Developing a partnership to improve health care delivery to children <18 years with cancer and blood disorders in the English-speaking Caribbean: lessons from the SickKids-Caribbean Initiative (SCI).

In 2013, the SickKids-Caribbean Initiative (SCI) was formalised among The Hospital for Sick Children in Toronto, Canada, the University of the West Indies, and Ministries of Health in six Caribbean countries (Barbados, The Bahamas, Jamaica, St. Lucia, St. Vincent and the Grenadines, and Trinidad and Tobago). The aim was to improve the outcomes and quality of life of children (<18 years) with cancer and blood disorders in the partner countries. Core activities included filling a human resource gap by training paediatric haematologists/oncologists and specialised registered nurses; improving capacity to diagnose and treat diverse haematology/oncology cases; developing and maintaining paediatric oncology databases; creating ongoing advocacy activities with international agencies, decision makers, and civil society; and establishing an integrated administration, management, and funding structure. We describe core program components, successes, and challenges to inform others seeking to improve health service delivery in a multidisciplinary and complex partnership.

Heterogeneity in head and neck cancer incidence among black populations from Africa, the Caribbean and the USA: Analysis of cancer registry data by the AC3.

BACKGROUND: Africa and the Caribbean are projected to have greater increases in Head and neck cancer (HNC) burden in comparison to North America and Europe. The knowledge needed to reinforce prevention in these populations is limited. We compared for the first time, incidence rates of HNC in black populations from African, the Caribbean and USA. METHODS: Annual age-standardized incidence rates (IR) and 95% confidence intervals (95%CI) per 100,000 were calculated for 2013-2015 using population-based cancer registry data for 14,911 HNC cases from the Caribbean (Barbados, Guadeloupe, Trinidad & Tobago, N = 443), Africa (Kenya, Nigeria, N = 772) and the United States (SEER, Florida, N = 13,696). We compared rates by sub-sites and sex among countries using data from registries with high quality and completeness. RESULTS: In 2013-2015, compared to other countries, HNC incidence was highest among SEER states (IR: 18.2, 95%CI = 17.6-18.8) among men, and highest in Kenya (IR: 7.5, 95%CI = 6.3-8.7) among women. Nasopharyngeal cancer IR was higher in Kenya for men (IR: 3.1, 95%CI = 2.5-3.7) and women (IR: 1.5, 95%CI = 1.0-1.9). Female oral cavity cancer was also notably higher in Kenya (IR = 3.9, 95%CI = 3.0-4.9). Blacks from SEER states had higher incidence of laryngeal cancer (IR: 5.5, 95%CI = 5.2-5.8) compared to other countries and even Florida blacks (IR: 4.4, 95%CI = 3.9-5.0). CONCLUSION: We found heterogeneity in IRs for HNC among these diverse black populations; notably, Kenya which had distinctively higher incidence of nasopharyngeal and female oral cavity cancer. Targeted etiological investigations are warranted considering the low consumption of tobacco and alcohol among Kenyan women. Overall, our findings suggest that behavioral and environmental factors are more important determinants of HNC than race.

Breast Cancer in Jamaica: Trends From 2010 to 2014-Is Mortality Increasing?

PURPOSE: This study sought to provide a detailed analysis of breast cancer-specific mortality in Jamaica on the basis of reported deaths between 2010 and 2014. METHODS: A cross-sectional study was done to analyze breast cancer-specific mortality data from the Registrar General's Department, the statutory body responsible for registering all deaths across Jamaica. RESULTS: A total of 1,634 breast cancer-related deaths were documented among Jamaican women between 2010 and 2014, which accounted for 24% of all female cancer deaths. The age-standardized breast cancer mortality rate increased from 21.8 per 100,000 in 2010 to 28 per 100,000 in 2014 for the total female population. The overall difference in breast cancer mortality rates between the 2014 and 2010 rates was not statistically significant (P = .114). Analysis of the year-by-year trend reflected by the annual percentage of change did show, however, a statistically significant increasing trend in breast cancer mortality (P = .028). Mortality rates varied by age, with statistically significant annual increases observed in the 35-44-, 65-74-, and ≥ 75-year age groups (P = .04, .03, and .01, respectively). CONCLUSION: Breast cancer remains the leading cause of death among Jamaican women. Despite global advances in breast cancer screening and management, breast cancer remains a major public health challenge and represents a public health priority in Jamaica. The increasing breast cancer-specific mortality in Jamaica over the 5-year period contrasts with decreasing mortality rates among US women with breast cancer. This study highlights the critical need to address the implementation of a national organized breast cancer screening program in Jamaica and to focus future research efforts on the biology of breast cancer, especially among young Jamaican women.

Advancing cancer care and prevention in the Caribbean: a survey of strategies for the region.

Cancer is now the second leading cause of death in the Caribbean. Despite this growing burden, many Caribbean small island nations have health systems that struggle to provide optimal cancer care for their populations. In this Series paper, we identify several promising strategies to improve cancer prevention and treatment that have emerged across small island nations that are part of the Caribbean Community. These strategies include the establishment of a Caribbean cancer registry hub, the development of resource-appropriate clinical guidelines, innovations in delivering specialty oncology services (eg, paediatric oncology and palliative care), improving access to opioids, and developing regional training capacity in palliative medicine. These developments emphasise the crucial role of public-private partnerships in improving health care for the region and show how fostering strategic collaborations with colleagues and centres in more developed countries, who can contribute specialised expertise and improve regional collaboration, can improve care across the cancer control continuum.

Unexpected findings and misdiagnoses in coroner's autopsies performed for trauma at the University of the West Indies, Kingston, Jamaica.

There has been significant improvement in medical diagnostic technology, but discrepancy rates between clinical and postmortem diagnoses remain relatively high. This study aimed to identify misdiagnoses and missed (unexpected) findings documented during complete coroner's autopsies performed for trauma at the University of the West Indies (UWI) and evaluate their influence on patient outcome. We retrospectively reviewed the reports of all coroner's autopsies performed for trauma, between 2003 and 2012, at the UWI. For each case, we extracted age, gender, trauma type, mechanism and topography, clinical and postmortem diagnoses and hospitalization duration. The data were used to calculate frequencies, proportions and discrepancy rates. 955 coroner's autopsies were performed during the 10-year period; reports were available for 933. 396 of these were performed for trauma; 365 met the inclusion criteria. 260 (71.2%) of the 365 autopsies had at least one discrepancy. There were 746 clinical and 1118 autopsy diagnoses; 382 were discrepant (372 missed [unexpected] diagnoses, 6 mis-diagnoses and 4 over-diagnoses). The discrepancy rate (misdiagnoses and missed diagnoses) was 33.8%, and the majority (55%) occurred in patients hospitalized for <1 day. Cardiopulmonary diseases were the most commonly missed diagnoses. The discrepancy rate was intermediate to those previously reported in the literature. The short hospitalization duration in most patients suggests that limited time for clinical investigation may be a contributor to discrepancy. However, increased awareness among clinicians of the common major missed diagnoses should enhance their early diagnosis, even when clinical signs are subtle, hopefully producing improved patient outcome.

Sinonasal malignancies: incidence and histological distribution in Jamaica, 1973-2007.

PURPOSE: To determine the histological distribution and trends in incidence of sinonasal malignancies in Jamaica. METHODS: Cases of all sinonasal malignancies diagnosed between 1973 and 2007 were extracted from the archives of the Jamaica Cancer Registry. Data recorded for each case included age at diagnosis, sex, year of diagnosis, topography, and histology. Data were used to calculate frequencies, age-specific incidence rates, and age-standardized incidence rates (ASRs). Linear regression analysis was used to determine significance of trends in incidence rates; p values of ≤0.05 were significant. RESULTS: Sinonasal malignancies were commoner in males (male: female ratio, 1.1:1), and the median ages were 62 (males) and 66 years (females). Most were located in either the maxillary sinus (61.3%) or nasal cavity (24.3%). The commonest histological types were squamous cell carcinoma (SCC) (55.9%) and non-Hodgkin's lymphoma (17.1%), which were predominantly of T-cell immunophenotype, in both the nasal cavity and sinuses. There was no documentation in registry data regarding separation into NK/T and peripheral T-subtypes. The ASRs in males and females were consistently less than 1.5 per 100,000 per year. In males, there was a significant decrease in SCC ASR (p = 0.014) over time. CONCLUSIONS: The age, gender, and anatomical and histological distribution patterns of sinonasal malignancies in Jamaica are similar to those reported internationally, and the low ASRs are in keeping with previous global reports. Broader local immunohistochemistry panels are warranted for further delineation of sinonasal T-cell lymphomas. Investigation into factors contributing to the decreasing incidence of sinonasal SCC is also required.

Higher-level phylogeny of the Hymenoptera inferred from mitochondrial genomes.

Higher-level hymenopteran relationships remain unresolved in both morphological and molecular analyses. In this study, we present the most comprehensive analyses of hymenopteran relationships based on 48 mitochondrial (mt) genomes. One complete and two nearly complete mt genomes representing three hymenopteran superfamilies were newly sequenced. We assessed the influence of inclusion/exclusion of 3rd codon positions, alignment approaches, partition schemes and phylogenetic approaches on topology and nodal support within the Hymenoptera. The results showed that the topologies were sensitive to the variation of dataset and analytical approach. However, some robust and highly supported relationships were recovered: the Ichneumonomorpha was monophyletic; the Trigonalyoidea+Megalyroidea and the Diaprioidea+Chalcidoidea were consistently recovered; the Cynipoidea was generally recovered as the sister group to the Diaprioidea+Chalcidoidea. In addition, the monophyletic Aculeata and Proctotrupomorpha were recovered in some analyses. Several gene rearrangements were detected in each of the three newly sequenced mt genomes. Specifically, the Ibalia leucospoides mt genome harbors a large inversion of a gene block from trnE to trnS2. Inverted, duplicated A+T rich regions were detected in the Ibalia leucospoides mt genome, which probably played an important role during the formation of the large gene block inversion via recombination.

Evolutionary dynamics of the mitochondrial genome in the evaniomorpha (hymenoptera)­a group with an intermediate rate of gene rearrangement.

We determined the complete mitochondrial (mt) genomes of three evaniomorph species, Ceraphron sp. (Ceraphronoidea), Gasteruption sp. (Evanioidea), and Orthogonalys pulchella (Trigonalyoidea) as well as the nearly complete mt genome from another evaniomorph species, Megalyra sp. (Megalyroidea). Each of them possesses dramatic gene rearrangements, including protein-coding or rRNA genes. Gene inversions were identified in all of these mt genomes; for example, the two rRNA genes have inverted and moved into the nad2-cox1 junction in the Megalyra sp. mt genome. In addition, we found two copies of a 10-bp complementary repeat at the beginning of rrnS and at the end of trnL(2) in the Gasteruption sp. mt genome, consistent with recombination as the possible mechanism for gene inversion and long-range movement. Although each of the genomes contains a number of repeats of varying size, there was no consistent association of the size or number of repeats with the extent or type of gene rearrangement. The breakpoint distance analysis showed the Evaniomorpha has an intermediate rate of gene rearrangement. Sequence-based phylogenetic analyses of 13 protein-coding and 2 rRNA genes in 22 hymenopteran taxa recovered a paraphyletic Evaniomorpha with the Aculeata nested within it. Within the Evaniomorpha, our analyses confirmed the Trigonalyoidea + Megalyroidea as the sister group to the Aculeata and recovered a novel clade, Ceraphronoidea + Evanioidea. In contrast to previous hymenopteran phylogenetic studies, the internal relationships of the Evaniomorpha were highly supported and robust to the variation of alignment approach and phylogenetic inference approach.

Pathological factors affecting gastric adenocarcinoma survival in a Caribbean population from 2000-2010.

AIM: To investigate pathological factors related to long term patient survival post surgical management of gastric adenocarcinoma in a Caribbean population. METHODS: This is a retrospective, observational study of all patients treated surgically for gastric adenocarcinoma from January 1(st) 2000 to December 31(st) 2010 at The University Hospital of the West Indies, an urban Jamaican hospital. Pathological reports of all gastrectomy specimens post gastric cancer resection during the specified interval were accessed. Patients with a final diagnosis other than adenocarcinoma, as well as patients having undergone surgery at an external institution were excluded. The clinical records of the selected cohort were reviewed. The following variables were analysed; patient gender, patient age, the number of gastrectomies previous performed by the lead surgeon, the gross anatomical location and appearance of the tumour, the histological appearance of the tumour, infiltration of the tumour into stomach wall and surrounding structures, presence of Helicobacter pylori and the presence of gastritis. Patient status as dead vs alive was documented for the end of the interval. The effect of the aforementioned factors on patient survival were analysed using Logrank tests, Cox regression models, Ranksum tests, Kruskal-Wallis tests and Kaplan-Meier curves. RESULTS: A total of 79 patients, 36 males and 43 females, were included. Their median age was 67 years (range 36-86 years). Median survival time from surgery was 70 mo with 40.5% of patients dying before the termination date of the study. Tumours ranged from 0.8 cm in size to encompassing the entire stomach specimen, with a median tumour size of 6 cm. The median number of nodes removed at surgery was 8 with a maximum of 28. The median number of positive lymph nodes found was 2, with a range of 0 to 22. Patients' median survival time was approximately 70 mo, with 40.5% of the patients in this cohort dying before the terminal date. An increase in the incidence of cardiac tumours was noted compared to the previous 10 year interval (7.9% to 9.1%). Patients who had serosal involvement of the tumour did have a significantly shorter survival than those who did not (P = 0.017). A significant increase in the hazard ratio (HR), 2.424, for patients with circumferential tumours was found (P = 0.044). Via Kaplan-Meier estimates, the presence of venous infiltration as well as involvement of the circumferential resection margin were found to be poor prognostic markers, decreasing survival at 50 mo by 46.2% and 36.3% respectively. The increased HR for venous infiltration, 2.424, trended toward significant (P = 0.055) Age, size of tumour, number of positive nodes found and total number of lymph nodes removed were not useful predictors of survival. It is noted that the results were mostly negative, that is many tumour characteristics did not indicate any evidence of affecting patient survival. The current sample, with 30 observed events (deaths), would have about 30% power to detect a HR of 2.5. CONCLUSION: This study mirrors pathological factors used for gastric cancer prognostication in other populations. As evaluation continues, a larger cohort will strengthen the significance of observed trends.

Evidence of animal mtDNA recombination between divergent populations of the potato cyst nematode Globodera pallida.

Recombination is typically assumed to be absent in animal mitochondrial genomes (mtDNA). However, the maternal mode of inheritance means that recombinant products are indistinguishable from their progenitor molecules. The majority of studies of mtDNA recombination assess past recombination events, where patterns of recombination are inferred by comparing the mtDNA of different individuals. Few studies assess contemporary mtDNA recombination, where recombinant molecules are observed as direct mosaics of known progenitor molecules. Here we use the potato cyst nematode, Globodera pallida, to investigate past and contemporary recombination. Past recombination was assessed within and between populations of G. pallida, and contemporary recombination was assessed in the progeny of experimental crosses of these populations. Breeding of genetically divergent organisms may cause paternal mtDNA leakage, resulting in heteroplasmy and facilitating the detection of recombination. To assess contemporary recombination we looked for evidence of recombination between the mtDNA of the parental populations within the mtDNA of progeny. Past recombination was detected between a South American population and several UK populations of G. pallida, as well as between two South American populations. This suggests that these populations may have interbred, paternal mtDNA leakage occurred, and the mtDNA of these populations subsequently recombined. This evidence challenges two dogmas of animal mtDNA evolution; no recombination and maternal inheritance. No contemporary recombination between the parental populations was detected in the progeny of the experimental crosses. This supports current arguments that mtDNA recombination events are rare. More sensitive detection methods may be required to adequately assess contemporary mtDNA recombination in animals.

A Comparison of Three Molecular Markers for the Identification of Populations of Globodera pallida.

Potato cyst nematodes cost the potato industry substantial financial losses annually. Through the use of molecular markers, the distribution and infestation routes of these nematodes can be better elucidated, permitting the development of more effective preventative methods. Here we assess the ability of three molecular markers to resolve multiple representatives of five Globodera pallida populations as monophyletic groups. Molecular markers included a region of the rbp-1 gene (an effector), a non-coding nuclear DNA region (the ITS region), and a novel marker for G. pallida, a ∼3.4 kb non-coding mitochondrial DNA (mtDNA) region. Multiple phylogenetic analysis methods were performed on the three DNA regions separately, and on a data set of these three regions combined. The analyses of the combined data set were similar to that of the sole mtDNA marker; resolving more populations as monophyletic groups, relative to that of the ITS region and rbp-1 gene region. This suggests that individual markers may be inadequate for distinguishing populations of G. pallida. The use of this new non-coding mtDNA marker may provide further insights into the historical distribution of G. pallida, as well as enable the development of more sensitive diagnostic methods.

The mitochondrial genome of the soybean cyst nematode, Heterodera glycines.

We sequenced the entire coding region of the mitochondrial genome of Heterodera glycines. The sequence obtained comprised 14.9 kb, with PCR evidence indicating that the entire genome comprised a single, circular molecule of approximately 21-22 kb. The genome is the most T-rich nematode mitochondrial genome reported to date, with T representing over half of all nucleotides on the coding strand. The genome also contains the highest number of poly(T) tracts so far reported (to our knowledge), with 60 poly(T) tracts ≥ 12 Ts. All genes are transcribed from the same mitochondrial strand. The organization of the mitochondrial genome of H. glycines shows a number of similarities compared with Radopholus similis, but fewer similarities when compared with Meloidogyne javanica. Very few gene boundaries are shared with Globodera pallida or Globodera rostochiensis. Partial mitochondrial genome sequences were also obtained for Heterodera cardiolata (5.3 kb) and Punctodera chalcoensis (6.8 kb), and these had identical organizations compared with H. glycines. We found PCR evidence of a minicircular mitochondrial genome in P. chalcoensis, but at low levels and lacking a noncoding region. Such circularised genome fragments may be present at low levels in a range of nematodes, with multipartite mitochondrial genomes representing a shift to a condition in which these subgenomic circles predominate.

Poly(T) variation in heteroderid nematode mitochondrial genomes is predominantly an artefact of amplification.

We assessed the rate of in vitro polymerase errors at polythymidine [poly(T)] tracts in the mitochondrial DNA (mtDNA) of a heteroderid nematode (Heterodera cajani). The mtDNA of these nematodes contain unusually high numbers of poly(T) tracts, and have previously been suggested to contain biological poly(T) length variation. However, using a cloned molecule, we observed that poly(T) variation was generated in vitro at regions containing more than six consecutive Ts. This artefactual error rate was estimated at 7.3 × 10(-5) indels/poly(T) tract >6 Ts/cycle. This rate was then compared to the rate of poly(T) variation detected after the amplification of a biological sample, in order to estimate the 'biological + artefactual' rate of poly(T) variation. There was no significant difference between the artefactual and the artefactual + biological rates, suggesting that the majority of poly(T) variation in the biological sample was artefactual. We then examined the generation of poly(T) variation in a range of templates with tracts up to 16 Ts long, utilizing a range of Heteroderidae species. We observed that T deletions occurred five times more frequently than insertions, and a trend towards increasing error rates with increasing poly(T) tract length. These findings have significant implications for studies involving genomes with many homopolymer tracts.

Paternal leakage of mitochondrial DNA in experimental crosses of populations of the potato cyst nematode Globodera pallida.

Animal mtDNA is typically assumed to be maternally inherited. Paternal mtDNA has been shown to be excluded from entering the egg or eliminated post-fertilization in several animals. However, in the contact zones of hybridizing species and populations, the reproductive barriers between hybridizing organisms may not be as efficient at preventing paternal mtDNA inheritance, resulting in paternal leakage. We assessed paternal mtDNA leakage in experimental crosses of populations of a cyst-forming nematode, Globodera pallida. A UK population, Lindley, was crossed with two South American populations, P5A and P4A. Hybridization of these populations was supported by evidence of nuclear DNA from both the maternal and paternal populations in the progeny. To assess paternal mtDNA leakage, a ~3.4 kb non-coding mtDNA region was analyzed in the parental populations and in the progeny. Paternal mtDNA was evident in the progeny of both crosses involving populations P5A and P4A. Further, paternal mtDNA replaced the maternal mtDNA in 22 and 40 % of the hybrid cysts from these crosses, respectively. These results indicate that under appropriate conditions, paternal leakage occurs in the mtDNA of parasitic nematodes, and supports the hypothesis that hybrid zones facilitate paternal leakage. Thus, assumptions of strictly maternal mtDNA inheritance may be frequently violated, particularly when divergent populations interbreed.

A practical guide to external direct current cardioversion.

Cardioversion is a procedure used to convert a tachyarrhythmia to normal sinus rhythm by applying a synchronised electric shock. This can be carried out on an elective or urgent basis. The purpose of this article is to provide the reader with a greater understanding of external direct current (DC) cardioversion by exploring some of the theoretical and practical issues associated with the procedure.

A practical guide to external cardiac pacing.

External (transcutaneous) pacing is a temporary means of pacing a patient's heart during an emergency. Pulses of electrical current are delivered through the patient's chest to stimulate the cardiac muscle to contract. It restores electrical stimulation to the myocardium in an emergency setting and its advantage is that it can be initiated quickly by any healthcare professional who has undertaken the necessary training. This article provides the reader with a greater understanding of external pacing by exploring some of the theoretical and practical issues associated with the procedure.

Poly(T) variation within mitochondrial protein-coding genes in Globodera (Nematoda: Heteroderidae).

We sequenced a mitochondrial subgenome from the nematode Globodera rostochiensis, in two overlapping pieces. The subgenome was 9210 bp and contained four protein-coding genes (ND4, COIII, ND3, Cytb) and two tRNA genes (tRNA(Thr), tRNA(Gln)). Genome organization was similar to that of Globodera pallida, which is multipartite. Together with the small number of genes on this subgenome, this suggests that the mitochondrial genome of G. rostochiensis is also multipartite. In the initial clones sequenced, COIII and ND3 were full-length, while ND4 and Cytb were interrupted by premature stop codons and contained point indels that disrupted the reading frame. However, sequencing of multiple clones, from DNA extracted both from multiple individuals and from single cysts, revealed a predominant source of variation-in the length of polythymidine tracts. Comparison of our genomic sequences with ESTs similarly revealed variation in the length of polythymidine tracts. We subsequently sequenced both genomic DNA and mRNA from populations of G. pallida. In each case, variation in the length of polythymidine tracts was observed. The levels of expression of mitochondrial genes in G. pallida were representative of the subgenomes present: little evidence of differential expression was observed. These observations are consistent with the operation of posttranscriptional editing in Globodera mitochondria, although this is difficult to show conclusively in the presence of intraindividual gene sequence variation. Further, alternative explanations cannot be discounted; these include the operation of slippage during translation or that genomic copies of most genes are pseudogenes with a small proportion of full-length sequences able to maintain mitochondrial function.

Sequence and characterization of six mitochondrial subgenomes from Globodera rostochiensis: multipartite structure is conserved among close nematode relatives.

Recently, a multipartite mitochondrial genome was characterized in the potato cyst nematode, Globodera pallida. Six subgenomic circles were detectable by PCR, while full-length genomes were not. We investigate here whether this subgenomic organization occurs in a close relative of G. pallida. We amplified and sequenced one entire mitochondrial subgenome from the cyst-forming nematode, Globodera rostochiensis. Comparison of the noncoding region of this subgenome with those reported previously for G. pallida facilitated the design of amplification primers for a range of subgenomes from G. rostochiensis. We then randomly sequenced five subgenomic fragments, each representative of a unique subgenome. This study indicates that the multipartite structure reported for G. pallida is conserved in G. rostochiensis. A comparison of subgenomic organization between these two Globodera species indicates a considerable degree of overlap between them. Indeed, we identify two subgenomes with an organization identical with that reported for G. pallida. However, other subgenomes are unique to G. rostochiensis, although some of these have blocks of genes comparable to those in G. pallida. Dot-plot comparisons of pairs of subgenomes from G. rostochiensis indicate that the different subgenomes share fragments with high sequence identity. We interpret this as evidence that recombination is operating in the mitochondria of G. rostochiensis.

The mitochondrial subgenomes of the nematode Globodera pallida are mosaics: evidence of recombination in an animal mitochondrial genome.

We sequenced four mitochondrial subgenomes from the potato cyst nematode Globodera pallida, previously characterized as one of the few animals to have a multipartite mitochondrial genome. The sequence data indicate that three of these subgenomic mitochondrial circles are mosaics, comprising long, multigenic fragments derived from fragments of the other circles. This pattern is consistent with the operation of intermitochondrial recombination, a process generally considered absent in animal mitochondria. We also report that many of the duplicated genes contain deleterious mutations, ones likely to render the gene nonfunctional; gene conversion does not appear to be homogenizing the different gene copies. The proposed nonfunctional copies are clustered on particular circles, whereas copies that are likely to code functional gene products are clustered on others.