3 from mosquitoes fed on blood from treated dogs 22, 29 or 42 days after treatment started had any adult heartworms at necropsy, while the two control dogs had a total of 26 and 43 heartworms, respectively. Conclusions Treatment of microfilaremic dogs with doxycycline plus an ML, which later renders the L3 incapable of normal development in the animal host, widens the scope of the multimodal approach to heartworm prevention in reducing the spread of heartworm disease. Graphical Abstract

Abstract Background Microfilarial (mf) counts were monitored over 21.3 months for any rebound that might occur in counts, and adulticidal efficacy was assessed following administration of low dosage with short- and long-treatment regimens of doxycycline and ivermectin to heartworm-microfilaremic dogs. Methods Twelve heartworm-naïve beagles infected with 10 pairs of adult Dirofilaria immitis by intravenous transplantation were randomly allocated to three groups of four dogs. All treatments started on day 0. On day 0, Group 1 (short-treatment regimen) received doxycycline orally at 10 mg/kg once daily for 30 days plus ivermectin orally (minimum, 6 mcg/kg) on days 0 and 30. Group 2 (long-treatment regimen) received doxycycline orally at 10 mg/kg once daily until individual dogs became mf-negative (72–98 days) and ivermectin every other week until individual dogs became mf-negative (6–7 doses). Group 3 was the untreated control. Mf counts and antigen (Ag) tests were conducted. Dogs were necropsied for recovery and enumeration of heartworms on day 647. Results Day −1 mean mf counts were 15,613, 23,950, and 15,513 mf/ml for groups 1, 2, and 3, respectively. Mean counts for Groups 1 and 2 declined until days 239 and 97, respectively, when all were negative. Group 3 had high mf counts throughout the study. There was not a rebound in mf counts in any of the treated dogs after they became amicrofilaremic. All dogs in group 1 and group 3 were Ag-positive throughout the study and had at least one live female worm at necropsy. All dogs in treated Group 2 were positive for Ag through day 154, but were antigen-negative on days 644 and 647, as all had only male worms. Mean live adult worm recoveries for Groups 1, 2, and 3 were 6.8 (range, 5–8), 3.3 (range, 1–6), and 16.0 (range, 14–17), respectively, with a percent reduction in adult worm counts of 57.5% for Group 1 and 79.3% for Group 2. Conclusions These data lend support to the use of the American Heartworm Society Canine Guidelines for adulticide therapy recommending the initiation of doxycycline plus a macrocyclic lactone (ML) at the time of the heartworm-positive diagnosis. Graphical Abstract

This paper discusses the derivation of a set of dynamic load factors for calculation of walking response on the basis of measurements made during a biomechanics research carried out with young adults. Firstly, a quite large number of experimental data on single footstep force were collected. The single footstep forces were then superimposed to generate the force time history for a continuous walk. This was followed by the transformation of the resultant force to the frequency domain from which the dynamic load factors for the first ten harmonics of a pacing rate can be extracted. A statistical analysis was employed on the dynamic load factors to acquire their design values in terms of the 90-th or 95-th percentile. The waking force function recommended by various design guides and that developed in the paper were then used in a comprehensive finite element model to predict the vibration level of a building floor. Current design guides on floor vibration normally suggest using four harmonics in the walking force whereas load factors for ten harmonics were developed in this paper. The acceleration response of the floor was found to increase by 5-33 % when walking harmonics beyond the fourth harmonic were considered. The inclusion of higher harmonics would therefore lead to a more conservative estimation of the floor response.

This article highlights recent developments of SPECT and PET diagnostic imaging surrogates for targeted alpha particle therapy (TAT) radiopharmaceuticals. It outlines the rationale for using imaging surrogates to improve diagnostic-scan accuracy and facilitate research, and the properties an imaging-surrogate candidate should possess. It evaluates the strengths and limitations of each potential imaging surrogate. Thirteen surrogates for TAT are explored: 133La, 132La, 134Ce/134La, and 226Ac for 225Ac TAT; 203Pb for 212Pb TAT; 131Ba for 223Ra and 224Ra TAT; 123I, 124I, 131I and 209At for 211At TAT; 134Ce/134La for 227Th TAT; and 155Tb and 152Tb for 149Tb TAT.

Abstract The aims of the current study, therefore, were to compare (1) free-living MPS and (2) muscle and metabolic adaptations to resistance exercise in South Asian and white European adults. Eighteen South Asian and 16 White European men were enrolled in the study. Free-living muscle protein synthesis was measured at baseline. Muscle strength, body composition, resting metabolic rate, VO2max and metabolic responses (insulin sensitivity) to a mixed meal were measured at baseline and following 12 weeks of resistance exercise training. Free-living muscle protein synthesis was not different between South Asians (1.48 ± 0.09%/day) and White Europeans (1.59 ± 0.15%/day) (p = 0.522). In response to resistance exercise training there were no differences, between South Asians and White Europeans, muscle mass, lower body strength or insulin sensitivity. However, there were differences between the ethnicities in response to resistance exercise training in body fat, resting carbohydrate and fat metabolism, blood pressure, VO2max and upper body strength with responses less favourable in South Asians. In this exploratory study there were no differences in muscle protein synthesis or anabolic and metabolic responses to resistance exercise, yet there were less favourable responses in several outcomes. These findings require further investigation.

Objective: To study the impact of a 60-day pilot of an innovative virtual-care model using general internal medicine physicians and nurses to respond rapidly to more than 1200 coronavirus disease-2019 (COVID-19)-positive nasopharyngeal polymerase chain reaction tests. Patients and Methods: The current study was approved by the Mayo Clinic COVID-19 Research Committee and the Mayo Clinic Institutional Review Board. The data for all SARS-CoV-2–positive patients treated by our team were entered into a prospectively maintained internal research electronic data capture database. We searched this database retrospectively for the first 60 days of our program (March 23, 2020 to May 22, 2020). The data included basic deidentified demographics; symptoms at intake into the program; date of symptom onset; risk factors; location; and outcomes including hospitalization, admission to intensive care unit, and death. Results: Patients were contacted, on average, 6.3 hours after their results became available. There was a total of 138 ED visits. Of these, 40% were admitted to the hospital, with 36% of those admitted requiring intensive care unit level of care. Of the 849 patients in this sample, there were only 2 deaths (0.23%) at 60 days. Conclusion: Our innovative multidisciplinary COVID team provided excellent clinical care for patients with COVID, with a very low mortality rate compared with the national average. Although data are not available on a national scale for time to contact patient, our team was able to contact patients within the established recommendation for contact within 48 hours of testing, which is optimal.

Abstract This study reports the high-yield production of a novel 133/135La theranostic pair at a 22 MeV proton beam energy as an attractive alternative to the recently introduced 132/135La pair, demonstrating over an order of magnitude production increase of 133/135La (231 ± 8 MBq 133La and 166 ± 5 MBq 135La at End of Bombardment (EOB)) compared to 11.9 MeV production of 132/135La (0.82 ± 0.06 MBq 132La and 19.0 ± 1.2 MBq 135La) for 500 µA·min irradiations. A new sealed solid cyclotron target is introduced, which is fast to assemble, easy to handle, storable, and contains reusable components. Radiolabeling with macrocyclic chelators DOTA and macropa achieved full incorporation, with respective apparent 133La molar activites of 33 ± 5 GBq/µmol and 30 ± 4 GBq/µmol. PET centers with access to a 22 MeV capable cyclotron could produce clinically-relevant doses of 133/135La, via natBa irradiation, as a standalone theranostic agent for PET imaging and Auger electron therapy. With lower positron energies and less energetic and abundant gamma rays than 68Ga, 44Sc and 132La, 133La appears to be an attractive radiometal candidate for PET applications requiring a higher scanning resolution, a relatively long isotopic half-life, ease of handling, and a low patient dose.

Abstract Background People with young-onset dementia (YOD) can often struggle getting the right treatment. This is because of their frequently different characteristics and needs compared to people with late-onset dementia. The aim of this project was to assess a memory service for its adaptation to the needs and wishes of people with YOD and their carers. Methods This project evaluated a memory service in the North West of England by performing two focus groups with clinical staff and six semi-structured interviews with people with YOD and carers. The focus groups took place on site and lasted one hour each. People with YOD and their carers were identified via the memory clinics caseload and via the local Alzheimer’s Society charity organisation. Both focus groups and interviews were audio-recorded and transcribed, and data were analysed using thematic analysis. The public (a person living with YOD and his carer) were involved from the design stages of the project through to the analysis and dissemination. Results Eleven members of staff with different clinical backgrounds participated in the focus groups and six interviews were held with people with YOD and their carers. Both indicated that whilst the diagnostic process is relatively well conducted at the service, the post-diagnostic service has many gaps. These include limited post-diagnostic support by the service, better enabling peer support, as well as providing meaningful activities, as some activities provided might be more suitable to older adults with dementia. Conclusions Post-diagnostic services and support for people with YOD and their carers need to be improved. The next step will be to implement the findings from this service evaluation in practice and improve service satisfaction and relevance to people with YOD.

Flare frequency distributions represent a key approach to addressing one of the largest problems in solar and stellar physics: determining the mechanism that counterintuitively heats coronae to temperatures that are orders of magnitude hotter than the corresponding photospheres. It is widely accepted that the magnetic field is responsible for the heating, but there are two competing mechanisms that could explain it: nanoflares or Alfvén waves. To date, neither can be directly observed. Nanoflares are, by definition, extremely small, but their aggregate energy release could represent a substantial heating mechanism, presuming they are sufficiently abundant. One way to test this presumption is via the flare frequency distribution, which describes how often flares of various energies occur. If the slope of the power law fitting the flare frequency distribution is above a critical threshold, α = 2 as established in prior literature, then there should be a sufficient abundance of nanoflares to explain coronal heating. We performed >600 case studies of solar flares, made possible by an unprecedented number of data analysts via three semesters of an undergraduate physics laboratory course. This allowed us to include two crucial, but nontrivial, analysis methods: preflare baseline subtraction and computation of the flare energy, which requires determining flare start and stop times. We aggregated the results of these analyses into a statistical study to determine that α = 1.63 ± 0.03. This is below the critical threshold, suggesting that Alfvén waves are an important driver of coronal heating.

The eighteenth data release (DR18) of the Sloan Digital Sky Survey (SDSS) is the first one for SDSS-V, the fifth generation of the survey. SDSS-V comprises three primary scientific programs or “Mappers”: the Milky Way Mapper (MWM), the Black Hole Mapper (BHM), and the Local Volume Mapper. This data release contains extensive targeting information for the two multiobject spectroscopy programs (MWM and BHM), including input catalogs and selection functions for their numerous scientific objectives. We describe the production of the targeting databases and their calibration and scientifically focused components. DR18 also includes ∼25,000 new SDSS spectra and supplemental information for X-ray sources identified by eROSITA in its eFEDS field. We present updates to some of the SDSS software pipelines and preview changes anticipated for DR19. We also describe three value-added catalogs (VACs) based on SDSS-IV data that have been published since DR17, and one VAC based on the SDSS-V data in the eFEDS field.

Background: The advent of cystic fibrosis transmembrane conductance regulator protein (CFTR) modulators like ivacaftor have revolutionised the treatment of cystic fibrosis (CF). However, due to the plethora of variances in disease manifestations in CF, there are inherent challenges in unified responses under CFTR modulator treatment arising from variability in patient outcomes. The pharmacokinetic (PK) data available for ivacaftor-lumacaftor cystic fibrosis (CF) transmembrane conductance regulator (CFTR) modulator drug combination is limited.Methods: Secondary objectives were to identify (1) patient characteristics and (2) the interactions between ivacaftor-lumacaftor responsible for interindividual variability (IIV).Results: Peak plasma concentrations (Cmax) of ivacaftor - lumacaftor were >10 fold lower than expected compared to label information. The one-way ANOVA indicated that the patient site had an effect on Cmax values of ivacaftor metabolites ivacaftor-M1, ivacaftor-M6, and lumacaftor (p < 0.001, p < 0.001, and p < 0.001, respectively). The Spearman’s rho test indicated that patient weight and age have an effect on the Cmax of lumacaftor (p = 0.003 and p < 0.001, respectively) and ivacaftor metabolite M1 (p = 0.020 and p < 0.001, respectively). Age (p < 0.001) was found to effect on Cmax of ivacaftor M6 and on Tmax of ivacaftor M1 (p = 0.026). A large impact of patient characteristics on the IIV of PK parameters Cmax and Tmax, was observed among the CF patients.Conclusion: Understanding the many sources of variability can help reduce this individual patient variability and ensure consistent patient outcomes.

This article describes the formation of The Tasmanian Historical Dataset a longitudinal data resource spanning the 19th and early 20th century. This resource contains over 1.6 million records drawn from digitised prison and hospital admission registers, military enlistment papers, births, deaths and marriages, census and muster records, arrival and departure lists, bank accounts and property valuations, maps and plans and meteorological observations. As well as providing an account of the many different sources that have been digitised coded and linked as part of this initiative, the article outlines current and past research uses to which this data has been put. Further information on tables and key variables is provided in an appendix.

La enfermedad fungosa más limitante del duraznero (Prunus pérsica, L. Batsch) en Colombia es la pudrición parda, Monilia spp., que afecta flores, brotes y frutos, causando pérdidas hasta del 80%. El objetivo de la investigación fue identificar el patógeno asociado a pudrición parda en cuatro variedades: Dorado, Rubidoux, Diamante y Rey negro en el departamento de Boyacá. El estudio inicio con la colecta de frutos enfermos en Jenesano, Paipa, Tuta, Sotaquirá y Nuevo Colón. En laboratorio se realizó la obtención, aislamiento y purificación de los hongos presentes. Se realizó también caracterización morfológica de las colonias y conidias sobre cultivos monospóricos y caracterización molecular mediante amplificación por PCR del ADN ribosomal empleando iniciadores ITS4 e ITS5. Se obtuvieron 32 aislamientos del género Monilia y se identificaron tres especies presentes en la zona muestreada: Monilia fructícola, Monilia fructígena y Monilia laxa, en 62,5%, 25% y 12,5%, respectivamente. En la amplificación de la región ribosomal se observaron diferencias entre las dos primeras especies, en el tamaño de las bases amplificadas, siendo M. fructicola de 550 pb y M. fructigena de 545pb. Este trabajo contribuye a la caracterización de las especies de Monilia que afectan al duraznero en varias regiones del departamento de Boyacá.

Abstract Conflicts between the interests of biodiversity conservation and other human activities pose a major threat to natural ecosystems and human well‐being, yet few methods exist to quantify their intensity and model their dynamics. We develop a categorization of conflict intensity based on the curve of conflict, a model originally used to track the escalation and deescalation of armed conflicts. Our categorization assigns six intensity levels reflecting the discourse and actions of stakeholders involved in a given conflict, from coexistence or collaboration to physical violence. Using a range of case studies, we demonstrate the value of our approach in quantifying conflict trends, estimating transition probabilities between conflict stages, and modeling conflict intensity as a function of relevant covariates. By taking an evidence‐based approach to quantifying stakeholder behavior, the proposed framework allows for a better understanding of the drivers of conservation conflict development across a diverse range of socioecological scenarios.

Category: Hindfoot; Trauma Introduction/Purpose: The lateral extensile approach (LEA) to the calcaneus has long been a popular surgical approach to treat calcaneal fractures. However, high rates of wound complications have led surgeons to investigate alternative approaches. As a result, the sinus tarsi approach has grown in popularity. The lateral extensile approach affords substantial visualization of the calcaneus. However, this visualization has never been compared in a quantitative manner to the sinus tarsi approach (STA). The objective of this cadaveric study is to compare calcaneal visualization afforded by a sinus tarsi approach and a lateral extensile approach. Methods: Seven pair-matched, fresh-frozen, below-knee cadaver specimens were obtained. For each pair, one side received an LEA and the other side received a STA. To identify areas of the calcaneus accessible by instrument, a curette was used to mark the visualized calcaneal surfaces. The calcaneus was then disarticulated and cleared of all soft tissue. The curette markings were then identified and marked with blue surgical marker. Photos were taken of each calcaneus, and visualized surface areas were calculated using Image J software. Results: There were no statistically significant differences in the articular surfaces accessible between the two approaches (831.99 mm2 for LEA vs. 903.41 mm2 for STA, p=0.53) including the anterior, middle, and posterior facets. The total calcaneal surface area accessible was 3107.08 mm2 for LEA and 1444.19 mm2 for STA (p=0.02). The LEA allowed better exposure to the lateral wall (p

Background: The U.S. Centers for Disease Control and Prevention (CDC) funds five Regional Tuberculosis Training and Medical Consultation Centers (RTMCCs) that provide training and consultation for tuberculosis (TB) control and management. RTMCC utilization for assistance with diagnosis and management of TB in children has not been described. We analyzed pediatric TB consultations performed across all RTMCCs in terms of question type, provider type, and setting. Methods: The CDC medical consultation database was queried for consultations regarding patients ≤ 18 years provided between 1/1/13–4/22/15 by all RTMCCs (Curry International TB Center, Heartland National TB Center, Mayo Clinic Center for TB, New Jersey Medical School Global TB Institute, Southeastern National TB Center). Each query was categorized into multiple subject areas based on provider type, setting, consultation topic, and patient age. Results: The 5 RTMCCs received 1164 pediatric consultation requests, representing approximately 20% of all consultations performed by the centers during the study period. Providers requesting consults were primarily physicians (46.3%) or nurses (45.0%). The majority of pediatric consult requests were from state and local public health departments (679, 58.3%) followed by hospital providers (199, 17.1%); fewer requests came from clinicians in private practice (84, 7.2%) or academic institutions (40, 3.4%). Consults addressed 14 different topics, most commonly management of children with TB disease (19.1%), latent TB infection (LTBI) (18.2%), diagnosis or laboratory testing (18.7%), and pharmacology (9.2%). Discussion: Pediatric consultations accounted for approximately 20% of all consultations performed by RTMCCs during the study period. RTMCCs were utilized primarily by public health departments regarding management of TB disease, LTBI, and diagnosis or laboratory testing. The relative underutilization of the RTMCCs by clinicians in non-public health settings, who often manage children with TB exposure or infection, warrants further study. As US TB case rates decline and providers become less experienced with childhood TB, medical consultation support may become increasingly important. Keywords: Tuberculosis, Pediatric, Consultation

Background: Mycobacterium abscessus complex (MAbsC) is a significant management dilemma when taking care of patients with cystic fibrosis (CF). Methods: We undertook a retrospective cohort analysis of all CF patients in whom MAbsC was isolated from 2005 to 2014. The natural history of MAbsC was determined and clinical factors examined in an attempt to predict transient compared to persistent colonization. Results: No correlation was found between recurrent MAbsC isolation and clinical factors such as body mass index, respiratory function, or age. Over two-thirds of our cohort cleared MAbsC colonization with no intervention and no consistent effect on lung function was identified. Four CF patients were initiated on treatment with only one successful outcome. Conclusion: This analysis demonstrates there are no clear predictors of those CF patients who will become persistently colonized with MAbsC and that a significant proportion will spontaneously clear carriage. As treatment success rate is poor, more work is urgently required in improving patient outcomes.

Introduced species lists provide essential background information for biological invasions research and management. The compilation of these lists is, however, prone to a variety of errors. We highlight the frequency and consequences of such errors using introduced Melaleuca (sensu lato, including Callistemon) species in South Africa as a case study. We examined 111 herbarium specimens from South Africa and noted the categories and sub-categories of errors that occurred in identification. We also used information from herbarium specimens and distribution data collected in the field to determine whether a species was introduced, naturalized and invasive. We found that 72% of the specimens were not named correctly. These were due to human error (70%) (misidentification, and improved identifications) and species identification problems (30%) (synonyms arising from inclusion of Callistemon, and unresolved taxonomy). At least 36 Melaleuca species have been introduced to South Africa, and field observations indicate that ten of these have naturalized, including five that are invasive. While most of the errors likely have negligible impact on management, we highlight one case where incorrect identification lead to an inappropriate management approach and some instances of errors in published lists. Invasive species lists need to be carefully reviewed to minimise errors, and herbarium specimens supported by DNA identification are required where identification using morphological features is particularly challenging.

Background Acute neurological events may present as an extrapulmonary complication in patients with cystic fibrosis (CF). These events can be secondary to a range of different aetiologies.Methods A retrospective analysis of 476 medical records of CF patients attending a large teaching hospital between 2000 and 2018 was performed. Patients presenting with acute neurological events who had MRI brain imaging were evaluated. Patients who had headaches without associated neurological symptoms were excluded from this analysis.Results Acute neurological presentations, excluding headaches without associated neurological symptoms, were reported in 27 index patients out of the 476 patients. Of these, 16 patients had MRI brain imaging for review. Three patients suffered pathology secondary to vascular events, both ischaemic and haemorrhagic; four patients had evidence of ischaemia or infarction not consistent with a vascular territory stroke and the remaining patients experienced a range of different neurological events. The most common presentation among these patients was seizure activity, followed by a transient motor or sensory deficit.Conclusions Neurological complications are recognised among individuals with CF. Although rare, they can be secondary to a range of different aetiologies, including dysfunctional cell energetics. Additional studies are required to further evaluate this association.

La fotorreportería del conflicto armado en Colombia entre 2002-2006 constituye una investigación concomitante al desarrollo de un proyecto de tesis doctoral. Este artículo se circunscribe a la metodología de esa primera investigación preliminar en cuanto base de una fuente primaria y estudio de esa fotorreportería del rotativo El Tiempo de Bogotá. De ahí que el volumen de ese archivo constituya hoy un repositorio visual del conflicto armado en Colombia de estimado valor para el Centro de Documentación en Imagen y Diseño de la Universidad de Caldas, Manizales, Colombia.

El tomate Solanum lycopersicum L es una hortaliza de gran importancia en el ámbito nacional. Dentro de las principales limitantes de este cultivo se encuentra la mosca blanca, Trialeurodes vaporariorum Westwood (Hemíptera: Aleyrodidae). Este estudio evaluó en laboratorio la capacidad reguladora de Chrysoperla externa Hagen(Neuroptera: Chrysopidae) sobre mosca blanca T. vaporariorum. A partir de plantas infestadas con T. vaporariorum, se tomaron foliolos con presencia de ninfas de la plaga y se depositaron en recipientes plásticos con tapa, adicionando un individuo en cada estado larval del depredador C. externa. Se emplearon densidades de presa de 50, 75 y 100 individuos en los dos instares iniciales del depredador y 100, 150 y 200 para el tercer instar, con un testigo con 50 individuos sin depredador. Se empleó un diseño completamente al azar en condiciones de laboratorio de 17,8 °C y 67,5% de humedad relativa. Se observaron diferencias estadísticas significativas entre densidades de presa en los tres instares evaluados. Se encontró, para cada una de las densidades de presas de T. vaporariorum evaluadas en primer instar de C. externa, porcentajes de mortalidad de 96,8%, 80,5% y 56,4%, respectivamente; para el segundo instar, mortalidades de 94,4%, 77,5% y 75,4%, en su orden y para el tercer instar mortalidades de 99,1 %, 90% y 76,6%, respectivamente. De acuerdo con los resultados obtenidos, C. externa ejerce un efecto regulatorio, presentando una respuesta funcional tipo II en sus tres instares larvales, cuando actúa como depredador de ninfas de T. vaporariorum.

Trialeurodes vaporariorum Westwood (Hemíptera: Aleyrodidae) es uno de los principales limitantes del cultivo de tomate Solanum lycopersicum, por generar problemas directos e indirectos en este sistema de producción; para el manejo de este insecto (mosca blanca) se acude a excesivas aplicaciones de productos de síntesis química, sin obtener los mejores resultados. Este estudio consistió en evaluar, en condiciones de invernadero, la capacidad reguladora de Chrysoperla externa Hagen (Neuróptera: Chrysopidae) sobre la mosca blanca presente en tomate. En plantas infestadas con individuos de T. vaporariorum se adicionó C. externa en niveles poblacionales de 80, 160 y 240 individuos en estado larval por planta, y se contó con un testigo sin depredador. Se empleó un diseño completamente al azar en condiciones de invernadero (temperatura promedio de 20 ºC y humedad relativa del 60 %). Se observaron diferencias estadísticamente significativas entre las densidades del depredador, con infestaciones de 35, 52 y 53 % de T. vaporariorum (tras cuatro semanas), correspondientes a las liberaciones de 240, 160 y 80 individuos por planta, respectivamente. Se observó que las plantas del testigo presentaron menor altura y número de ramas, respecto de los tratamientos en los cuales había presencia del depredador C. externa.

El gusano blanco (Premnotrypes vorax Hustache) ocasiona pérdidas considerables en el cultivo de la papa, las cuales pueden llegar hasta el 100% dependiendo del nivel de infestación y manejo del cultivo. El objetivo del presente estudio fue determinar el efecto individual y combinado de dos aislamientos autóctonos de Beauveria spp. en comparación con dos bioplaguicidas a base de Metarhizium anisopliae y Beauveria brongniartii, sobre P. vorax en condiciones de campo. Se empleó el Diseño Completamente al Azar, con ocho tratamientos y cuatro repeticiones Se hicieron inoculaciónes mediante aspersión dirigida a la base de la planta, utilizando una concentración 5x108 conidias.g-1. Se evaluó porcentaje de daño, porcentaje de control y rendimiento al momento de cosecha (t ha-1). Los resultados indicaron que las cepas comerciales en combinación Metaril® W.P + B. brongniartii® W.P (T6) y el aislamiento autóctono de Beauveria sp. Bv01 (T1), presentaron los menores porcentajes de daño (3,1±0,06 y 3,5±0,2%), los mayores porcentajes de control (77±0,46 y 76,7±1,78%), y la mejor producción (19±0,40t ha-1 y 18±0,25t ha-1) con diferencias significativas (Duncan p≤0,05) respecto a los demás tratamientos y el control regional. Se destacó el T6, ya que mostró el mejor potencial biológico por su rendimiento en cosecha, representando una alternativa promisoria para el control de P. vorax al ser incorporado dentro de un esquema de manejo integrado de la plaga en la región.

Understanding the metabolic processes in energy metabolism, particularly during fasted exercise, is a growing area of research. Previous work has focused on measuring metabolites pre and post exercise. This can provide information about the final state of energy metabolism in the participants, but it does not show how these processes vary during the exercise and any subsequent post-exercise period. To address this, the work described here took fasted participants and subjected them to an exercise and rest protocol under laboratory settings, which allowed for breath and blood sampling both pre, during and post exercise. Analysis of the data produced from both the physiological measurements and the untargeted metabolomics measurements showed clear switching between glycolytic and ketolytic metabolism, with the liquid chromatography-mass spectrometry (LC-MS) data showing the separate stages of ketolytic metabolism, notably the transport, release and breakdown of long chain fatty acids. Several signals, putatively identified as short peptides, were observed to change in a pattern similar to that of the ketolytic metabolites. This work highlights the power of untargeted metabolomic methods as an investigative tool for exercise science, both to follow known processes in a more complete way and discover possible novel biomarkers.

Introduction. The diagnostic standard for Pneumocystis jirovecii pneumonia (PCP) is direct microscopic identification; however, in recent years, polymerase chain reaction (PCR) from bronchoalveolar lavage (BAL) samples to detect Pneumocystis nucleic acids has proven to be more sensitive and specific. Sputum samples have been presumed inferior to bronchoscopic samples secondary to variability and adequacy of sample collection. We observed several cases of positive sputum PCP-PCR results with negative PCP-PCR BAL results. The aim of the current study was to further characterize the clinical setting and outcomes in patients with positive sputum PCP-PCR samples and negative BAL PCP-PCR samples. Methods. We identified all patients who underwent P. jirovecii-PCR testing at Mayo Clinic between 2011 and 2016. Patients with a positive sputum and negative BAL sample collected within a 14-day time frame were identified and underwent further chart review for demographics, immunocompromised state, and clinical outcome. Results. From 2011 to 2016, 4431 respiratory samples from 3021 unique patients were tested for the presence of P. jirovecii by PCR. Fifty-five samples (1.2% of all samples collected) belonging to 24 unique patients (0.79% of patients tested) were identified as having a positive and negative sample collected within 14 days. Of these 24 patients, 10 (46%) patients had a positive sputum or tracheal secretion sample with negative BAL or bronchial washings. Out of these 10 patients, 8 were immunocompromised and 9 underwent treatment for PCP with 6 patients improving. Conclusion. Our results suggest that discordant P. jirovecii-PCR testing results from sputum and bronchoscopic specimens are an infrequent occurrence. Patients with positive P. jirovecii-PCR sputum/tracheal secretion samples and negative bronchoscopic samples appear to be clinically infected and respond to PCP treatment. Sputum P. jirovecii-PCR testing may be a viable alternative to invasive testing.

En Colombia las pérdidas ocasionadas por Moniliophthora roreri Cif & Par en el cultivo de cacao, son considerables y los métodos de control tradicional no son suficientes. Para el manejo de la enfermedad el control biológico, surge como alternativa económicamente viable y ambientalmente sostenible. El objetivo del presente estudio fue evaluar el control de Moniliophthora roreri mediante parámetros de incidencia y severidad, utilizando aislamientos nativos y cepas comerciales de Trichoderma spp., en combinación con prácticas culturales (PC). Se evaluaron diez tratamientos, los cuales resultaron de combinar prácticas culturales, productos biológicos comerciales, aislamientos nativos de hongos y funguicidas de síntesis química. Para la evaluación, se empleó un diseño completamente aleatorio (DCA) con cuatro repeticiones, para un total de 40 UE cada una compuesta por una planta del clon TCS01 (Theobroma CORPOICA la Suiza 01). Se hizo inoculación dirigida al dosel, utilizando una concentración de 1,2, 1,5 y 2,9 x107 UFC.g-1 para aislamientos nativos y 2,0 y 5,0 x108 UFC.g-1 para cepas comerciales. Se evaluó incidencia y severidad externa en los frutos durante 25 semanas. Los resultados indicaron que los frutos inoculados con el tratamiento T7 (P.C + Safer soil ®W.P) y T4 (P.C + mezcla Trichoderma H20, H3, H5), presentaron los menores porcentajes de incidencia y severidad externa y los mayores rendimientos de cosecha sin diferencias significativas respecto al control químico y regional, representando una alternativa promisoria para la producción de cacao en la subregión occidental de Boyacá.

The speckle-type POZ protein (SPOP) is a tumor suppressor in prostate cancer (PCa). SPOP somatic mutations have been reported in up to 15% of PCa of those of European descent. However, the genetic roles of SPOP in African American (AA)-PCa are currently unknown. We sequenced the SPOP gene to identify somatic mutations in 49 AA prostate tumors and identified three missense mutations (p.Y87C, p.F102S, and p.G111E) in five AA prostate tumors (10%) and one synonymous variant (p.I106I) in one tumor. Intriguingly, all of mutations and variants clustered in exon six, and all of the mutations altered conserved amino acids. Moreover, two mutations (p.F102S and p.G111E) have only been identified in AA-PCa to date. Quantitative real-time polymerase chain reaction analysis showed a lower level of SPOP expression in tumors carrying SPOP mutations than their matched normal prostate tissues. In addition, SPOP mutations and novel variants were detected in 5 of 27 aggressive PCa and one of 22 less aggressive PCa (P < 0.05). Further studies with increased sample size are needed to validate the clinicopathological significance of these SPOP mutations in AA-PCa.

Se evaluó la eficacia de hongos entomopatógenos nativos en el biocontrol de Tecia solanivora (Lepidoptera: Gelechiidae) in vitro. Los aislamientos fueron obtenidos de larvas y adultos de gusano blanco Premmotrypes vorax, barrenador del curubo Aepytus sp, picudo de la palma Rinchophorus palmarum, broca del café Hypothenemus hampei, polilla guatemalteca Tecia solanivora y palomilla de la papa Phthorimaea operculella infectados, de los municipios de Ventaquemada, Umbita, Coper (Boyacá) y San gil (Santander). El trabajo se realizó en el laboratorio de control biológico del Grupo Manejo Biológico de Cultivos en Tunja, Colombia. Se seleccionaron in vitro, de forma preliminar cinco de los siete aislamientos de hongos obtenidos: Bv01, Bv03, Bv04, Bv05 y Bv07, los cuales ocasionaron mortalidades superiores al 10%. De acuerdo con la caracterización morfológica realizada, los hongos encontrados pertenecen al género Beauveria. La evaluación de su eficacia se realizó con 10 larvas de T. solanivora desinfectadas y sumergidas en suspensión de 1x107esporas.mL-1, las cuales se observaron durante 32 días, registrando cada 8 días la mortalidad. Se empleó un diseño completamente al azar, con 6 tratamientos, 4 repeticiones y una prueba de separación de medias de Tukey. Los resultados mostraron que 32 días después de la inoculación los aislamientos Bv03 y Bv05 fueron los que produjeron la mayor mortalidad acumulada (7,4 y 8,5%, respectivamente). Se confirma el bajo potencial de los hongos entomopatógenos nativos para el control de larvas de T. solanivora.

Las “cochinillas de humedad” (Crustacea: isopoda), han ido surgiendo como organismos plaga de importancia en agricultura, en países como Brasil y Argentina, en donde causan daños en soya, girasol y pastos. Recientemente se han detectado en Boyacá, afectando cebolla de bulbo, frijol y frutales. Por lo anterior, fué necesario iniciar la caracterización de las especies presentes y la determinación de su impacto en la producción hortícola en algunos municipios de esta región. Se realizó muestreos en Paipa, Tibasosa, Nobsa y Santa Rosa de Viterbo, para determinar la presencia y diversidad de especies de “cochinilla de humedad”; así como, una encuesta para establecer la percepción que tenían los agricultores del daño de estos crustáceos y las estrategias de manejo empleadas. Se evaluaron 8 veredas en Paipa, 7 en Nobsa, 3 en Tibasosa y 1 en Santa Rosa de Viterbo. Se comprobó la presencia de “cochinillas de humedad” en cultivos de frutales, hortalizas y otros, en los municipios muestreados. Se identificaron las especies: Porcellios caber, Porcellio dilatatus, Porcellio pruinosus, Armadillidium vulgare y Armadillidium nasatum. El daño por estos organismos se evidenció en lechuga, brócoli, repollo, remolacha, espinaca, cebolla, cilantro, durazno, frijol, fresa, maíz y papa, especialmente en semillero. El daño observado fué mordedura en hojas (50%), raíz (32,35%), tallo (20,85%) y ramas (2,94%). Se percibió falta de conocimiento de los agricultores en el manejo de las “cochinillas de humedad”, utilizándose insecticidas en un 79,41% de los casos, un manejo orgánico en 2,99% y ningún manejo en el 5,88%.

Climate is frequently used to predict the outcome of species introductions based on the results from species distribution models (SDMs). However, despite the widespread use of SDMs for pre- and post-border risk assessments, data that can be used to validate predictions is often not available until after an invasion has occurred. Here we explore the potential for using historical forestry trials to assess the performance of climate-based SDMs. SDMs were parameterized based on the native range distribution of 36 Australian acacias, and predictions were compared against both the results of 150 years of government forestry trials, and current invasive distribution in southern Africa using true skill statistic, sensitivity and specificity. Classification tree analysis was used to evaluate why some Australian acacias failed in trials while others were successful. Predicted suitability was significantly related to the invaded range (sensitivity = 0.87) and success in forestry trials (sensitivity = 0.80), but forestry trial failures were under-predicted (specificity = 0.35). Notably, for forestry trials, the success in trials was greater for species invasive somewhere in the world. SDM predictions also indicate a considerable invasion potential of eight species that are currently naturalized but not yet widespread. Forestry trial data clearly provides a useful additional source of data to validate and refine SDMs in the context of risk assessment. Our study identified the climatic factors required for successful invasion of acacias, and accentuates the importance of integration of status elsewhere for risk assessment.

This report on the Vespucci Institute on health geography in 2013 emphasizes the importance of research that connects population, health, and place from a holistic perspective. We review important trends related to Health GIS and highlight directions for future research in this area that were identified at the Institute.

Diabetes is a major health problem worldwide, and there is substantial interest in developing xenogeneic islet transplantation as a potential treatment. The potential to relieve the demand on an inadequate supply of human pancreata is dependent upon the efficiency of techniques for isolating and culturing islets from the source pancreata. Porcine islets are favored for xenotransplantation, but mature pigs (>2 years) present logistic and economic challenges, and young pigs (3–6 months) have not yet proven to be an adequate source. In this study, islets were isolated from 20 juvenile porcine pancreata (~3 months; 25 kg Yorkshire pigs) immediately following procurement or after 24 h of hypothermic machine perfusion (HMP) preservation. The resulting islet preparations were characterized using a battery of tests during culture in silicone rubber membrane flasks. Islet biology assessment included oxygen consumption, insulin secretion, histopathology, and in vivo function. Islet yields were highest from HMP-preserved pancreata (2,242 ± 449 IEQ/g). All preparations comprised a high proportion (>90%) of small islets (

Chronic pelvic pain (CPP) affects 5.7-26.6% women worldwide. 55% have no obvious pathology and 40% have associated endometriosis. Neuropathic pain (NeP) is pain arising as a consequence of a lesion/disease affecting the somatosensory system. The prevalence of NeP in women with CPP is not known. The diagnosis of NeP is challenging because there is no gold-standard assessment. Questionnaires have been used in the clinical setting to diagnose NeP in other chronic pain conditions and quantitative sensory testing (QST) has been used in a research setting to identify abnormal sensory function. We aimed to determine if women with chronic pelvic pain (CPP) have a neuropathic pain (NeP) component to their painful symptoms and how this is best assessed. We performed an exploratory prospective cohort study of 72 pre-menopausal women with a diagnosis of CPP. They underwent a clinician completed questionnaire (DN4) and completed the S-LANSS and PainDETECT™ questionnaires. Additionally QST testing was performed by a clinician. They also completed a patient acceptability questionnaire. Clinical features of NeP were identified by both questionnaires and QST. Of the women who were NeP positive, 56%, 35% and 26% were identified by the S-LANSS, DN4 and PainDETECT™ respectively. When NeP was identified by questionnaire, the associated laparoscopy findings were similar irrespective of which questionnaire was used. No subject had entirely unchanged QST parameters. There were distinct loss and gain subgroups, as well as mixed alteration in function, but this was not necessarily clinically significant in all patients. 80% of patients were confident that questionnaires could diagnose NeP, and 90% found them easy to complete. Early identification of NeP in women with CPP with a simple questionnaire could facilitate targeted therapy with neuromodulators, which are cheap, readily available, and have good safety profiles. This approach could prevent unnecessary or fertility-compromising surgery and prolonged treatment with hormones.

During extensive ongoing campaigns to inventory moths of North America and Area de Conservacion Guanacaste (ACG), northwestern Costa Rica, we discovered that morphologically similar yponomeutid moths were assigned two different names, Atteva ergatica Walsingham in Costa Rica and A. punctella (Stoll) in North America, but had identical DNA barcodes. Combining DNA barcoding, morphology and food plant records also revealed a complex of two sympatric species that are diagnosable by their DNA barcodes and their facies in Costa Rica. However, neither of the names could be correctly applied to either species, as A. ergatica is a junior synonym and A. punctella a junior homonym. By linking our specimens to type material through morphology and DNA barcoding, we determined that the ACG dry forest species, distributed from Costa Rica to southern Quebec and Ontario, should be called A. aurea, whereas the similar and marginally sympatric ACG rain forest species found in Central America should be called A. pustulella. Neotypes are designated for Phalaena Tinea punctella Stoll, 1781 and Deiopeia aurea Fitch, 1857. Atteva floridana has identical barcodes to A. aurea and provisionally maintained as a synonym.

Ceragenins were designed as non-peptide mimics of endogenous antimicrobial peptides, and they display broad-spectrum antibacterial and antifungal activities, including the ability to eradicate established biofilms. These features of ceragenins make them attractive potential therapeutics for persistent infections in the lung, including those associated with cystic fibrosis. A characteristic of an optimal therapeutic for use in the lungs and trachea is the exertion of potent antimicrobial activities without damaging the cilia that play a critical role in these tissues. In previous work, potent antimicrobial activities of ceragenin CSA-131 have been reported; however, we found in ex vivo studies that this ceragenin, at concentrations necessary to eradicate established biofilms, also causes loss of cilia function. By formulating CSA-131 in poloxamer micelles, cilia damage was eliminated and antimicrobial activity was unaffected. The ability of CSA-131, formulated with a poloxamer, to reduce the populations of fungal pathogens in tracheal and lung tissue was also observed in ex vivo studies. These findings suggest that CSA-131, formulated in micelles, may act as a potential therapeutic for polymicrobial and biofilm-related infections in the lung and trachea.

The Andean weevil Premnotrypes vorax represents an important cause of damage to Colombian potato crops. Due to the impact of this plague on the economy of the country, we searched for new alternatives for its biological control, based on the entomopathogenic bacteria Bacillus thuringiensis. A total of 300 B. thuringiensis strains obtained from potato plantations infested with P. vorax were analyzed through crystal morphology, SDS-PAGE, PCR and bioassays. We used site- directed mutagenesis to modify the Cry3Aa protein. Most of the B. thuringiensis isolates had a bipyramidal crystal morphology. SDS-PAGE analyses had seven strains groups with σ-endotoxins from 35 to 135 kDa. The genes cry 2 and cry 1 were significantly more frequent in the P. vorax habitat (PCR analyses). Three mutant toxins, 1 (D354E), 2 (R345A, ∆Y350, ∆Y351), and 3 (Q482A, S484A, R485A), were analyzed to assess their activity against P. vorax larvae. Toxicity was low, or absent, against P. vorax for isolates, wild type cry 3Aa and cry 3Aa mutants. The genetic characterization of the collection provides opportunities for the selection of strains to be tested in bioassays against other insect pests of agricultural importance, and for designing Cry proteins with improved insecticidal toxicity. Rev. Biol. Trop. 57 (4): 1235-1243. Epub 2009 December 01.El gorgojo andino Premnotrypes vorax es una causa importante de daño en los cultivos colombianos de este tubérculo. Debido al impacto que esta plaga tiene sobre la economía del país, nos interesamos en buscar alternativas nuevas para el control biológico de P. vorax, basadas en la bacteria entomopatógena Bacillus thuringiensis. Se recolectaron un total de 300 cepas de B. thuringiensis a partir de plantaciones de papa infestadas con P. vorax, las cuales fueron analizadas por medio de la morfología del cristal, SDS-PAGE, PCR y ensayos biológicos. La mayoría de los aislamientos de B. thuringiensis presentaron cristales bipiramidales. Los análisis de SDS-PAGE indicaron la presencia de siete grupos de cepas con σ- endotoxinas que variaban entre 35 a 135 kDa. Las pruebas con PCR demostraron que los genes cry 2 y cry 1 fueron significativamente más frecuentes en el medioambiente de P. vorax. Además, se utilizó la mutagénesis sitio-dirigida para modificar la proteína Cry3Aa. Se analizaron tres toxinas mutantes, 1 (D354E), 2 (R345A, ∆Y350, ∆Y351), y 3 (Q482A, S484A, R485A), para determinar su actividad contra larvas de P. vorax. Los ensayos de toxicidad señalaron escasa, o nula, actividad hacia P. vorax tanto para las cepas, la toxina Cry3Aa de referencia y las proteínas Cry3Aa mutantes. La caracterización genética de la colección puede proveer oportunidades para la selección de cepas que pueden evaluarse por medio de bioensayos contra otros insectos-plaga de importancia agrícola, y para el diseño de proteínas Cry con actividad toxica mejorada.

Ultrasound studies of carotid intima media thickness (cIMT) and plaques are limited in South Asians, a group at elevated cardiovascular disease (CVD) risk. We determined whether South Asians have a difference in these ultrasound markers compared to Europeans living in the United Kingdom and whether measured risk factor(s) could account for any such differences.One hundred South Asian men, aged 40 to 70 years and 100 European men of similar age and BMI, without diagnosed CVD or diabetes, underwent carotid ultrasound for measurement of cIMT and carotid plaque presence. Physical activity, cardiorespiratory fitness, anthropometry and blood pressure were assessed, fasted blood taken for measurement of cardiometabolic risk factors and demographic and lifestyle factors recorded.Age-adjusted mean (SD) cIMT was similar in South Asians and Europeans (0.64 (0.16) mm v 0.65 (0.12) mm, p = 0.64). Plaque was present in 48 South Asians and 37 Europeans and overall, there was no age-adjusted difference between South Asian and Europeans for plaque score(odds ratio 1.49, 95% CI, 0.86-2.80, p = 0.16), however, South Asians appeared to have more plaques at a younger age than Europeans; at age 40-50 years the odds of South Asians having plaques was 2.63 (95% CI, 1.16-5.93) times that for Europeans.cIMT is similar between healthy South Asian and European men. Whilst there was no overall difference in plaque presence in South Asians, there is an indication of greater plaque prevalence at younger ages--an observation requiring further investigation. Prospective studies linking plaques to CVD outcomes in South Asians are needed to investigate whether these measures help improve CVD risk prediction.

Light exposure can influence sleep and circadian timing, both of which have been shown to influence weight regulation. The goal of this study was to evaluate the relationship between ambient light, sleep and body mass index. Participants included 54 individuals (26 males, mean age 30.6, SD = 11.7 years). Light levels, sleep midpoint and duration were measured with wrist actigraphy (Actiwatch-L) for 7 days. BMI was derived from self-reported height and weight. Caloric intake was determined from 7 days of food logs. For each participant, light and activity data were output in 2 minute epochs, smoothed using a 5 point (10 minute) moving average and then aggregated over 24 hours. The mean light timing above 500 lux (MLiT500) was defined as the average clock time of all aggregated data points above 500 lux. MLiT500 was positively correlated with BMI (r = 0.51, p

Broader implementation of cell-based therapies has been hindered by the logistics associated with the expansion of clinically relevant cell numbers ex vivo. To overcome this limitation, Wilson Wolf Manufacturing developed the G-Rex, a cell culture flask with a gas-permeable membrane at the base that supports large media volumes without compromising gas exchange. Although this culture platform has recently gained traction with the scientific community due to its superior performance when compared with traditional culture systems, the limits of this technology have yet to be explored. In this study, we investigated multiple variables including optimal seeding density and media volume, as well as maximum cell output per unit of surface area. Additionally, we have identified a novel means of estimating culture growth kinetics. All of these parameters were subsequently integrated into a novel G-Rex “M” series, which can accommodate these optimal conditions. A multicenter study confirmed that this fully optimized cell culture system can reliably produce a 100-fold cell expansion in only 10 days using 1L of medium. The G-Rex M series is linearly scalable and adaptable as a closed system, allowing an easy translation of preclinical protocols into the good manufacturing practice.

Six hundred and eleven random-source dogs (338 male, 273 female) one year of age or older, from six sections of the city of Recife, Pernambuco, were examined antemortem for circulating microfilariae Dirofilaria immitis and Dipetalonema reconditum adult heartworm (D. immitis) antigen, and examined postmortem for adult heartworms. The prevalence of heartworm infection was 2.3% (14/611), as determined by necropsy for adult worms, and 1% (6/611) had circulating microfilariae of D. immitis; thus, 57.1% of the heartworm-infected dogs had occult infections. The results of serological testing indicated that 1.3% (8/611) of the dogs were positive for adult heartworm antigen. A total of 42 (6.9%) of the dogs had microfilariae of D. reconditum; 40 of these had only D. reconditum and two additional dogs had microfilariae of both species, D. immitis and D. reconditum.

The tolerable duration of continuous high-intensity exercise is determined by the hyperbolic Speed-tolerable duration (S-tLIM) relationship. However, application of the S-tLIM relationship to normalize the intensity of High-Intensity Interval Training (HIIT) has yet to be considered, with this the aim of present study. Subjects completed a ramp-incremental test, and series of 4 constant-speed tests to determine the S-tLIM relationship. A sub-group of subjects (n = 8) then repeated 4 min bouts of exercise at the speeds predicted to induce intolerance at 4 min (WR4), 6 min (WR6) and 8 min (WR8), interspersed with bouts of 4 min recovery, to the point of exercise intolerance (fixed WR HIIT) on different days, with the aim of establishing the work rate that could be sustained for 960 s (i.e. 4×4 min). A sub-group of subjects (n = 6) also completed 4 bouts of exercise interspersed with 4 min recovery, with each bout continued to the point of exercise intolerance (maximal HIIT) to determine the appropriate protocol for maximizing the amount of high-intensity work that can be completed during 4×4 min HIIT. For fixed WR HIIT tLIM of HIIT sessions was 399±81 s for WR4, 892±181 s for WR6 and 1517±346 s for WR8, with total exercise durations all significantly different from each other (P0.050). However, there was significantly less high-intensity work completed during bouts 2 (153.5±40. 9 m), 3 (136.9±38.9 m), and 4 (136.7±39.3 m), compared with bout 1 (264.9±58.7 m; P>0.050). These data establish that WR6 provides the appropriate work rate to normalize the intensity of HIIT between subjects. Maximal HIIT provides a protocol which allows the relative contribution of the work rate profile to physiological adaptations to be considered during alternative intensity-matched HIIT protocols.

Transplantation of photoreceptor precursor cells (PPCs) into the retina represents a promising treatment for cell replacement in blinding diseases characterized by photoreceptor loss. In preclinical studies, we and others demonstrated that grafted PPCs integrate into the host outer nuclear layer (ONL) and develop into mature photoreceptors. However, a key feature of light detecting photoreceptors, the outer segment (OS) with natively aligned disc membrane staples, has not been studied in detail following transplantation. Therefore, we used as donor cells PPCs isolated from neonatal double transgenic reporter mice in which OSs are selectively labeled by green fluorescent protein while cell bodies are highlighted by red fluorescent protein. PPCs were enriched using CD73-based magnetic associated cell sorting and subsequently transplanted into either adult wild-type or a model of autosomal-dominant retinal degeneration mice. Three weeks post-transplantation, donor photoreceptors were identified based on fluorescent-reporter expression and OS formation was monitored at light and electron microscopy levels. Donor cells that properly integrated into the host wild-type retina developed OSs with the formation of a connecting cilium and well-aligned disc membrane staples similar to the surrounding native cells of the host. Surprisingly, the majority of not-integrated PPCs that remained in the sub-retinal space also generated native-like OSs in wild-type mice and those affected by retinal degeneration. Moreover, they showed an improved photoreceptor maturation and OS formation by comparison to donor cells located on the vitreous side suggesting that environmental cues influence the PPC differentiation and maturation. We conclude that transplanted PPCs, whether integrated or not into the host ONL, are able to generate the cellular structure for effective light detection, a phenomenon observed in wild-type as well as in degenerated retinas. Given that patients suffering from retinitis pigmentosa lose almost all photoreceptors, our findings are of utmost importance for the development of cell-based therapies.