A New Rodent Model to Assess Blood Stage Immunity to the Plasmodium falciparum Antigen Merozoite Surface Protein 119 Reveals a Protective Role for Invasion Inhibitory Antibodies

Antibodies capable of inhibiting the invasion of Plasmodium merozoites into erythrocytes are present in individuals that are clinically immune to the malaria parasite. Those targeting the 19-kD COOH-terminal domain of the major merozoite surface protein (MSP)-119 are a major component of this inhibitory activity. However, it has been difficult to assess the overall relevance of such antibodies to antiparasite immunity. Here we use an allelic replacement approach to generate a rodent malaria parasite (Plasmodium berghei) that expresses a human malaria (Plasmodium falciparum) form of MSP-119. We show that mice made semi-immune to this parasite line generate high levels of merozoite inhibitory antibodies that are specific for P. falciparum MSP-119. Importantly, protection from homologous blood stage challenge in these mice correlated with levels of P. falciparum MSP-119–specific inhibitory antibodies, but not with titres of total MSP-119–specific immunoglobulins. We conclude that merozoite inhibitory antibodies generated in response to infection can play a significant role in suppressing parasitemia in vivo. This study provides a strong impetus for the development of blood stage vaccines designed to generate invasion inhibitory antibodies and offers a new animal model to trial P. falciparum MSP-119 vaccines

The ENHANCES study--Enhancing Head and Neck Cancer patients' Experiences of Survivorship: study protocol for a randomized controlled trial

Background Few cancers pose greater challenges than head and neck (H&N) cancer. Residual effects following treatment include body image changes, pain, fatigue and difficulties with appetite, swallowing and speech. Depression is a common comorbidity. There is limited evidence about ways to assist patients to achieve optimal adjustment after completion of treatment. In this study, we aim to examine the effectiveness and feasibility of a model of survivorship care to improve the quality of life of patients who have completed treatment for H&N cancer. Methods This is a preliminary study in which 120 patients will be recruited. A prospective randomised controlled trial of the H&N Cancer Survivor Self-management Care Plan (HNCP) involving pre- and post-intervention assessments will be used. Consecutive patients who have completed a defined treatment protocol for H&N cancer will be recruited from two large cancer services and randomly allocated to one of three study arms: (1) usual care, (2) information in the form of a written resource or (3) the HNCP delivered by an oncology nurse who has participated in manual-based training and skill development in patient self-management support. The trained nurses will meet patients in a face-to-face interview lasting up to 60 minutes to develop an individualised HNCP, based on principles of chronic disease self-management. Participants will be assessed at baseline, 3 and 6 months. The primary outcome measure is quality of life. The secondary outcome measures include mood, self-efficacy and health-care utilisation. The feasibility of implementing this intervention in routine clinical care will be assessed through semistructured interviews with participating nurses, managers and administrators. Interviews with patients who received the HNCP will explore their perceptions of the HNCP, including factors that assisted them in achieving behavioural change. Discussion In this study, we aim to improve the quality of life of a patient population with unique needs by means of a tailored self-management care plan developed upon completion of treatment. Delivery of the intervention by trained oncology nurses is likely to be acceptable to patients and, if successful, will be a model of care that can be implemented for diverse patient populations

Phylogeography of the antilopine wallaroo (Macropus antilopinus) across tropical northern Australia

The distribution of antilopine wallaroo, Macropus antilopinus, is marked by a break in the species’ range between Queensland and the Northern Territory, coinciding with the Carpentarian barrier. Previous work on M. antilopinus revealed limited genetic differentiation between the Northern Territory and Queensland M. antilopinus populations across this barrier. The study also identified a number of divergent lineages in the Northern Territory, but was unable to elucidate any geographic structure. Here, we re-examine these results to (1) determine phylogeographic patterns across the range of M. antilopinus and (2) infer the biogeographic barriers associated with these patterns. The tropical savannahs of northern Australia: from the Cape York Peninsula in the east, to the Kimberley in the west. We examined phylogeographic patterns in M. antilopinus using a larger number of samples and three mtDNA genes: NADH dehydrogenase subunit 2, cytochrome b, and the control region. Two datasets were generated and analyzed: (1) a subset of samples with all three mtDNA regions concatenated together and (2) all samples for just control region sequences that included samples from the previous study. Analysis included generating phylogenetic trees based on Bayesian analysis and intraspecific median-joining networks. The contemporary spatial structure of M. antilopinus mtDNA lineages revealed five shallow clades and a sixth, divergent lineage. The genetic differences that we found between Queensland and Northern Territory M. antilopinus samples confirmed the split in the geographic distribution of the species. We also found weak genetic differentiation between Northern Territory samples and those from the Kimberley region of Western Australia, possibly due to the Kimberley Plateau–Arnhem Land barrier. Within the Northern Territory, two clades appear to be parapatric in the west, while another two clades are broadly sympatric across the Northern Territory. MtDNA diversity of M. antilopinus revealed an unexpectedly complex evolutionary history involving multiple sympatric and parapatric mtDNA clades across northern Australia. These phylogeographic patterns highlight the importance of investigating genetic variation across distributions of species and integrating this information into biodiversity conservation

The use of oral fluids to monitor key pathogens in porcine respiratory disease complex.

BACKGROUND: The usefulness of oral fluid (OF) sampling for surveillance of infections in pig populations is already accepted but its value as a tool to support investigations of porcine respiratory disease complex (PRDC) has been less well studied. This study set out to describe detection patterns of porcine reproductive and respiratory syndrome virus (PRRSV), porcine circovirus type 2 (PCV2), swine influenza virus type A (SIV) and Mycoplasma hyopneumoniae (M. hyo) among farms showing differing severity of PRDC. The study included six wean-to-finish pig batches from farms with historical occurrence of respiratory disease. OF samples were collected from six pens every two weeks from the 5th to the 21st week of age and tested by real time PCR for presence of PRRSV, SIV and M. hyo and by quantitative real time PCR for PCV2. Data was evaluated alongside clinical and post-mortem observations, mortality rate, slaughter pathology, histopathology, and immunohistochemistry testing data for PCV2 antigen where available. RESULTS: PRRSV and M. hyo were detectable in OF but with inconsistency between pens at the same sampling time and within pens over sequential sampling times. Detection of SIV in clinical and subclinical cases showed good consistency between pens at the same sampling time point with detection possible for periods of 2-4 weeks. Quantitative testing of OF for PCV2 indicated different patterns and levels of detection between farms unaffected or affected by porcine circovirus diseases (PCVD). There was good correlation of PCR results for multiple samples collected from the same pen but no associations were found between prevalence of positive test results and pen location in the building or sex of pigs. CONCLUSIONS: Detection patterns for PRRSV, SIV and M. hyo supported the effectiveness of OF testing as an additional tool for diagnostic investigation of PRDC but emphasised the importance of sampling from multiple pens and on multiple occasions. Preliminary evidence supported the measurement of PCV2 load in pooled OF as a tool for prediction of clinical or subclinical PCVD at farm level

Smoking in film in New Zealand: measuring risk exposure

BACKGROUND: Smoking in film is a risk factor for smoking uptake in adolescence. This study aimed to quantify exposure to smoking in film received by New Zealand audiences, and evaluate potential interventions to reduce the quantity and impact of this exposure. METHODS: The ten highest-grossing films in New Zealand for 2003 were each analysed independently by two viewers for smoking, smoking references and related imagery. Potential interventions were explored by reviewing relevant New Zealand legislation, and scientific literature. RESULTS: Seven of the ten films contained at least one tobacco reference, similar to larger film samples. The majority of the 38 tobacco references involved characters smoking, most of whom were male. Smoking was associated with positive character traits, notably rebellion (which may appeal to adolescents). There appeared to be a low threshold for including smoking in film. Legislative or censorship approaches to smoking in film are currently unlikely to succeed. Anti-smoking advertising before films has promise, but experimental research is required to demonstrate cost effectiveness. CONCLUSION: Smoking in film warrants concern from public health advocates. In New Zealand, pre-film anti-smoking advertising appears to be the most promising immediate policy response

Hybrid III-V on silicon lasers for photonic integrated circuits on silicon

This paper summarizes recent advances of integrated hybrid InP/SOI lasers and transmitters based on wafer bonding. At first the integration process of III-V materials on silicon is described. Then the paper reports on the results of single wavelength distributed Bragg reflector lasers with Bragg gratings etched on silicon waveguides. We then demonstrate that, thanks to the high-quality silicon bend waveguides, hybrid III-V/Si lasers with two integrated intra-cavity ring resonators can achieve a wide thermal tuning range, exceeding the C band, with a side mode suppression ratio higher than 40 dB. Moreover, a compact array waveguide grating on silicon is integrated with a hybrid III-V/Si gain section, creating a wavelength-selectable laser source with 5 wavelength channels spaced by 400 GHz. We further demonstrate an integrated transmitter with combined silicon modulators and tunable hybrid III-V/Si lasers. The integrated transmitter exhibits 9 nm wavelength tunability by heating an intra-cavity ring resonator, high extinction ratio from 6 to 10 dB, and excellent bit-error-rate performance at 10 Gb/s

Tissue engineering: state of the art in oral rehabilitation

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/74998/1/j.1365-2842.2009.01939.x.pd

Use of chemotherapy in patients with oesophageal, stomach, colon, rectal, liver, pancreatic, lung, and ovarian cancer: an International Cancer Benchmarking Partnership (ICBP) population-based study

BACKGROUND: There are few data on international variation in chemotherapy use, despite it being a key treatment type for some patients with cancer. Here, we aimed to examine the presence and size of such variation. METHODS: This population-based study used data from Norway, the four UK nations (England, Northern Ireland, Scotland, and Wales), eight Canadian provinces (Alberta, British Columbia, Manitoba, Newfoundland and Labrador, Nova Scotia, Ontario, Prince Edward Island, and Saskatchewan), and two Australian states (New South Wales and Victoria). Patients aged 15-99 years diagnosed with cancer in eight different sites (oesophageal, stomach, colon, rectal, liver, pancreatic, lung, or ovarian cancer), with no other primary cancer diagnosis occurring from within the 5 years before to 1 year after the index cancer diagnosis or during the study period were included in the study. We examined variation in chemotherapy use from 31 days before to 365 days after diagnosis and time to its initiation, alongside related variation in patient group differences. Information was obtained from cancer registry records linked to clinical or patient management system data or hospital administration data. Random-effects meta-analyses quantified interjurisdictional variation using 95% prediction intervals (95% PIs). FINDINGS: Between Jan 1, 2012, and Dec 31, 2017, of 893 461 patients with a new diagnosis of one of the studied cancers, 111 569 (12·5%) did not meet the inclusion criteria, and 781 892 were included in the analysis. There was large interjurisdictional variation in chemotherapy use for all studied cancers, with wide 95% PIs: 47·5 to 81·2 (pooled estimate 66·4%) for ovarian cancer, 34·9 to 59·8 (47·2%) for oesophageal cancer, 22·3 to 62·3 (40·8%) for rectal cancer, 25·7 to 55·5 (39·6%) for stomach cancer, 17·2 to 56·3 (34·1%) for pancreatic cancer, 17·9 to 49·0 (31·4%) for lung cancer, 18·6 to 43·8 (29·7%) for colon cancer, and 3·5 to 50·7 (16·1%) for liver cancer. For patients with stage 3 colon cancer, the interjurisdictional variation was greater than that for all patients with colon cancer (95% PI 38·5 to 78·4; 60·1%). Patients aged 85-99 years had 20-times lower odds of chemotherapy use than those aged 65-74 years, with very large interjurisdictional variation in this age difference (odds ratio 0·05; 95% PI 0·01 to 0·19). There was large variation in median time to first chemotherapy (from diagnosis date) by cancer site, with substantial interjurisdictional variation, particularly for rectal cancer (95% PI -15·5 to 193·9 days; pooled estimate 89·2 days). Patients aged 85-99 years had slightly shorter median time to first chemotherapy compared with those aged 65-74 years, consistently between jurisdictions (-3·7 days, 95% PI -7·6 to 0·1). INTERPRETATION: Large variation in use and time to chemotherapy initiation were observed between the participating jurisdictions, alongside large and variable age group differences in chemotherapy use. To guide efforts to improve patient outcomes, the underlying reasons for these patterns need to be established. FUNDING: International Cancer Benchmarking Partnership (funded by the Canadian Partnership Against Cancer, Cancer Council Victoria, Cancer Institute New South Wales, Cancer Research UK, Danish Cancer Society, National Cancer Registry Ireland, The Cancer Society of New Zealand, National Health Service England, Norwegian Cancer Society, Public Health Agency Northern Ireland on behalf of the Northern Ireland Cancer Registry, DG Health and Social Care Scottish Government, Western Australia Department of Health, and Public Health Wales NHS Trust)