Unravelling heterogeneous malaria transmission dynamics in the Peruvian Amazon: insights from a cross-sectional survey.

BACKGROUND: Malaria remains a global health challenge, particularly in Peru's Loreto region. Despite ongoing efforts, high infection rates and asymptomatic cases perpetuate transmission. The Peruvian Ministry of Health's "Zero Malaria Plan" targets elimination. This novel study combines microscopic, molecular, and serological techniques to assess transmission intensity, identify epidemiological risk factors, and characterize species-specific patterns across villages. The findings aim to inform targeted interventions and support broader malaria elimination efforts in line with the Zero Malaria Plan initiative. METHODS: A cross-sectional malaria survey was conducted in the Zungarococha community, comprising the villages Llanchama (LL), Ninarumi (NI), Puerto Almendra (PA), and Zungarococha (ZG), using microscopic, molecular, and serological techniques to evaluate malaria transmission intensity. Statistical analysis, including multivariate-adjusted analysis, seroprevalence curves, and spatial clustering analysis, were performed to assess malaria prevalence, exposure, and risk factors. RESULTS: The survey revealed a high prevalence of asymptomatic infections (6% by microscopy and 18% by PCR), indicating that molecular methods are more sensitive for detecting asymptomatic infections. Seroprevalence varied significantly between villages, reflecting the heterogeneous malaria transmission dynamics. Multivariate analysis identified age, village, and limited bed net use as significant risk factors for malaria infection and species-specific exposure. Seroprevalence curves demonstrated community-specific patterns, with Llanchama and Puerto Almendra showing the highest seroconversion rates for both Plasmodium species. CONCLUSIONS: The study highlights the diverse nature of malaria transmission in the Loreto region, particularly nothing the pronounced heterogeneity as transmission rates decline, especially in residual malaria scenarios. The use of molecular and serological techniques enhances the detection of current infections and past exposure, aiding in the identification of epidemiological risk factors. These findings underscore the importance of using molecular and serological tools to characterize malaria transmission patterns in low-endemic areas, which is crucial for planning and implementing targeted interventions and elimination strategies. This is particularly relevant for initiatives like the Zero Malaria Plan in the Peruvian Amazon.

Astyanax mexicanus surface and cavefish chromosome-scale assemblies for trait variation discovery.

The ability of organisms to adapt to sudden extreme environmental changes produces some of the most drastic examples of rapid phenotypic evolution. The Mexican Tetra, Astyanax mexicanus, is abundant in the surface waters of northeastern Mexico, but repeated colonizations of cave environments have resulted in the independent evolution of troglomorphic phenotypes in several populations. Here, we present three chromosome-scale assemblies of this species, for one surface and two cave populations, enabling the first whole-genome comparisons between independently evolved cave populations to evaluate the genetic basis for the evolution of adaptation to the cave environment. Our assemblies represent the highest quality of sequence completeness with predicted protein-coding and noncoding gene metrics far surpassing prior resources and, to our knowledge, all long-read assembled teleost genomes, including zebrafish. Whole-genome synteny alignments show highly conserved gene order among cave forms in contrast to a higher number of chromosomal rearrangements when compared with other phylogenetically close or distant teleost species. By phylogenetically assessing gene orthology across distant branches of amniotes, we discover gene orthogroups unique to A. mexicanus. When compared with a representative surface fish genome, we find a rich amount of structural sequence diversity, defined here as the number and size of insertions and deletions as well as expanding and contracting repeats across cave forms. These new more complete genomic resources ensure higher trait resolution for comparative, functional, developmental, and genetic studies of drastic trait differences within a species.

Physical Rehabilitation and Mobilization in Patients Receiving Extracorporeal Life Support: A Systematic Review.

OBJECTIVES: We planned to synthesize evidence examining the potential efficacy and safety of performing physical rehabilitation and/or mobilization (PR&M) in adult patients receiving extracorporeal life support (ECLS). DATA SOURCES: We included any study that compared PR&M to no PR&M or among different PR&M strategies in adult patients receiving any ECLS for any indication and any cannulation. We searched seven electronic databases with no language limitations. STUDY SELECTION AND DATA EXTRACTION: Two reviewers, independently and in duplicate, screened all citations for eligibility. We used the Cochrane Risk of Bias 2 and Cochrane Risk Of Bias In Non-randomized Studies of Interventions tools to assess individual study risk of bias. Although we had planned for meta-analysis, this was not possible due to insufficient data, so we used narrative and tabular data summaries for presenting results. We assessed the overall certainty of the evidence for each outcome using the Grading of Recommendations Assessment, Development, and Evaluation framework. DATA SYNTHESIS: We included 17 studies that enrolled 996 patients. Most studies examined venovenous extracorporeal membrane oxygenation (ECMO) and/or venoarterial ECMO as a bridge to recovery in the ICU. We found an uncertain effect of high-intensity/active PR&M on mortality, duration of mechanical ventilation, ICU length of stay, hospital length of stay, or quality of life compared with low-intensity/passive PR&M in patients receiving ECLS (very low certainty due to very serious imprecision). There was similarly an uncertain effect on safety events including clinically important bleeding, spontaneous intracerebral hemorrhage, limb ischemia, accidental decannulation, or ECLS circuit dysfunction (very low certainty due to very serious risk of bias and imprecision). CONCLUSIONS: Based on the currently available summary of evidence, there is an uncertain effect of high-intensity/active PR&M on patient important outcomes or safety in patients receiving ECLS. Despite indirect data from other populations suggesting potential benefit of high-intensity PR&M in the ICU; further high-quality randomized trials evaluating the benefits and risks of physical therapy and/or mobilization in this population are needed.

Astyanax mexicanus surface and cavefish chromosome-scale assemblies for trait variation discovery.

The ability of organisms to adapt to sudden extreme environmental changes produces some of the most drastic examples of rapid phenotypic evolution. The Mexican Tetra, Astyanax mexicanus, is abundant in the surface waters of northeastern Mexico, but repeated colonizations of cave environments have resulted in the independent evolution of troglomorphic phenotypes in several populations. Here, we present three chromosome-scale assemblies of this species, for one surface and two cave populations, enabling the first whole-genome comparisons between independently evolved cave populations to evaluate the genetic basis for the evolution of adaptation to the cave environment. Our assemblies represent the highest quality of sequence completeness with predicted protein-coding and non-coding gene metrics far surpassing prior resources and, to our knowledge, all long-read assembled teleost genomes, including zebrafish. Whole genome synteny alignments show highly conserved gene order among cave forms in contrast to a higher number of chromosomal rearrangements when compared to other phylogenetically close or distant teleost species. By phylogenetically assessing gene orthology across distant branches of amniotes, we discover gene orthogroups unique to A. mexicanus. When compared to a representative surface fish genome, we find a rich amount of structural sequence diversity, defined here as the number and size of insertions and deletions as well as expanding and contracting repeats across cave forms. These new more complete genomic resources ensure higher trait resolution for comparative, functional, developmental, and genetic studies of drastic trait differences within a species.

Genome-Wide Association Study for Root Morphology and Phosphorus Acquisition Efficiency in Diverse Maize Panels.

Maximizing soil exploration through modifications of the root system is a strategy for plants to overcome phosphorus (P) deficiency. Genome-wide association with 561 tropical maize inbred lines from Embrapa and DTMA panels was undertaken for root morphology and P acquisition traits under low- and high-P concentrations, with 353,540 SNPs. P supply modified root morphology traits, biomass and P content in the global maize panel, but root length and root surface area changed differentially in Embrapa and DTMA panels. This suggests that different root plasticity mechanisms exist for maize adaptation to low-P conditions. A total of 87 SNPs were associated to phenotypic traits in both P conditions at -log10(p-value) ≥ 5, whereas only seven SNPs reached the Bonferroni significance. Among these SNPs, S9_137746077, which is located upstream of the gene GRMZM2G378852 that encodes a MAPKKK protein kinase, was significantly associated with total seedling dry weight, with the same allele increasing root length and root surface area under P deficiency. The C allele of S8_88600375, mapped within GRMZM2G044531 that encodes an AGC kinase, significantly enhanced root length under low P, positively affecting root surface area and seedling weight. The broad genetic diversity evaluated in this panel suggests that candidate genes and favorable alleles could be exploited to improve P efficiency in maize breeding programs of Africa and Latin America.

Genomic landscape of lung cancer in the young.

Background: Lung cancer in the young is a rare entity of great interest due to the high frequency of targetable mutations. In this study, we explored the genomic landscape of non-small cell lung cancer (NSCLC) in young patients and compared it with genetic alterations in older patients. Methods: Comparative study of the genomic profile of NSCLC young (≤40 years old) vs older patients (>40 years old) from Instituto Nacional de Enfermedades Neoplásicas (INEN) in Lima, Peru. Archival paraffin-embedded tumor samples were profiled with FoundationOne CDx assay to identify short variants alterations (insertions and deletions), copy number variations (CNV), tumor mutational burden and microsatellite instability in 324 driver genes and rearrangements in 28 commonly rearranged genes. A targetable alteration was defined as any alteration in a driver oncogene for which an FDA approved therapy existed at the time of study enrollment. Results: Overall, 62 tumors were profiled, 32 from young and 30 from older patients. All clinicopathological features (smoking status, clinical stage, and histology) were similar between groups, except for gender (65.6% of females in the younger group vs 40% in the older group, P=0.043). At least one actionable mutation was present in 84.4% and 83.3% in younger and older patients, respectively. Alteration rates in the main genes were: BRAF, 3.1%(n=1) vs 0%; EGFR, 46.9% (n=15) vs 43.3% (n=13); ERBB2, 12.5% (n=4) vs 16.7% (n=5); KRAS, 15.6% (n=5) vs 16.7% (n=5); ALK, 6.3% (n=2) vs 3.3% (n=1); RET, 0.0% vs 3.3% (n=1); ROS1, 3.1% (n=1) vs 3.3% (n=1); NTRK1, 0.0% vs 3.3% (n=1) and MET, 3.1% (n=1) vs 13.3% (n=4). Mean TMB was 4.04 Mut/Mb (SD ± 3.98) for young vs 8.06 Mut/Mb (SD ± 9.84) for older patients (P=0.016). There were not significant differences in CNV, frequency of gene rearrangements, or microsatellites instability. Conclusion: NSCLC in the young in our cohort was characterized by a high frequency of actionable genetic aberrations and a low TMB, which was also true for our older patients. The enrichment of actionable mutations in young patients described in other reports might be attributed to differences in the etiology and clinicopathological characteristics between younger and older patients and therefore not be applicable to all populations.

An adaptive teosinte mexicana introgression modulates phosphatidylcholine levels and is associated with maize flowering time.

Native Americans domesticated maize (Zea mays ssp. mays) from lowland teosinte parviglumis (Zea mays ssp. parviglumis) in the warm Mexican southwest and brought it to the highlands of Mexico and South America where it was exposed to lower temperatures that imposed strong selection on flowering time. Phospholipids are important metabolites in plant responses to low-temperature and phosphorus availability and have been suggested to influence flowering time. Here, we combined linkage mapping with genome scans to identify High PhosphatidylCholine 1 (HPC1), a gene that encodes a phospholipase A1 enzyme, as a major driver of phospholipid variation in highland maize. Common garden experiments demonstrated strong genotype-by-environment interactions associated with variation at HPC1, with the highland HPC1 allele leading to higher fitness in highlands, possibly by hastening flowering. The highland maize HPC1 variant resulted in impaired function of the encoded protein due to a polymorphism in a highly conserved sequence. A meta-analysis across HPC1 orthologs indicated a strong association between the identity of the amino acid at this position and optimal growth in prokaryotes. Mutagenesis of HPC1 via genome editing validated its role in regulating phospholipid metabolism. Finally, we showed that the highland HPC1 allele entered cultivated maize by introgression from the wild highland teosinte Zea mays ssp. mexicana and has been maintained in maize breeding lines from the Northern United States, Canada, and Europe. Thus, HPC1 introgressed from teosinte mexicana underlies a large metabolic QTL that modulates phosphatidylcholine levels and has an adaptive effect at least in part via induction of early flowering time.

A chromosome-level genome of Astyanax mexicanus surface fish for comparing population-specific genetic differences contributing to trait evolution.

Identifying the genetic factors that underlie complex traits is central to understanding the mechanistic underpinnings of evolution. Cave-dwelling Astyanax mexicanus populations are well adapted to subterranean life and many populations appear to have evolved troglomorphic traits independently, while the surface-dwelling populations can be used as a proxy for the ancestral form. Here we present a high-resolution, chromosome-level surface fish genome, enabling the first genome-wide comparison between surface fish and cavefish populations. Using this resource, we performed quantitative trait locus (QTL) mapping analyses and found new candidate genes for eye loss such as dusp26. We used CRISPR gene editing in A. mexicanus to confirm the essential role of a gene within an eye size QTL, rx3, in eye formation. We also generated the first genome-wide evaluation of deletion variability across cavefish populations to gain insight into this potential source of cave adaptation. The surface fish genome reference now provides a more complete resource for comparative, functional and genetic studies of drastic trait differences within a species.

The Impact of Physical Activity on the Prevention of Type 2 Diabetes: Evidence and Lessons Learned From the Diabetes Prevention Program, a Long-Standing Clinical Trial Incorporating Subjective and Objective Activity Measures.

OBJECTIVE: Across the Diabetes Prevention Program (DPP) follow-up, cumulative diabetes incidence remained lower in the lifestyle compared with the placebo and metformin randomized groups and could not be explained by weight. Collection of self-reported physical activity (PA) (yearly) with cross-sectional objective PA (in follow-up) allowed for examination of PA and its long-term impact on diabetes prevention. RESEARCH DESIGN AND METHODS: Yearly self-reported PA and diabetes assessment and oral glucose tolerance test results (fasting glucose semiannually) were collected for 3,232 participants with one accelerometry assessment 11-13 years after randomization (n = 1,793). Mixed models determined PA differences across treatment groups. The association between PA and diabetes incidence was examined using Cox proportional hazards models. RESULTS: There was a 6% decrease (Cox proportional hazard ratio 0.94 [95% CI 0.92, 0.96]; P < 0.001) in diabetes incidence per 6 MET-h/week increase in time-dependent PA for the entire cohort over an average of 12 years (controlled for age, sex, baseline PA, and weight). The effect of PA was greater (12% decrease) among participants less active at baseline (<7.5 MET-h/week) (n = 1,338) (0.88 [0.83, 0.93]; P < 0.0001), with stronger findings for lifestyle participants. Lifestyle had higher cumulative PA compared with metformin or placebo (P < 0.0001) and higher accelerometry total minutes per day measured during follow-up (P = 0.001 and 0.047). All associations remained significant with the addition of weight in the models. CONCLUSIONS: PA was inversely related to incident diabetes in the entire cohort across the study, with cross-sectional accelerometry results supporting these findings. This highlights the importance of PA within lifestyle intervention efforts designed to prevent diabetes and urges health care providers to consider both PA and weight when counseling high-risk patients.

Reproducibility of Dietary Intake Measurement From Diet Diaries, Photographic Food Records, and a Novel Sensor Method.

Objective: No data currently exist on the reproducibility of photographic food records compared to diet diaries, two commonly used methods to measure dietary intake. Our aim was to examine the reproducibility of diet diaries, photographic food records, and a novel electronic sensor, consisting of counts of chews and swallows using wearable sensors and video analysis, for estimating energy intake. Method: This was a retrospective analysis of data from a previous study, in which 30 participants (15 female), aged 29 ± 12 y and having a BMI of 27.9 ± 5.5, consumed three identical meals on different days. Four different methods were used to estimate total mass and energy intake on each day: (1) weighed food record; (2) photographic food record; (3) diet diary; and (4) novel mathematical model based on counts of chews and swallows (CCS models) obtained via the use of electronic sensors and video monitoring system. The study staff conducted weighed food records for all meals, took pre- and post-meal photographs, and ensured that diet diaries were completed by participants at the end of each meal. All methods were compared against the weighed food record, which was used as the reference method. Results: Reproducibility was significantly different between the diet diary and photographic food record for total energy intake (p = 0.004). The photographic record had greater reproducibility vs. the diet diary for all parameters measured. For total energy intake, the novel sensor method exhibited good reproducibility (repeatability coefficient (RC) of 59.9 (45.9, 70.4), which was better than that for the diet diary [RC = 79.6 (55.5, 103.3)] but not as repeatable as the photographic method [RC = 43.4 (32.1, 53.9)]. Conclusion: Photographic food records offer superior precision to the diet diary and, therefore, would be valuable for longitudinal studies with repeated measures of dietary intake. A novel electronic sensor also shows promise for the collection of longitudinal dietary intake data.

A Multimetric Health Literacy Analysis of Online Information for Gluteal Augmentation With Fat Grafting.

BACKGROUND AND OBJECTIVES: According to the American Society of Plastic Surgeons the number of gluteal augmentations with fat grafting, colloquially known as the "Brazilian buttock lift" (BBL), doubled from 2014 to 2018. Recent studies have demonstrated that gluteal augmentation with fat grafting has a higher mortality rate when compared with other esthetic surgeries. We hypothesize that online patient-directed information for gluteal augmentation are overly complex, written at an elevated reading grade level, with incomplete or no information regarding associated surgical risks. OBJECTIVE: To perform an objective appraisal of the most popular online patient education materials for gluteal augmentation surgery and explore potential interventions for improving material quality. METHODS: An online Google search using the term "Brazilian butt lift" was performed and the top 10 websites providing relevant information were identified. Readability for each website was determined using Readability Studio. Understandability, actionability and cultural sensitivity was assessed with validated tools by 2 independent raters. RESULTS: The top 10 websites were written at a mean reading grade level of 13.0, appropriate for a high school graduate. No website was written at the American Medical Association and the National Institutes of Health recommended 6th to 8th grade reading level. Mean understandability and actionability scores of 51% and 18.9%, respectively, suggest significant room for improvement. The average cultural sensitivity assessment tool score was 2.30, below the recommended threshold for acceptability of 2.5. Ninety percent of all websites did not meet the threshold for cultural acceptability. CONCLUSIONS: Online patient education materials for gluteal augmentation with fat grafting were written at an inappropriately elevated reading grade level and were overly complex, did not promote reader action, and were not sensitive to the needs of the target demographic.

Abnormal Exercise Test or CVD History on Weight Loss or Fitness: the Look AHEAD Trial.

PURPOSE: Obesity and type 2 diabetes are associated with an increased risk of cardiovascular disease (CVD) and the combination of weight loss and increased physical exercise are commonly recommended to reduce CVD. This study examined whether people with obesity and type 2 diabetes with an abnormal graded exercise tolerance test (GXT) or a history of CVD would have less success in achieving weight loss and improved fitness, compared to adults without these conditions. METHODS: The Look AHEAD Study examined whether an intensive lifestyle intervention (ILI) compared with diabetes support and education (DSE) reduced cardiovascular events in adults with overweight/obesity and type 2 diabetes. Participants underwent a baseline maximal GXT and provided medical history data. Weight loss and fitness change were examined in 5011 participants over four years in those with or without an abnormal baseline GXT and/or history of CVD. RESULTS: After four years, weight loss in both ILI and DSE were significantly greater in those without a prior history of CVD than in those with a CVD history (6.69% vs 5.98%, p=0.02, in ILI and 0.73 vs -.07% (weight gain), p=0.01, in DSE). Likewise, those without a prior history of CVD experienced greater improvements in fitness in both ILI and DSE relative to those with a history of CVD. Having an abnormal GXT at baseline did not affect weight loss or fitness. CONCLUSIONS: A history of CVD at baseline modestly lessened weight loss and fitness changes at 4 years, whereas having any abnormality on the baseline GXT did not affect these outcomes. Thus, weight loss and improved fitness are achievable in adults with a history of CVD or ECG abnormalities.

Trypan Blue for the Assessment of Filtering Bleb Function During Cataract Surgery.

PURPOSE: Phacoemulsification has been cited as a possible cause of bleb failure in eyes with prior trabeculectomy. No method has been developed to directly evaluate the risk of bleb failure after phacoemulsification. We investigate the use of trypan blue during cataract surgery in the setting of a preexisting trabeculectomy to evaluate the functional status of the bleb and predict postoperative bleb function. MATERIALS AND METHODS: In total, 14 patients contributing 1 eye each with a history of prior trabeculectomy with mitomycin C undergoing phacoemulsification with intraocular lens implantation were enrolled in this prospective, nonrandomized clinical trial. At the time of phacoemulsification, trypan blue was instilled into the anterior chamber before capsulorhexis creation. Staining of the bleb was grouped as being mild or diffuse using intraoperative photographs. These eyes were followed for 1 year postoperatively and evaluated for intraocular pressure (IOP) control. RESULTS: The change in IOP was not significantly different between the 2 groups (P=0.14). A trend towards greater need for IOP-lowering medications was noted (P<0.10) in eyes with mild bleb staining. No statistically significant difference in rates of decreased bleb function was noted at 1-year follow-up after phacoemulsification. CONCLUSION: The intensity of bleb staining with trypan blue during phacoemulsification is not associated with changes in IOP postoperatively. A trend towards decreased need for IOP-lowering medications was noted in eyes with diffuse bleb staining at 1 year after cataract surgery.

Cetuximab plus carboplatin and paclitaxel with or without bevacizumab versus carboplatin and paclitaxel with or without bevacizumab in advanced NSCLC (SWOG S0819): a randomised, phase 3 study.

BACKGROUND: EGFR antibodies have shown promise in patients with advanced non-small-cell lung cancer (NSCLC), particularly with squamous cell histology. We hypothesised that EGFR copy number by fluorescence in-situ hybridisation (FISH) can identify patients most likely to benefit from these drugs combined with chemotherapy and we aimed to explore the activity of cetuximab with chemotherapy in patients with advanced NSCLC who are EGFR FISH-positive. METHODS: We did this open-label, phase 3 study (SWOG S0819) at 277 sites in the USA and Mexico. We randomly assigned (1:1) eligible patients with treatment-naive stage IV NSCLC to receive paclitaxel (200 mg/m2; every 21 days) plus carboplatin (area under the curve of 6 by modified Calvert formula; every 21 days) or carboplatin plus paclitaxel and bevacizumab (15 mg/kg; every 21 days), either with cetuximab (250 mg/m2 weekly after loading dose; cetuximab group) or without (control group), stratified by bevacizumab treatment, smoking status, and M-substage using a dynamic-balancing algorithm. Co-primary endpoints were progression-free survival in patients with EGFR FISH-positive cancer and overall survival in the entire study population. We analysed clinical outcomes with the intention-to-treat principle and analysis of safety outcomes included patients who received at least one dose of study drug. This study is registered with ClinicalTrials.gov (number NCT00946712). FINDINGS: Between Aug 13, 2009, and May 30, 2014, we randomly assigned 1313 patients to the control group (n=657; 277 with bevacizumab and 380 without bevacizumab in the intention-to-treat population) or the cetuximab group (n=656; 283 with bevacizumab and 373 without bevacizumab in the intention-to-treat population). EGFR FISH was assessable in 976 patients and 400 patients (41%) were EGFR FISH-positive. The median follow-up for patients last known to be alive was 35·2 months (IQR 22·9-39·9). After 194 progression-free survival events in the cetuximab group and 198 in the control group in the EGFR FISH-positive subpopulation, progression-free survival did not differ between treatment groups (hazard ratio [HR] 0·92, 95% CI 0·75-1·12; p=0·40; median 5·4 months [95% CI 4·5-5·7] vs 4·8 months [3·9-5·5]). After 570 deaths in the cetuximab group and 593 in the control group, overall survival did not differ between the treatment groups in the entire study population (HR 0·93, 95% CI 0·83-1·04; p=0·22; median 10·9 months [95% CI 9·5-12·0] vs 9·2 months [8·7-10·3]). In the prespecified analysis of EGFR FISH-positive subpopulation with squamous cell histology, overall survival was significantly longer in the cetuximab group than in the control group (HR 0·58, 95% CI 0·36-0·86; p=0·0071), although progression-free survival did not differ between treatment groups in this subgroup (0·68, 0·46-1·01; p=0·055). Overall survival and progression-free survival did not differ among patients who were EGFR FISH non-positive with squamous cell histology (HR 1·04, 95% CI 0·78-1·40; p=0·77; and 1·02, 0·77-1·36; p=0·88 respectively) or patients with non-squamous histology regardless of EGFR FISH status (for EGFR FISH-positive 0·88, 0·68-1·14; p=0·34; and 0·99, 0·78-1·27; p=0·96; respectively; and for EGFR FISH non-positive 1·00, 0·85-1·17; p=0·97; and 1·03, 0·88-1·20; p=0·69; respectively). The most common grade 3-4 adverse events were decreased neutrophil count (210 [37%] in the cetuximab group vs 158 [25%] in the control group), decreased leucocyte count (103 [16%] vs 74 [20%]), fatigue (81 [13%] vs 74 [20%]), and acne or rash (52 [8%] vs one [<1%]). 59 (9%) patients in the cetuximab group and 31 (5%) patients in the control group had severe adverse events. Deaths related to treatment occurred in 32 (6%) patients in the cetuximab group and 13 (2%) patients in the control group. INTERPRETATION: Although this study did not meet its primary endpoints, prespecified subgroup analyses of patients with EGFR FISH-positive squamous-cell carcinoma cancers are encouraging and support continued evaluation of anti-EGFR antibodies in this subpopulation. FUNDING: National Cancer Institute and Eli Lilly and Company.

Ivermectin susceptibility, sporontocidal effect, and inhibition of time to re-feed in the Amazonian malaria vector Anopheles darlingi.

BACKGROUND: Outdoor malaria transmission hinders malaria elimination efforts in the Amazon region and novel vector control tools are needed. Ivermectin mass drug administration (MDA) to humans kills wild Anopheles, targets outdoor-feeding vectors, and can suppress malaria parasite transmission. Laboratory investigations were performed to determine ivermectin susceptibility, sporontocidal effect and inhibition of time to re-feed for the primary Amazonian malaria vector, Anopheles darlingi. METHODS: To assess ivermectin susceptibility, various concentrations of ivermectin were mixed in human blood and fed to An. darlingi. Mosquito survival was monitored daily for 7 days and a non-linear mixed effects model with Probit analysis was used to calculate lethal concentrations of ivermectin that killed 50% (LC50), 25% (LC25) and 5% (LC5) of mosquitoes. To examine ivermectin sporonticidal effect, Plasmodium vivax blood samples were collected from malaria patients and offered to mosquitoes without or with ivermectin at the LC50, LC25 or LC5. To assess ivermectin inhibition of mosquito time to re-feed, concentrations of ivermectin predicted to occur after a single oral dose of 200 µg/kg ivermectin were fed to An. darlingi. Every day for 12 days thereafter, individual mosquitoes were given the opportunity to re-feed on a volunteer. Any mosquitoes that re-blood fed or died were removed from the study. RESULTS: Ivermectin significantly reduced An. darlingi survivorship: 7-day-LC50 = 43.2 ng/ml [37.5, 48.6], -LC25 = 27.8 ng/ml [20.4, 32.9] and -LC5 = 14.8 ng/ml [7.9, 20.2]. Ivermectin compound was sporontocidal to P. vivax in An. darlingi at the LC50 and LC25 concentrations reducing prevalence by 22.6 and 17.1%, respectively, but not at the LC5. Oocyst intensity was not altered at any concentration. Ivermectin significantly delayed time to re-feed at the 4-h (48.7 ng/ml) and 12-h (26.9 ng/ml) concentrations but not 36-h (10.6 ng/ml) or 60-h (6.3 ng/ml). CONCLUSIONS: Ivermectin is lethal to An. darlingi, modestly inhibits sporogony of P. vivax, and delays time to re-feed at concentrations found in humans up to 12 h post drug ingestion. The LC50 value suggests that a higher than standard dose (400-µg/kg) is necessary to target An. darlingi. These results suggest that ivermectin MDA has potential in the Amazon region to aid malaria elimination efforts.

Plagiarism, Cheating and Research Integrity: Case Studies from a Masters Program in Peru.

Plagiarism is a serious, yet widespread type of research misconduct, and is often neglected in developing countries. Despite its far-reaching implications, plagiarism is poorly acknowledged and discussed in the academic setting, and insufficient evidence exists in Latin America and developing countries to inform the development of preventive strategies. In this context, we present a longitudinal case study of seven instances of plagiarism and cheating arising in four consecutive classes (2011-2014) of an Epidemiology Masters program in Lima, Peru, and describes the implementation and outcomes of a multifaceted, "zero-tolerance" policy aimed at introducing research integrity. Two cases involved cheating in graded assignments, and five cases correspond to plagiarism in the thesis protocol. Cases revealed poor awareness of high tolerance to plagiarism, poor academic performance, and widespread writing deficiencies, compensated with patchwriting and copy-pasting. Depending on the events' severity, penalties included course failure (6/7) and separation from the program (3/7). Students at fault did not engage in further plagiarism. Between 2011 and 2013, the Masters program sequentially introduced a preventive policy consisting of: (i) intensified research integrity and scientific writing education, (ii) a stepwise, cumulative writing process; (iii) honor codes; (iv) active search for plagiarism in all academic products; and (v) a "zero-tolerance" policy in response to documented cases. No cases were detected in 2014. In conclusion, plagiarism seems to be widespread in resource-limited settings and a greater response with educational and zero-tolerance components is needed to prevent it.

Physical activity and experience of total knee replacement in patients one to four years postsurgery in the dominican republic: a qualitative study.

OBJECTIVE: Musculoskeletal disorders are the second leading cause of years lived with disability globally. Total knee replacement (TKR) offers patients with advanced arthritis relief from pain and the opportunity to return to physical activity. We investigated the impact of TKR on physical activity for patients in a developing nation. METHODS: As part of the Operation Walk Boston surgical mission program, we interviewed 18 Dominican patients (78% women) who received TKR about their level of physical activity after surgery. Qualitative interviews were conducted in Spanish, and English transcripts were analyzed using content analysis. RESULTS: Most patients found that TKR increased their participation in physical activities in several life domains, such as occupational or social pursuits. Some patients limited their own physical activities due to uncertainty about medically appropriate levels of joint use and postoperative physical activity. Many patients noted positive effects of TKR on mood and mental health. For most patients in the study, religion offered a framework for understanding their receipt of and experience with TKR. CONCLUSION: Our findings underscore the potential of TKR to permit patients in the developing world to return to physical activities. This research also demonstrates the influence of patients' education, culture, and religion on patients' return to physical activity. As the global burden of musculoskeletal disease increases, it is important to characterize the impact of activity limitation on patients' lives in diverse settings and the potential for surgical intervention to ease the burden of chronic arthritis.

Functional results following surgical repair of simultaneous bilateral quadriceps tendon ruptures.

BACKGROUND: Unilateral quadriceps tendon ruptures are common conditions treated by orthopedic surgeons. There is a paucity of information concerning functional outcomes in bilateral tendon ruptures. The aim of this study is to assess a series of 5 cases with simultaneous quadriceps tendon ruptures that underwent acute surgical repair with the purpose of identifying the functional outcomes as compared with unilateral injuries. We hypothesize that patients with bilateral quadriceps tendon ruptures have worse functional outcomes than patients with unilateral ruptures. METHODS: Five cases of bilateral quadriceps tendon ruptures were identified. All patients underwent acute surgical extensor tendon repair employing a 3-patellar hole and a locked, running, nonabsorbable suture technique followed by a 6-week period of immobilization and bracing for 10 to 12 weeks. Mechanism of injury, medical history, social history, operative report, and postoperative exam were recorded with a minimum 1-year follow-up. In addition, each patient completed a subjective International Knee Documentation Committee (IKDC) score at 18 months. Five patients with unilateral injuries and with similar medical history were included as age-matched controls. RESULTS: The mean age for the bilateral group was 54.8 years (range, 44-68 years). Mean postoperative knee flexion was 129 degrees and all patients had active, resisted knee extension. Only 1 patient had a medical comorbidity (diabetes mellitus). The mean IKDC score (mean follow-up, 25.4 months; range, 22-29 months) was 71.9 (range, 34.4 to 91.6), whereas the age-matched control group had a mean IKDC score of 88.3 (P = 0.23). There was no statistical significance between the 2 groups with regard to range of motion (P = 0.24), IKDC score, and return to activity (P = 0.29). CONCLUSION: Patients with early surgical repair of bilateral, simultaneous extensor mechanism ruptures exhibit adequate recovery and return to a high level of function. Our patients were younger than those reported in the literature and had minimal comorbidities. The IKDC scores reflected good outcomes in the bilateral rupture group, albeit lower than in the unilateral group.

Bilateral wrist drop complicating axillary crutches mobilization in a young adult / Mano péndula bilateral que complica la movilización con muletas axilares en un adulto joven

OBJECTIVE: Axillary crutches are simple rehabilitative devices that are globally used temporarily or permanently to assist in ambulation of patients and rarely present with complication. This report is about bilateral wrist drop incidentally noticed in a young adult patient mobilized on axillary crutches after internal fixation of a simple right tibia fracture. METHODS: The fracture was fixed by intramedullary nailing and the patient was mobilized on axillary crutches. At six weeks, patient fearfully refused to be commenced on partial weight bearing and at 12 weeks after surgery he was noticed to be totally weightbearing on the bars of the appropriately long axillary crutches and had developed bilateral wrist drop. There was radiological evidence of healing at the fracture sites. Treatment included mobilization on one elbow crutch on the left, physical therapy and nerve stimulation. RESULTS: At six weeks of physiotherapy, the power of the dorsiflexors of the wrists had recovered completely. CONCLUSION: Bilateral posterior cord palsy of brachial plexus could occur even in young healthy patients but total recovery could occur if the diagnosis and treatment are prompt. Patients should be told in unequivocal terms not to weight bear directly on axillary bars.

OBJETIVO: Las muletas axilares son simples dispositivos de rehabilitación que se utilizan en todo el mundo de manera temporal o permanentemente para ayudar a caminar a los pacientes, y raramente presentan complicación. Este trabajo trata de la mano péndula o mano caída, observada incidentalmente en un paciente adulto joven movilizado en muletas axilares, después de la fijación interna de una fractura simple de la tibia derecha. MÉTODOS: La fractura fue fijada mediante clavo intramedular, y el paciente fue movilizado con muletas axilares. A las seis semanas, el paciente se negó temeroso a la iniciación para sostener parcialmente todo su peso con ayuda de muletas, y a las 12 semanas después de la cirugía, se le vio sostener todo su peso sobre las barras de las muletas axilares de longitud adecuada, y había desarrollado mano péndula bilateral. Había evidencia radiológica de curación en los sitios de fractura. El tratamiento incluyó la movilización con una muleta de codo a la izquierda, terapia física, y estimulación nerviosa. RESULTADOS: A las seis semanas de fisioterapia, la capacidad de los dorsiflexores de las muñecas se había recuperado completamente. CONCLUSIÓN: La parálisis del fascículo posterior bilateral del plexo braquial podría ocurrir incluso en pacientes jóvenes sanos, pero la recuperación total podría ocurrir si el diagnóstico y el tratamiento se hacen a tiempo. A los pacientes se les debe decir en términos inequívocos que no deben soportar todo su peso directamente en las barras axilares.

A comparison of energy expenditure estimation of several physical activity monitors.

INTRODUCTION: Accurately and precisely estimating free-living energy expenditure (EE) is important for monitoring energy balance and quantifying physical activity. Recently, single and multisensor devices have been developed that can classify physical activities, potentially resulting in improved estimates of EE. PURPOSE: This study aimed to determine the validity of EE estimation of a footwear-based physical activity monitor and to compare this validity against a variety of research and consumer physical activity monitors. METHODS: Nineteen healthy young adults (10 men, 9 women) completed a 4-h stay in a room calorimeter. Participants wore a footwear-based physical activity monitor as well as Actical, ActiGraph, IDEEA, DirectLife, and Fitbit devices. Each individual performed a series of postures/activities. We developed models to estimate EE from the footwear-based device, and we used the manufacturer's software to estimate EE for all other devices. RESULTS: Estimated EE using the shoe-based device was not significantly different than measured EE (mean ± SE; 476 ± 20 vs 478 ± 18 kcal, respectively) and had a root-mean-square error of 29.6 kcal (6.2%). The IDEEA and the DirectLlife estimates of EE were not significantly different than the measured EE, but the ActiGraph and the Fitbit devices significantly underestimated EE. Root-mean-square errors were 93.5 (19%), 62.1 kcal (14%), 88.2 kcal (18%), 136.6 kcal (27%), 130.1 kcal (26%), and 143.2 kcal (28%) for Actical, DirectLife, IDEEA, ActiGraph, and Fitbit, respectively. CONCLUSIONS: The shoe-based physical activity monitor provides a valid estimate of EE, whereas the other physical activity monitors tested have a wide range of validity when estimating EE. Our results also demonstrate that estimating EE based on classification of physical activities can be more accurate and precise than estimating EE based on total physical activity.