Intravenous Fluid Technique in Infancy

A CAJM article on medically administering Intravenous Fluids to infants in the then Southern Rhodesia.Outside the children’s hospital, the administration of intravenous fluids in babies is fortunately an unusual necessity. Rightly, subcutaneous fluids given with hyalase are used extensively in the milder cases of dehydration and are usually sufficient to correct the imbalance. However, in infants severely dehydrated from, for example, gastroenteritis or pyloric stenosis, in those with peripheral vascular failure from overwhelming toxaemia, in cases of severe haemorrhage and in burns and other surgical problems, the need for an intravenous '‘drip” arises, often with great urgency. Generally a “cut-down” will be performed over the ankle, often after several time-consuming but unsuccessful attempts at “push-ins” in arm, wrist or scalp. As like as not, the “cut-down” drip, when completed, will be found to be delivering only a niggardly five drops per minute, despite the injection of a local anaesthetic to relax venous spasm and with the infant's condition steadily deteriorating. This communication will draw attention to some principles and techniques which have been found successful in dealing with problems of this sort

Analysis of amniotic fluid in the management of the Rhesus-sensitized pregnancy

No Abstract

Book Reviews

Book 1 Book Title: Basic EpidemiologyBook Authors: R. Beaglehole, R. Bonita & T. KjellströmPp. viii + 174. (in English, French and Spanish in preparation). $19,40. Geneva: WHO. 1993. Order No. 1150395. ISBN 92-4-154446-5.Book 2Book Title: A Pocket Book of Social and Community PaediatricsBook Author: Jo SibertPp. viii + 164. London: Edward Arnold. 1992. ISBN 0-340-54929-7.Book 3Book Title: Knowledge Beats CancerBook Author: Albert Stegmann AlbertsPp. 226. Illustrated. R55,45. Pretoria: Haum Tertiary. 1993. ISBN 0-7986-3196-1.Book 4Book Title: AIDS and Your ResponsePp. vi + 226. R49,50. ISBN 0-620-17319-X.Book 5Book Title: Principles for Evaluating Chemical Effects on the Aged Population. Enviromnental Health Criteria. No. 144Book Author: W.H.O.Pp. 159. (English only).$20,50. Geneva: WHO. 1993. Order No. 1160144. ISBN 92-4-1571446.Book 6Book Title: The Guide to Heart Sounds: Normal and AbnormalBook Authors: Donald W. Novey, Marcia Pencak & John M. StangAudio-cassette narrated by: Donald W. Novey. pp. xi + 74. Illustrated. Florida: CRC Press. 1988. ISB J 0-8493-0153X.Book 7Book Title: Propachlor. Enviromnental Health Criteria. No. 147Book Author: W.H.O.Pp. 110. (English, French and Spanish summaries). $17,30. Geneva: WHO. 1993. Order TO. 1160147. ISBN 92-4-157147-0.Book 8Book Title: Quality Assurance in Health Care: A HandbookBook Authors: Roger Ellis & Dorothy WhittingronLondon: Edward Arnold. 1993. ISBN 0-340-55273-5.Book 9Book Title:  Rehabilitation after Cardiovascular Diseases, with Special Emphasis on Developing CountriesReport of a WHO expert committee. Technical Report Series No 831. Pp. viii + 122 (available in English, French and Spanish in preparation). Geneva: WHO. 1993. ISBN 92-4-120831-7

Books

Oral cancer Oral Cancer: Epidemiology, Etiology and Pathology. Ed. by Colin Smith, Jens Pindborg and W. H. Binnie. Pp. ix + 106. Illustrated. R183,30. USA: Hemisphere. 1990.HPV and cervical cancer Human Papillomavirus and Cervical Cancer. Ed. by N. Munoz, F. X. Bosch and O. M. Jensen. Pp. xii + 155. Illustrated. France: International Agency for Research on Cancer. 1989.Child health Child Health in a Multicultural Society. Ed. by John Black. Pp. 75. Illustrated. £7 (including postage). London: BMJ. 1989. (Available also from Libriger Book Distributors).Merck manual of geriatics Merck Manual of Geriatrics. Ed. by William B. Abrams The Andrew J. Fletcher. Pp. xxii + 1267. Illustrated. RI4,50. and I: Merck. 1990. USALiver disease Progress in Liver Diseases. Vol 9. Ed. by Hans Popper and Fenton Schaffner. Pp. xv + 750. Illustrated. RllO. England: Harcourt Brace Jovanovich. 1990.Clinical dietetics and nutrition Clinical Dietetics and Nutrition. 3rd ed. Ed. by F. P. Antia. Pp. xvi +438. Illustrated. Oxford: Oxford University Press. 1989.Atlas of human anatomy Wolf-Heidegger's Atlas of Human Anatomy. Ed. by H. F. Frick, B. Kummer and R. V. Putz. pp. viii + 599. £(j(J. Basel: Karger. 1990.Health system decentralisation Health System Decentralization. Ed. by A. Mills, J. P. Vaughan, D. L. Smith and I. Tabibzadcll. pp. 151. Illustrated. SFr. 26. Geneva: World Health Organisation. 1990.Handbook of occupational medicine Handbook of Occupational Medicine. Ed. by Robert J. McCunney. Pp. xxiii + 510. Illustrated. Boston: Little, Brown. 1988.Leukaemia Leukaemia. 5th ed. Ed. by Edward S. Henderson and T. Andrew Lister. Pp. vii + 821. Illustrated. RHO. Kent: Harcoun Brace Jovanovich. 1990

An Integrated TCGA Pan-Cancer Clinical Data Resource to Drive High-Quality Survival Outcome Analytics

For a decade, The Cancer Genome Atlas (TCGA) program collected clinicopathologic annotation data along with multi-platform molecular profiles of more than 11,000 human tumors across 33 different cancer types. TCGA clinical data contain key features representing the democratized nature of the data collection process. To ensure proper use of this large clinical dataset associated with genomic features, we developed a standardized dataset named the TCGA Pan-Cancer Clinical Data Resource (TCGA-CDR), which includes four major clinical outcome endpoints. In addition to detailing major challenges and statistical limitations encountered during the effort of integrating the acquired clinical data, we present a summary that includes endpoint usage recommendations for each cancer type. These TCGA-CDR findings appear to be consistent with cancer genomics studies independent of the TCGA effort and provide opportunities for investigating cancer biology using clinical correlates at an unprecedented scale. Analysis of clinicopathologic annotations for over 11,000 cancer patients in the TCGA program leads to the generation of TCGA Clinical Data Resource, which provides recommendations of clinical outcome endpoint usage for 33 cancer types

Driver Fusions and Their Implications in the Development and Treatment of Human Cancers.

Gene fusions represent an important class of somatic alterations in cancer. We systematically investigated fusions in 9,624 tumors across 33 cancer types using multiple fusion calling tools. We identified a total of 25,664 fusions, with a 63% validation rate. Integration of gene expression, copy number, and fusion annotation data revealed that fusions involving oncogenes tend to exhibit increased expression, whereas fusions involving tumor suppressors have the opposite effect. For fusions involving kinases, we found 1,275 with an intact kinase domain, the proportion of which varied significantly across cancer types. Our study suggests that fusions drive the development of 16.5% of cancer cases and function as the sole driver in more than 1% of them. Finally, we identified druggable fusions involving genes such as TMPRSS2, RET, FGFR3, ALK, and ESR1 in 6.0% of cases, and we predicted immunogenic peptides, suggesting that fusions may provide leads for targeted drug and immune therapy

Fine-mapping of prostate cancer susceptibility loci in a large meta-analysis identifies candidate causal variants

Prostate cancer is a polygenic disease with a large heritable component. A number of common, low-penetrance prostate cancer risk loci have been identified through GWAS. Here we apply the Bayesian multivariate variable selection algorithm JAM to fine-map 84 prostate cancer susceptibility loci, using summary data from a large European ancestry meta-analysis. We observe evidence for multiple independent signals at 12 regions and 99 risk signals overall. Only 15 original GWAS tag SNPs remain among the catalogue of candidate variants identified; the remainder are replaced by more likely candidates. Biological annotation of our credible set of variants indicates significant enrichment within promoter and enhancer elements, and transcription factor-binding sites, including AR, ERG and FOXA1. In 40 regions at least one variant is colocalised with an eQTL in prostate cancer tissue. The refined set of candidate variants substantially increase the proportion of familial relative risk explained by these known susceptibility regions, which highlights the importance of fine-mapping studies and has implications for clinical risk profiling. © 2018 The Author(s).Prostate cancer is a polygenic disease with a large heritable component. A number of common, low-penetrance prostate cancer risk loci have been identified through GWAS. Here we apply the Bayesian multivariate variable selection algorithm JAM to fine-map 84 prostate cancer susceptibility loci, using summary data from a large European ancestry meta-analysis. We observe evidence for multiple independent signals at 12 regions and 99 risk signals overall. Only 15 original GWAS tag SNPs remain among the catalogue of candidate variants identified; the remainder are replaced by more likely candidates. Biological annotation of our credible set of variants indicates significant enrichment within promoter and enhancer elements, and transcription factor-binding sites, including AR, ERG and FOXA1. In 40 regions at least one variant is colocalised with an eQTL in prostate cancer tissue. The refined set of candidate variants substantially increase the proportion of familial relative risk explained by these known susceptibility regions, which highlights the importance of fine-mapping studies and has implications for clinical risk profiling. © 2018 The Author(s).Peer reviewe

Perspective on Oncogenic Processes at the End of the Beginning of Cancer Genomics

The Cancer Genome Atlas (TCGA) has catalyzed systematic characterization of diverse genomic alterations underlying human cancers. At this historic junction marking the completion of genomic characterization of over 11,000 tumors from 33 cancer types, we present our current understanding of the molecular processes governing oncogenesis. We illustrate our insights into cancer through synthesis of the findings of the TCGA PanCancer Atlas project on three facets of oncogenesis: (1) somatic driver mutations, germline pathogenic variants, and their interactions in the tumor; (2) the influence of the tumor genome and epigenome on transcriptome and proteome; and (3) the relationship between tumor and the microenvironment, including implications for drugs targeting driver events and immunotherapies. These results will anchor future characterization of rare and common tumor types, primary and relapsed tumors, and cancers across ancestry groups and will guide the deployment of clinical genomic sequencing

Pathogenic Germline Variants in 10,389 Adult Cancers

We conducted the largest investigation of predisposition variants in cancer to date, discovering 853 pathogenic or likely pathogenic variants in 8% of 10,389 cases from 33 cancer types. Twenty-one genes showed single or cross-cancer associations, including novel associations of SDHA in melanoma and PALB2 in stomach adenocarcinoma. The 659 predisposition variants and 18 additional large deletions in tumor suppressors, including ATM, BRCA1, and NF1, showed low gene expression and frequent (43%) loss of heterozygosity or biallelic two-hit events. We also discovered 33 such variants in oncogenes, including missenses in MET, RET, and PTPN11 associated with high gene expression. We nominated 47 additional predisposition variants from prioritized VUSs supported by multiple evidences involving case-control frequency, loss of heterozygosity, expression effect, and co-localization with mutations and modified residues. Our integrative approach links rare predisposition variants to functional consequences, informing future guidelines of variant classification and germline genetic testing in cancer. A pan-cancer analysis identifies hundreds of predisposing germline variants