High-density single-nucleotide polymorphism maps of the human genome

Miller, Raymond D.,Phillips, Michael S.,Jo, Inho,Donaldson, Miriam A.,Studebaker, Joel F.,Addleman, Nicholas,Alfisi, Steven V.,Ankener, Wendy M.,Bhatti, Hamid A.,Callahan, Chad E.,Carey, Benjamin J.,C Elsevier 2005 Genomics Vol.86 No.2

<P><B>Abstract</B></P><P>Here we report a large, extensively characterized set of single-nucleotide polymorphisms (SNPs) covering the human genome. We determined the allele frequencies of 55,018 SNPs in African Americans, Asians (Japanese–Chinese), and European Americans as part of The SNP Consortium's Allele Frequency Project. A subset of 8333 SNPs was also characterized in Koreans. Because these SNPs were ascertained in the same way, the data set is particularly useful for modeling. Our results document that much genetic variation is shared among populations. For autosomes, some 44% of these SNPs have a minor allele frequency ≥10% in each population, and the average allele frequency differences between populations with different continental origins are less than 19%. However, the several percentage point allele frequency differences among the closely related Korean, Japanese, and Chinese populations suggest caution in using mixtures of well-established populations for case–control genetic studies of complex traits. We estimate that ∼7% of these SNPs are private SNPs with minor allele frequencies <1%. A useful set of characterized SNPs with large allele frequency differences between populations (>60%) can be used for admixture studies. High-density maps of high-quality, characterized SNPs produced by this project are freely available.</P>

Preoperative Body Mass Index, 30-Day Postoperative Morbidity, Length of Stay and Quality of Life in Patients Undergoing Pelvic Exenteration Surgery for Recurrent and Locally-Advanced Rectal Cancer

Jessica Beaton,,Sharon Carey,Michael J Solomon,Ker-Kan Tan,Jane Young 대한대장항문학회 2014 Annals of Coloproctolgy Vol.30 No.2

Purpose: Malnutrition is associated with an increased risk of developing complications following gastrointestinal surgery, especially following radical surgeries such as pelvic exenteration. This study aims to determine if preoperative body mass index (BMI) is associated with 30-day morbidity, length of hospital stay and/or quality of life (QoL) in patients undergoing pelvic exenteration surgery for recurrent and locally-advanced rectal cancer prior to a prospective trial. Methods: A review of all patients who underwent pelvic exenteration surgery prior to 2008 was performed. Patients were included if they had a documented BMI as well as a QoL measurement (Functional Assessment Cancer Therapy - Colorectal questionnaire). Results: Thirty-one patients, with a mean age of 56 years, had preoperative height and weight data, as well as measures of postoperative QoL, and formed the study group. The numbers of patients with recurrent (n = 17) or locally-advanced rectal cancer (n = 14) were similar. The mean length of stay was 21 days while the mean BMI of the patients was 24.3 (± 5.9) kg/m2. The majority of the patients were either of normal weight (n = 15) or overweight/obese (n = 11). The average length of hospital stay was significantly longer in patients who were underweight compared to those who were of normal weight (F = 6.508, P = 0.006) and those who were overweight and obese (F = 6.508, P = 0.007). Conclusion: This study suggests that a lower body mass index preoperatively is associated with a longer length of hospital stay. BMI is not associated with long-term QoL in this patient group. However, further prospective research is required.

Features of Recently Transmitted HIV-1 Clade C Viruses that Impact Antibody Recognition: Implications for Active and Passive Immunization

Rademeyer, Cecilia,Korber, Bette,Seaman, Michael S.,Giorgi, Elena E.,Thebus, Ruwayhida,Robles, Alexander,Sheward, Daniel J.,Wagh, Kshitij,Garrity, Jetta,Carey, Brittany R.,Gao, Hongmei,Greene, Kelli M Public Library of Science 2016 PLoS pathogens Vol.12 No.7

<▼1><P>The development of biomedical interventions to reduce acquisition of HIV-1 infection remains a global priority, however their potential effectiveness is challenged by very high HIV-1 envelope diversity. Two large prophylactic trials in high incidence, clade C epidemic regions in southern Africa are imminent; passive administration of the monoclonal antibody VRC01, and active immunization with a clade C modified RV144-like vaccines. We have created a large representative panel of C clade viruses to enable assessment of antibody responses to vaccines and natural infection in Southern Africa, and we investigated the genotypic and neutralization properties of recently transmitted clade C viruses to determine how viral diversity impacted antibody recognition. We further explore the implications of these findings for the potential effectiveness of these trials. A panel of 200 HIV-1 Envelope pseudoviruses was constructed from clade C viruses collected within the first 100 days following infection. Viruses collected pre-seroconversion were significantly more resistant to serum neutralization compared to post-seroconversion viruses (p = 0.001). Over 13 years of the study as the epidemic matured, HIV-1 diversified (p = 0.0009) and became more neutralization resistant to monoclonal antibodies VRC01, PG9 and 4E10. When tested at therapeutic levels (10ug/ml), VRC01 only neutralized 80% of viruses in the panel, although it did exhibit potent neutralization activity against sensitive viruses (IC<SUB>50</SUB> titres of 0.42 μg/ml). The Gp120 amino acid similarity between the clade C panel and candidate C-clade vaccine protein boosts (Ce1086 and TV1) was 77%, which is 8% more distant than between CRF01_AE viruses and the RV144 CRF01_AE immunogen. Furthermore, two vaccine signature sites, K169 in V2 and I307 in V3, associated with reduced infection risk in RV144, occurred less frequently in clade C panel viruses than in CRF01_AE viruses from Thailand. Increased resistance of pre-seroconversion viruses and evidence of antigenic drift highlights the value of using panels of very recently transmitted viruses and suggests that interventions may need to be modified over time to track the changing epidemic. Furthermore, high divergence such as that observed in the older clade C epidemic in southern Africa may impact vaccine efficacy, although the correlates of infection risk are yet to be defined in the clade C setting. Findings from this study of acute/early clade C viruses will aid vaccine development, and enable identification of new broad and potent antibodies to combat the HIV-1 C-clade epidemic in southern Africa.</P></▼1><▼2><P><B>Author Summary</B></P><P>Vaccine and passive immunization prophylactic trials that rely on antibody-mediated protection are planned for HIV-1 clade C epidemic regions of southern Africa, which have amongst the highest HIV-1 incidences globally. This includes a phase 2b trial of passively administered monoclonal antibody, VRC01; as well as a phase 3 trial using the clade C modified version of the partially efficacious RV144 vaccine. The extraordinary diversity of HIV-1 poses a major obstacle to these interventions, and our study aimed to determine the implications of viral diversity on antibody recognition. Investigations using our panel of very early viruses augment current knowledge of vulnerable targets on transmitted viruses for vaccine design and passive immunization studies. Evidence of antigenic drift with viruses becoming more resistant over time suggests that these prevention modalities will need to be updated over time and that combinations of antibodies will be necessary to achieve coverage in passive immunization studies. We further show that it may be more difficult to obtain protection in the genetically diverse clade C epidemic compared to RV144 where the epidemic is less diverse, although it should be noted that the correlates of infection risk are yet to be defined in the clade C setti

Sarcopenia and Post-Operative Morbidity and Mortality in Patients with Gastric Cancer

O'Brien, Stephen,Twomey, Maria,Moloney, Fiachra,Kavanagh, Richard G.,Carey, Brian W.,Power, Derek,Maher, Michael M.,O'Connor, Owen J.,O'Suilleabhain, Criostoir The Korean Gastric Cancer Association 2018 Journal of gastric cancer Vol.18 No.3

Purpose: Surgical resection for gastric adenocarcinoma is associated with significant post-operative morbidity and mortality. The aim of this study was to assess the prognostic significance of sarcopenia in patients undergoing resection for gastric adenocarcinoma with respect to post-operative morbidity and survival. Materials and Methods: A retrospective analysis was conducted on a cohort of consecutive patients who underwent surgical resection for gastric adenocarcinoma between 2008 and 2014. Patient demographics, radiological parameters, and pathological data were collected. OsiriX software (Pixmeo) was used to measure skeletal muscle area, which was normalized for height to calculate skeletal muscle index. Results: A total of 56 patients (41 male, 15 female; mean age, $68.4{\pm}11.9years$) met the inclusion criteria. Of these, 36% (20 of 56) of the patients were sarcopenic pre-operatively. Both sarcopenic and non-sarcopenic patient groups were equally matched with the exception of weight and body mass index (P=0.036 and 0.001, respectively). Sarcopenia was associated with a decreased overall survival (log-rank P=0.003) and was an adverse prognostic predictor of overall survival in multivariate analysis (hazard ratio, 10.915; P=0.001). Sarcopenia was a predictor of serious in-hospital complications in multivariate analysis (odds ratio, 3.508; P=0.042). Conclusions: In patients undergoing curative resection for gastric cancer, there was a statistically significant association between sarcopenia and both decreased overall survival and serious post-operative complications. The measurement and reporting of skeletal muscle index on pre-operative computed tomography should be considered.

Sarcopenia and Post-Operative Morbidity and Mortality in Patients with Gastric Cancer

Stephen O Brien,Maria Twomey,Fiachra Moloney,Richard G. Kavanagh,Brian W. Carey,Derek Power,Michael M. Maher,Owen J. OConnor,Criostoir ÓSúilleabháin 대한위암학회 2018 Journal of gastric cancer Vol.18 No.3

Purpose: Surgical resection for gastric adenocarcinoma is associated with significant post-operative morbidity and mortality. The aim of this study was to assess the prognostic significance of sarcopenia in patients undergoing resection for gastric adenocarcinoma with respect to post-operative morbidity and survival. Materials and Methods: A retrospective analysis was conducted on a cohort of consecutive patients who underwent surgical resection for gastric adenocarcinoma between 2008 and 2014. Patient demographics, radiological parameters, and pathological data were collected. OsiriX software (Pixmeo) was used to measure skeletal muscle area, which was normalized for height to calculate skeletal muscle index. Results: A total of 56 patients (41 male, 15 female; mean age, 68.4 ± 11.9 years) met the inclusion criteria. Of these, 36% (20 of 56) of the patients were sarcopenic pre-operatively. Both sarcopenic and non-sarcopenic patient groups were equally matched with the exception of weight and body mass index (P=0.036 and 0.001, respectively). Sarcopenia was associated with a decreased overall survival (log-rank P=0.003) and was an adverse prognostic predictor of overall survival in multivariate analysis (hazard ratio, 10.915; P=0.001). Sarcopenia was a predictor of serious in-hospital complications in multivariate analysis (odds ratio, 3.508; P=0.042). Conclusions: In patients undergoing curative resection for gastric cancer, there was a statistically significant association between sarcopenia and both decreased overall survival and serious post-operative complications. The measurement and reporting of skeletal muscle index on pre-operative computed tomography should be considered.