Oncology phase I trial design and conduct: time for a change - MDICT Guidelines 2022.

In 2021, the Food and Drug Administration Oncology Center of Excellence announced Project Optimus focusing on dose optimization for oncology drugs. The Methodology for the Development of Innovative Cancer Therapies (MDICT) Taskforce met to review and discuss the optimization of dosage for oncology trials and to develop a practical guide for oncology phase I trials. Defining a single recommended phase II dose based on toxicity may define doses that are neither the most effective nor the best tolerated. MDICT recommendations address the need for robust non-clinical data which are needed to inform trial design, as well as an expert team including statisticians and pharmacologists. The protocol must be flexible and adaptive, with clear definition of all endpoints. Health authorities should be consulted early and regularly. Strategies such as randomization, intrapatient dose escalation, and real-world eligibility criteria are encouraged whereas serial tumor sampling is discouraged in the absence of a strong rationale and appropriately validated assay. Endpoints should include consideration of all longitudinal toxicity. The phase I dose escalation trial should define the recommended dose range for later testing in randomized phase II trials, rather than a single recommended phase II dose, and consider scenarios where different populations may require different dosages. The adoption of these recommendations will improve dosage selection in early clinical trials of new anticancer treatments and ultimately, outcomes for patients.

Clinical utility of circulating tumor DNA sequencing with a large panel: a National Center for Precision Medicine (PRISM) study.

BACKGROUND: Circulating tumor DNA (ctDNA) sequencing is a promising approach for tailoring therapy in patients with cancer. We report hereby the results from a prospective study where we investigated the impact of comprehensive molecular profiling of ctDNA in patients with advanced solid tumors. PATIENTS AND METHODS: Genomic analysis was performed using the FoundationOne Liquid CDx Assay [324 genes, tumor mutational burden (TMB), microsatellite instability status]. Each individual genomic report was reviewed and discussed weekly by a multidisciplinary tumor board (MTB). Actionable targets were classified by ESMO Scale for Clinical Actionability of Molecular Targets (ESCAT) tier leading to molecular-based treatment suggestions wherever it was possible. RESULTS: Between December 2020 and November 2021, 1772 patients with metastatic solid tumors underwent molecular profiling. Median time to assay results was 12 days. Results were contributive for 1658 patients (94%). At least one actionable target was detected in 1059 patients (64%) with a total of 1825 actionable alterations including alteration of the DNA damage repair response pathway (n = 336, 18%), high TMB (>16 mutations/Mb; n = 243, 13%), PIK3CA mutations (n = 150, 8%), ERBB family pathway alterations (n = 127, 7%), PTEN alterations (n = 95, 5%), FGFR alterations (n = 67, 4%) and MET activations (n = 13, 0.7%). The MTB recommended a matched therapy for 597 patients (56%) with a total of 819 therapeutic orientations: clinical trials (n = 639, 78%), off-label/compassionate use (n = 81, 10%), approved drug (n = 51, 6%), and early access program (n = 48, 6%). In total, 122 patients (21%) were treated. Among the assessable patients (n = 107), 4 (4%) had complete response, 35 (33%) had partial response, 27 (25%) had stable disease, and 41 (38%) a progressive disease as best response. The median progression-free survival and median overall survival were 4.7 months (95% confidence interval 2.7-6.7 months) and 8.3 months (95% confidence interval 4.7-11.9 months) respectively. CONCLUSIONS: ctDNA sequencing with a large panel is an efficient approach to match patients with advanced cancer with targeted therapies.

Single-cell DNA-seq depicts clonal evolution of multiple driver alterations in osimertinib-resistant patients.

BACKGROUND: The development of targeted agents, such as osimertinib for EGFR-mutated non-small-cell lung cancer (NSCLC), has drastically improved patient outcome, but tumor resistance eventually always occurs. In osimertinib-resistant NSCLC, the emergence of a second molecular driver alteration (such as ALK, RET, FGFR3 fusions or BRAF, KRAS mutations) has been described. Whether those alterations and the activating EGFR mutations occur within a single cancer cell or in distinct cell populations is largely debated. PATIENTS AND METHODS: Tumor sequencing was used to identify the acquired resistance mechanisms to osimertinib in the MATCH-R trial (NCT0251782). We implemented single-cell next-generation sequencing to investigate tumor heterogeneity on patient's frozen tissues in which multiple alterations have been identified. Patient-derived models, cell lines, and patient-derived xenografts were exposed to specific inhibitors to investigate combination treatment strategies. RESULTS: Among the 45 patients included in MATCH-R who progressed on osimertinib, 9 developed a second targetable alteration (n = 2 FGFR3-TACC3, n = 1 KIF5B-RET, n = 1 STRN-ALK fusions; n = 2 BRAFV600E, n = 1 KRASG12V, n = 1 KRASG12R, n = 1 KRASG12D mutations). Single-cell analysis revealed that the two driver alterations coexist within one single cancer cell in the four patients whose frozen samples were fully contributive. A high degree of heterogeneity within samples and sequential acquisitions of molecular events were highlighted. A combination treatment concomitantly targeting the two driver alterations was required on the corresponding patient-derived models to restore cell sensitivity, which was consistent with clinical data showing efficacy of brigatinib in the patient with ALK fusion after progression to osimertinib and crizotinib administered sequentially. CONCLUSIONS: Distinct molecular driver alterations at osimertinib resistance coexist with initial EGFR mutations in single cancer cells. The clonal evolution of cancer cell populations emphasized their heterogeneity leading to osimertinib relapse. Combining two targeted treatments is effective to achieve clinical benefit.

Effect of calving age on genetic evaluation of milk yield in Holstein cattle.

The aim of this study was to evaluate the effect of including calving age (CA) on genetic evaluation models for Holstein cattle. The evaluated models included the permanent environment, the sire-herd interactions, and the animals and residual effects as random. The fixed effects included the average production of milk, fat, and protein and the herd-year-season effect. The analyzed data included 603,521 records of milk production (in kg) corresponding to 438,098 animals from 527 herds. Additionally, there were 179,122 records of fat and protein components, corresponding to 148,930 animals from 137 herds. The records were classified by first lactation only (FL) and all available lactations (AL) for validation test (VT). The FL records corresponded to 275,487 milk production records with a mean of 10,874.1 ± 2773.9 kg at a mean CA of 25.6 ± 4.2 months. For FL, the milk components consisted of 78,955 records with a mean fat production of 392.86 ± 89.9 kg, a mean protein production of 362.8 ± 74.9 kg and a mean CA of 25.2 ± 4.1 months. For AL, the number of records was 603,521 for milk production with a mean of 10,802.8 ± 2905.9 kg and a mean CA of 35.6 ± 11.5 months. For the milk components, there were 179,122 records with a mean of 36.1 ± 9.5 months for CA and 388.3 ± 98.4 kg and 356.7 ± 82.6 kg for fat and protein, respectively. Three models were compared: the base model (M0) described above, and two alternative models that included CA in a linear and quadratic form (M1 and M2, respectively). Estimations of the variance components (VC) and breeding value (BV) were obtained using a repeatability animal model, with the same phenotypic and pedigree information used for all models. To select the best fit model for the data, a likelihood ratio test (LRtest) was used. A validation test (VT) was also applied to each model to evaluate the consistency of the genetic trends for females with information on AL and FL. The inclusion of CA in its linear form (M1) was the model that achieved the best results in the LRtest and an acceptable value for the VT. These results show that CA improves the model fit for BV prediction and reliability.

Few mitochondrial DNA sequences are inserted into the turkey (Meleagris gallopavo) nuclear genome: evolutionary analyses and informativity in the domestic lineage.

Mitochondrial DNA (mtDNA) insertions have been detected in the nuclear genome of many eukaryotes. These sequences are pseudogenes originated by horizontal transfer of mtDNA fragments into the nuclear genome, producing nuclear DNA sequences of mitochondrial origin (numt). In this study we determined the frequency and distribution of mtDNA-originated pseudogenes in the turkey (Meleagris gallopavo) nuclear genome. The turkey reference genome (Turkey_2.01) was aligned with the reference linearized mtDNA sequence using last. A total of 32 numt sequences (corresponding to 18 numt regions derived by unique insertional events) were identified in the turkey nuclear genome (size ranging from 66 to 1415 bp; identity against the modern turkey mtDNA corresponding region ranging from 62% to 100%). Numts were distributed in nine chromosomes and in one scaffold. They derived from parts of 10 mtDNA protein-coding genes, ribosomal genes, the control region and 10 tRNA genes. Seven numt regions reported in the turkey genome were identified in orthologues positions in the Gallus gallus genome and therefore were present in the ancestral genome that in the Cretaceous originated the lineages of the modern crown Galliformes. Five recently integrated turkey numts were validated by PCR in 168 turkeys of six different domestic populations. None of the analysed numts were polymorphic (i.e. absence of the inserted sequence, as reported in numts of recent integration in other species), suggesting that the reticulate speciation model is not useful for explaining the origin of the domesticated turkey lineage.

Genomic variability in Mexican chicken population using copy number variants.

BACKGROUND: Copy number variations are genome polymorphism that influence phenotypic variation and are an important source of genetic variation in populations. The aim of this study was to investigate genetic variability in the Mexican Creole chicken population using CNVs. RESULTS: The Hidden Markov Model of the PennCNV software detected a total of 1924 CNVs in the genome of the 256 samples processed with Axiom® Genome-Wide Chicken Genotyping Array (Affymetrix). The mapped CNVs comprised 1538 gains and 386 losses, resulting at population level in 1216 CNV regions (CNVRs), of which 959 gains, 226 losses and 31 complex (i.e. containing both losses and gains). The CNVRs covered a total of 47 Mb of the whole genome sequence length, corresponding to 5.12% of the chicken galGal4 autosome assembly. CONCLUSIONS: This study allowed a deep insight into the structural variation in the genome of unselected Mexican chicken population, which up to now has not been genetically characterized. The genomic study disclosed that the population, even if presenting extreme morphological variation, cannot be organized in differentiated genetic subpopulations. Finally this study provides a chicken CNV map based on the 600 K SNP chip array jointly with a genome-wide gene copy number estimates in a native unselected for more than 500 years chicken population.

Genome-wide association study for milk somatic cell score in holstein cattle using copy number variation as markers.

Mastitis, the most common and expensive disease in dairy cows, implies significant losses in the dairy industry worldwide. Many efforts have been made to improve genetic mastitis resistance in dairy populations, but low heritability of this trait made this process not as effective as desired. The purpose of this study was to identify genomic regions explaining genetic variation of somatic cell count using copy number variations (CNVs) as markers in the Holstein population, genotyped with the Illumina BovineHD BeadChip. We found 24 and 47 copy number variation regions significantly associated with estimated breeding values for somatic cell score (SCS_EBVs) using SVS 8.3.1 and PennCNV-CNVRuler software, respectively. The association analysis performed with these two software allowed the identification of 18 candidate genes (TERT, NOTCH1, SLC6A3, CLPTM1L, PPARα, BCL-2, ABO, VAV2, CACNA1S, TRAF2, RELA, ELF3, DBH, CDK5, NF2, FASN, EWSR1 and MAP3K11) that result classified in the same functional cluster. These genes are also part of two gene networks, whose genes share the 'stress', 'cell death', 'inflammation' and 'immune response' GO terms. Combining CNV detection/association analysis based on two different algorithms helps towards a more complete identification of genes linked to phenotypic variation of the somatic cell count.

Temperature dependence of the electronic structure of semiconductors and insulators.

The renormalization of electronic eigenenergies due to electron-phonon coupling (temperature dependence and zero-point motion effect) is sizable in many materials with light atoms. This effect, often neglected in ab initio calculations, can be computed using the perturbation-based Allen-Heine-Cardona theory in the adiabatic or non-adiabatic harmonic approximation. After a short description of the recent progresses in this field and a brief overview of the theory, we focus on the issue of phonon wavevector sampling convergence, until now poorly understood. Indeed, the renormalization is obtained numerically through a slowly converging q-point integration. For non-zero Born effective charges, we show that a divergence appears in the electron-phonon matrix elements at q → Γ, leading to a divergence of the adiabatic renormalization at band extrema. This problem is exacerbated by the slow convergence of Born effective charges with electronic wavevector sampling, which leaves residual Born effective charges in ab initio calculations on materials that are physically devoid of such charges. Here, we propose a solution that improves this convergence. However, for materials where Born effective charges are physically non-zero, the divergence of the renormalization indicates a breakdown of the adiabatic harmonic approximation, which we assess here by switching to the non-adiabatic harmonic approximation. Also, we study the convergence behavior of the renormalization and develop reliable extrapolation schemes to obtain the converged results. Finally, the adiabatic and non-adiabatic theories, with corrections for the slow Born effective charge convergence problem (and the associated divergence) are applied to the study of five semiconductors and insulators: α-AlN, ß-AlN, BN, diamond, and silicon. For these five materials, we present the zero-point renormalization, temperature dependence, phonon-induced lifetime broadening, and the renormalized electronic band structure.

Dysgnathia complex sine holoprosencephaly nor synotia: a case report and discussion of its nosology.

A severe mandibular hypoplasia and microstomy with intraoral anomalies including hypoglossia, fused gums, persistence of buccopharyngeal membrane, and laryngeal hypoplasia were noted in a female newborn with the dysgnathia complex (DC). Additionally, our proposita also presented natal teeth as a probably new finding. These clinical manifestations overlapped with those of the fourth report of hypomandibular faciocranial syndrome (HFS) (31), and given that both lack for craniosynostosis (pathognomonic of HFS), we considered that both represent a subtype of DC proposed as DC sine holoprosencephaly nor synotia (DCSHS). Differential characteristics between the DCSHS, the HFS, and the DC with holoprosencephaly sine synotia are reviewed and additionally, we discussed some aspects about the nosology of the DC.

Infections occurring following IL6 blockade for the management of cytokine release syndrome in onco-hematology patients.

BACKGROUND: Cytokine release syndrome (CRS) is a common adverse event of CAR T cell or bispecific antibody (bsAb) therapy. Anti-IL6/IL6R drugs are used in the management of auto-immune diseases. Some reports showed increased risk of bacterial infection in this context. In onco-hematology, there are few data about the occurrence of infection after administration of an anti-IL6/IL6R for CRS. METHODS: We retrospectively reviewed all consecutive patients treated in Gustave Roussy Cancer Campus between 2018 and 2021, who received anti-IL6/IL6R for CRS due to bsAb in phase I clinical trials or adoptive cellular therapy (ACT). We constituted a control group including all the patients treated in the same clinical trials or standard of care ACT, naïve of anti-IL6/IL6R. RESULTS: Fifty-two patients have been included. In the anti-IL6/IL6R group (n = 26), five patients developed a grade 2 to 5 infection within a month after anti-IL6/IL6R treatment, including two grade 5 infections. In the control group (n = 26), only one patient had a grade 3 infection. The two patients who had grade 5 infections were treated for diffuse large B cell lymphoma (DLBCL), one with bsAb and the other with CAR T cell. Fifty percent (3/6) of DLBCL patients who received an anti-IL6/IL6R presented an infection, one of which was a grade 5. In solid tumor patients treated with bsAb and anti-IL6/IL6R, only one patient (/9, 11%) developed a grade 2 viral infection. CONCLUSION: It seems that the use of anti-IL6/IL6R in CRS secondary to bsAb administration in solid tumors patients does not significantly increase the risk of infection, as opposed to DLBCL patients where secondary infection might be a concern.

Effect of continuous positive airway pressure in very elderly with moderate-to-severe obstructive sleep apnea pooled results from two multicenter randomized controlled trials.

STUDY OBJECTIVE: There is very limited information about the effect of continuous positive airway pressure (CPAP) in the very elderly. Here we aimed to analysed the effect of CPAP on a clinical cohort of patients with obstructive sleep apnea (OSA) ≥80 years old. METHODS: Post-hoc pooled analysis of two open-label, multicenter clinical trials aimed to determine the effect of CPAP in a consecutive clinical cohort of elderly (≥70 years old) with moderate-to-severe OSA (apnea-hipopnea index ≥15 events/hour) randomized to receive CPAP or no CPAP for three months. Those consecutive patients ≥80 years old were included in the study. The primary endpoint was the change in Epworth Sleepiness scale (ESS). Secondary outcomes included sleep-related symptoms, quality of life, neurocognitive and mood status as well as office blood pressure measurements. RESULTS: From the initial 369 randomized individuals with ≥70 years, 97 (26.3%) with ≥80 years old were included (47 in the CPAP group and 50 in the no-CPAP group). The mean (SD) age was 81.5 (2.4) years. Average use of CPAP was 4.3 (2.6) hours/night (53% with good adherence) Patients in the CPAP group significantly improved snoring and witnessed apneas as well as AHI (from 41.9 to 4.9 events/hour). However no clinical improvements were seen in ESS (-1.2 points, 95%CI, 0.2 to -2.6), any domain of QSQ, any neurocognitive test, OSA-related symptoms, depression/anxiety or blood pressure levels. CONCLUSIONS: The present study does not support the use of CPAP in very elderly patients with moderate-to-severe OSA.

Bimodality and the genetics of milk flow traits in the Italian Holstein-Friesian breed.

The overall goal of this study was to investigate milk flow traits in Italian Holstein-Friesian cows and, in particular, the bimodality of milk flow, defined as delayed milk ejection at the start of milking. Using a milkometer, 2,886 records were collected from 133 herds in northern Italy from 2001 to 2007. All records included 5 time-period measurements for milk flow, somatic cell score (SCS), milk yield, 8 udder type traits, and the presence or absence of bimodality in milk flow. Genetic parameters were estimated using linear animal models for continuous traits such as milk flow, udder type, SCS, and milk production, whereas bimodality was analyzed as a categorical trait. With the exception of decreasing time (which had a very small heritability value of 0.06), heritability values for milk flow traits were moderate, ranging from 0.10 (ascending time) to 0.41 (maximum milk flow). In addition, moderate to high genetic correlations were estimated between total milking time and other time measures (from 0.78 to 0.87), and among time flow traits (from 0.62 to 0.91). The decreasing time was the trait most genetically correlated with udder type traits, with correlation values of 0.92 with rear udder height, 0.85 with rear udder width, and 0.73 with teat placement. Large udders with strong attachments were also associated with greater milk production. Heritability estimated for bimodality was 0.43, and its genetic correlation with milk flow traits and SCS indicated a sizable genetic component underlying this trait. Bimodality was negatively associated with milk production; shorter milking times and greater peak milk levels were genetically correlated with more frequent bimodal flows, indicating that faster milk release would result in an increase in bimodal patterns. The negative genetic correlation of bimodality with SCS (-0.30) and the genetic correlation between milk flow traits and SCS suggest that the relationship between milkability and SCS is probably nonlinear and that intermediate flow rates are optimal with respect to mastitis susceptibility. Quicker milk flow over a shorter period would increase the frequency of bimodal curves in milking, whereas the correlation between bimodality and both ascending and descending time was less clear.

Predictive Model for Allergic Contact Dermatitis in Patients With Hand Eczema. / Modelo predictivo de dermatitis alérgica de contacto en pacientes con eccema de manos.

INTRODUCTION: Patch tests are only indicated for hand eczema when it is diagnosed as chronic. A positive reaction of current relevance requires a change in treatment strategy. Knowing which clinical factors are associated with current relevance would allow tests to be performed sooner. OBJECTIVE: To develop a model for predicting currently relevant patch test positivity in patients with hand eczema only. MATERIAL AND METHODS: Retrospective study of patients with hand eczema only. We collected data on age, sex, time since onset, occupation, and history of atopic dermatitis. We built a predictive logistic regression model and assessed discrimination by computing the area under the receiver operating characteristic curve. RESULTS: We included 262 patients; 66.03% had positive patch tests (28.6% of current relevance). Univariate analysis detected significant associations between positivity of current relevance and employment as a hairdresser-aesthetician, a personal history of atopy, male sex, and a time since onset of over 6 months. Multivariate analysis confirmed employment as a hairdresser-aesthetician as an independent risk factor and male sex and a personal history of atopy as protective factors. The score suggested by the predictive model was 2.316(hairdresser-aesthetician)-1.792(atopic dermatitis)-0.601(male sex). CONCLUSIONS: Occupation, sex, and a history of atopy influence the likelihood of patch test positivity of current relevance in patients with hand eczema in Spain. Our model suggests that a diagnosis of chronic eczema is not necessarily an indication for patch testing. Future studies with larger samples are needed to determine the true usefulness of predictive models in this setting.

SEOM clinical guidelines for the treatment of small-cell lung cancer (SCLC) (2019).

Small-cell lung cancer (SCLC) accounts for 15% of lung cancers. Only one-third of patients are diagnosed at limited stage. The median survival remains to be around 15-20 months without significative changes in the strategies of treatment for many years. In stage I and IIA, the standard treatment is the surgery followed by adjuvant therapy with platinum-etoposide. In stage IIB-IIIC, the recommended treatment is early concurrent chemotherapy with platinum-etoposide plus thoracic radiotherapy followed by prophylactic cranial irradiation in patients without progression. However, in the extensive stage, significant advances have been observed adding immunotherapy to platinum-etoposide chemotherapy to obtain a significant increase in overall survival, constituting the new recommended standard of care. In the second-line treatment, topotecan remains as the standard treatment. Reinduction with platinum-etoposide is the recommended regimen in patients with sensitive relapse (≥ 3 months) and new drugs such as lurbinectedin and immunotherapy are new treatment options. New biomarkers and new clinical trials designed according to the new classification of SCLC subtypes defined by distinct gene expression profiles are necessary.

Malignant pleural mesothelioma: Treatment patterns and outcomes from the Spanish Lung Cancer Group.

BACKGROUND: Malignant mesothelioma is a rare but aggressive tumor arising from the pleura, typically associated with exposure to asbestos. The purpose of this investigation was to describe mesothelioma patient characteristics, treatment patterns, and outcomes in Spain. MATERIAL AND METHODS: Patients diagnosed with malignant mesothelioma of the pleura were recorded in an anonymous online database (BEMME, Epidemiologic Spanish Malignant Mesothelioma Database) from June 2008 through May 2013. Patient and tumor characteristics at time of diagnosis, as well as subsequent treatments (surgery, radiation, and chemotherapy), were collected. Among patients treated with chemotherapy, we explored type of chemotherapy regimen and outcomes by treatments. RESULTS: A total of 560 malignant pleural mesothelioma (MPM) patients were recorded. The median age at diagnosis was 68 years, mainly with epithelioid histology (62 %), and any asbestos exposure was noted in 45 % of patients. Nearly two-thirds of patients (71 %) received chemotherapy, mainly platinum-pemetrexed combination, as part of their treatment. Surgery and radiotherapy were given in 36 % and 17 % of patients, respectively. The median overall survival (OS) in the whole cohort was 13.0 months (95 % confidence interval (CI), 11.1-14.8 months) with 1-year OS of 53.2 % (95 % CI, 48.7-57.7 %). In patients receiving first-line chemotherapy (N = 315), the median OS was 13.4 months (95 % CI, 10.8-16.0 months), reaching 20.2 months (95 % CI, 17.2-23.2 months) for those 68 patients receiving maintenance chemotherapy. Results of multivariate analyses showed significant association of ECOG-performance status, histology and treatment response with improved OS in MPM patients treated with palliative chemotherapy. CONCLUSIONS: Despite multimodal therapeutic intervention, survival of patients with mesothelioma in Spain remains poor. Although it did not reach significance in the multivariate analysis, a meaningful additional survival benefit was observed among those patients receiving maintenance chemotherapy.

Behaviors, Attitudes, and Knowledge Related to Sun Exposure Among Medical Students at the Universidad de Las Palmas de Gran Canaria. / Comportamientos, actitudes y conocimientos relacionados con la exposición solar en estudiantes de medicina de la Universidad de Las Palmas de Gran Canaria.

INTRODUCTION: The incidence of skin cancer, for which the main risk factor is exposure to ultraviolet radiation, has risen worldwide. Sunburn is one of the simplest ways to assess sun exposure habits. To date, few studies have evaluated sun exposure in university students. OBJECTIVES: To determine behaviors, attitudes, and knowledge related to sun exposure and sun protection measures among medical students at the Universidad de Las Palmas de Gran Canaria; and to assess their relation to sunburn frequency. MATERIAL AND METHODS: The voluntary participants in this cross-sectional survey were first-, second- and sixth-year university students enrolled during the 2016-2017 academic year. The students responded to a validated questionnaire about their habits, attitudes, and knowledge in relation to sun exposure. Respondents were grouped according to the number of sunburns they had experienced during the previous summer. RESULTS: A total of 286 students responded. The students demonstrated a high level of knowledge, but the percentage who experienced a sunburn was high. Multivariate analysis showed independent correlations between experiencing a sunburn and age, male sex, academic year of enrollment at the time of the survey, phototype, and negative attitudes toward the use of sun protection measures. CONCLUSIONS: Our medical students' level of knowledge about sun exposure and sun protection is high and scarcely varies with time spent at the university. However, their knowledge is not reflected in their behavior and attitudes or in the frequency of sunburns.

Genome-Wide Association Studies for Methane Production in Dairy Cattle.

Genomic selection has been proposed for the mitigation of methane (CH4) emissions by cattle because there is considerable variability in CH4 emissions between individuals fed on the same diet. The genome-wide association study (GWAS) represents an important tool for the detection of candidate genes, haplotypes or single nucleotide polymorphisms (SNP) markers related to characteristics of economic interest. The present study included information for 280 cows in three dairy production systems in Mexico: 1) Dual Purpose (n = 100), 2) Specialized Tropical Dairy (n = 76), 3) Familiar Production System (n = 104). Concentrations of CH4 in a breath of individual cows at the time of milking (MEIm) were estimated through a system of infrared sensors. After quality control analyses, 21,958 SNPs were included. Associations of markers were made using a linear regression model, corrected with principal component analyses. In total, 46 SNPs were identified as significant for CH4 production. Several SNPs associated with CH4 production were found at regions previously described for quantitative trait loci of composition characteristics of meat, milk fatty acids and characteristics related to feed intake. It was concluded that the SNPs identified could be used in genomic selection programs in developing countries and combined with other datasets for global selection.

The associations between anthropometric measurements and left ventricular structure and function: the Echo-SOL Study.

OBJECTIVE: The objective of this study is to determine associations between anthropometry and echocardiographic measures of cardiac structure and function in Hispanic/Latinos. METHODS: A total of 1,824 participants from ECHO-SOL were included. We evaluated associations between echocardiographic measures of left ventricular structure and function and anthropometric measures using multivariable-adjusted linear and logistic regression models adjusting for traditional cardiovascular risk factors. RESULTS: The mean age was 56 ± 0.17 years, 57% were women. The mean body mass index (BMI) was 30 ± 9.4 kg m-2, waist circumference (WC) was 100 ± 18 cm, and waist-to-hip ratio (WHR) was 0.93 ± 0.15. Adjusted analysis showed that 5-unit increment in BMI and 5-cm increase in WC was associated with 3.4 ± 0.6 and 1.05 ± 0.05 g m-2.7 (p < 0.05 for both) higher left ventricular (LV) mass index, respectively. Similarly, 0.1-unit increment in WHR was associated with 2.0 ± 0.16 g m-2.7 higher LV mass index (p < 0.01). WHR was associated with 0.22 ± 0.08% decrease in ejection fraction (p < 0.05). Concomitantly, 5-unit increment in BMI and WC was associated with increased odds of abnormal LV geometry (odds ratio 1.40 and 1.16, p = 0.03 and <0.01, respectively); 0.1-unit increment in WHR was associated with increased odds of abnormal LV geometry (odds ratio 1.51, p < 0.01). CONCLUSIONS: Among Hispanic/Latinos, higher anthropometric measures were associated with adverse cardiac structure and function.