Completeness of case ascertainment and survival time error in English cancer registries: impact on 1-year survival estimates.

BACKGROUND: It has been suggested that cancer registries in England are too dependent on processing of information from death certificates, and consequently that cancer survival statistics reported for England are systematically biased and too low. METHODS: We have linked routine cancer registration records for colorectal, lung, and breast cancer patients with information from the Hospital Episode Statistics (HES) database for the period 2001-2007. Based on record linkage with the HES database, records missing in the cancer register were identified, and dates of diagnosis were revised. The effects of those revisions on the estimated survival time and proportion of patients surviving for 1 year or more were studied. Cases that were absent in the cancer register and present in the HES data with a relevant diagnosis code and a relevant surgery code were used to estimate (a) the completeness of the cancer register. Differences in survival times calculated from the two data sources were used to estimate (b) the possible extent of error in the recorded survival time in the cancer register. Finally, we combined (a) and (b) to estimate (c) the resulting differences in 1-year cumulative survival estimates. RESULTS: Completeness of case ascertainment in English cancer registries is high, around 98-99%. Using HES data added 1.9%, 0.4% and 2.0% to the number of colorectal, lung, and breast cancer registrations, respectively. Around 5-6% of rapidly fatal cancer registrations had survival time extended by more than a month, and almost 3% of rapidly fatal breast cancer records were extended by more than a year. The resulting impact on estimates of 1-year survival was small, amounting to 1.0, 0.8, and 0.4 percentage points for colorectal, lung, and breast cancer, respectively. INTERPRETATION: English cancer registration data cannot be dismissed as unfit for the purpose of cancer survival analysis. However, investigators should retain a critical attitude to data quality and sources of error in international cancer survival studies

A Multi-Parametric Imaging Investigation of the Response of C6 Glioma Xenografts to MLN0518 (Tandutinib) Treatment.

Angiogenesis, the development of new blood vessels, is essential for tumour growth; this process is stimulated by the secretion of numerous growth factors including platelet derived growth factor (PDGF). PDGF signalling, through its receptor platelet derived growth factor receptor (PDGFR), is involved in vessel maturation, stimulation of angiogenesis and upregulation of other angiogenic factors, including vascular endothelial growth factor (VEGF). PDGFR is a promising target for anti-cancer therapy because it is expressed on both tumour cells and stromal cells associated with the vasculature. MLN0518 (tandutinib) is a potent inhibitor of type III receptor tyrosine kinases that demonstrates activity against PDGFRα/β, FLT3 and c-KIT. In this study a multi-parametric MRI and histopathological approach was used to interrogate changes in vascular haemodynamics, structural response and hypoxia in C6 glioma xenografts in response to treatment with MLN0518. The doubling time of tumours in mice treated with MLN0518 was significantly longer than tumours in vehicle treated mice. The perfused vessel area, number of alpha smooth muscle actin positive vessels and hypoxic area in MLN0518 treated tumours were also significantly lower after 10 days treatment. These changes were not accompanied by alterations in vessel calibre or fractional blood volume as assessed using susceptibility contrast MRI. Histological assessment of vessel size and total perfused area did not demonstrate any change with treatment. Intrinsic susceptibility MRI did not reveal any difference in baseline R2* or carbogen-induced change in R2*. Dynamic contrast-enhanced MRI revealed anti-vascular effects of MLN0518 following 3 days treatment. Hypoxia confers chemo- and radio-resistance, and alongside PDGF, is implicated in evasive resistance to agents targeted against VEGF signalling. PDGFR antagonists may improve potency and efficacy of other therapeutics in combination. This study highlights the challenges of identifying appropriate quantitative imaging response biomarkers in heterogeneous models, particularly considering the multifaceted roles of angiogenic growth factors

Resolution of Thylakoid Polyphenol Oxidase and a Protein Kinase

The predominant protein kinase activity in octylglucoside (OG) extracts of spinach thylakoids has been attributed to a 64-kDa protein, tp64. Recent work calls into question the relation between tp64 and protein kinase activity, which were fractionated apart using fluid phase IEF and hydroxylapatite chromatography. Hind et al. sequenced tp64 from the cDNA and showed it to be a polyphenol oxidase (PPO) homolog. Its transit peptide indicates a location for the mature protein within the thylakoid lumen, where there is presumably no ATP and where it is remote from the presumed kinase substrates: the stromally exposed regions of integral PS-II membrane proteins. Here the authors suggest that the kinase is a 64-kDa protein distinct from tp64

Montreal Cognitive Assessment (MoCA): Normative Data for the State of Kerala, South India

\ua9 2024 Wolters Kluwer Medknow Publications. All rights reserved.Background: Montreal cognitive assessment (MoCA) is a tool that is widely accepted across the world to measure mild cognitive impairment (MCI). The original cut-off score of MoCA falsely screens a large population of Indians as having MCI. Objective: The aim of this study was to develop the normative data for MoCA for the older population of Kerala, South India. Material and Methods: We conducted the study among 959 cognitively normal older individuals of Kalliyoor village of Thiruvananthapuram district, Kerala. The validated Malayalam version of MoCA [MoCA-M] was administered by trained volunteers. The mean, median, and 10 th percentile of the scores [domain-specific and total] were calculated in various age and educational groups. Results: The mean (SD) MoCA score was 19.4 (7.3). The 10 th percentile for the total MoCA score was 9. The 10 th percentile for all domains was zero, except for orientation. As age advanced, MoCA scores significantly reduced. The mean total MoCA scores dropped from 20.1 (7) [for ages between 65 and 75 years] to 7.4 (1.6) [for ages above 85 years]. We also obtained a significant improvement in scores among subjects with higher educational standards. Conclusion: The study throws light into the performance of MoCA among the Indian population. This study defines the norms for the Indian population and suggests redefining the threshold for positively screening for MCI using MoCA-M

Whole-body dynamic stability in side cutting: implications for markers of lower limb injury risk and change of direction performance

Control of the centre of mass (CoM) whilst minimising the use of unnecessary movements is imperative for successful performance of dynamic sports tasks, and may indicate the condition of whole-body dynamic stability. The aims of this study were to express movement strategies that represent whole-body dynamic stability, and to explore their association with potentially injurious joint mechanics and side cutting performance. Twenty recreational soccer players completed 45° unanticipated side cutting. Five distinct whole-body dynamic stability movement strategies were identified, based on factors that influence the medial ground reaction force (GRF) vector during ground contact in the side cutting manoeuvre. Using Statistical Parametric Mapping, the movement strategies were linearly regressed against selected performance outcomes and peak knee abduction moment (peak KAM). Significant relationships were found between each movement strategy and at least one selected performance outcome or peak KAM. Our results suggest excessive medial GRFs were generated through sagittal plane movement strategies, and despite being beneficial for performance aspects, poor sagittal plane efficiency may destabilise control of the CoM. Frontal plane hip acceleration is the key non-sagittal plane movement strategy used in a corrective capacity to moderate excessive medial forces. However, whilst this movement strategy offered a way to retrieve control of the CoM, mitigating reduced whole-body dynamic stability, it also coincided with increased peak KAM. Overall, whole-body dynamic stability movement strategies helped explain the delicate interplay between the mechanics of changing direction and undesirable joint moments, providing insights that might support development of future intervention strategies

The HIF-pathway inhibitor NSC-134754 induces metabolic changes and anti-tumour activity while maintaining vascular function.

BACKGROUND: Hypoxia-inducible factor-1 (HIF-1) mediates the transcriptional response to hypoxic stress, promoting tumour progression and survival. This study investigated the acute effects of the small-molecule HIF-pathway inhibitor NSC-134754. METHODS: Human PC-3LN5 prostate cancer cells were treated with NSC-134754 for 24 h in hypoxia. Orthotopic prostate tumour-bearing mice were treated with a single dose of NSC-134754 for 6, 24 or 48 h. Treatment response was measured using magnetic resonance spectroscopy and imaging. Ex-vivo histological validation of imaging findings was also sought. RESULTS: In vitro, NSC-134754 significantly reduced lactate production and glucose uptake (P<0.05), while significantly increasing intracellular glucose (P<0.01) and glutamine uptake/metabolism (P<0.05). Increased glutamine metabolism was independent of c-Myc, a factor also downregulated by NSC-134754. In vivo, a significantly higher tumour apparent diffusion coefficient was determined 24 h post-treatment (P<0.05), with significantly higher tumour necrosis after 48 h (P<0.05). NSC-134754-treated tumours revealed lower expression of HIF-1α and glucose transporter-1, at 6 and 24 h respectively, while a transient increase in tumour hypoxia was observed after 24 h. Vessel perfusion/flow and vascular endothelial growth factor levels were unchanged with treatment. CONCLUSION: NSC-134754 induces metabolic alterations in vitro and early anti-tumour activity in vivo, independent of changes in vascular function. Our data support the further evaluation of NSC-134754 as an anti-cancer agent

Monitoring the vascular response and resistance to sunitinib in renal cell carcinoma in vivo with susceptibility contrast MRI

Antiangiogenic therapy is efficacious in metastatic renal cell carcinoma (mRCC). However, the ability of antiangiogenic drugs to delay tumor progression and extend survival is limited, due to either innate or acquired drug resistance. Furthermore, there are currently no validated biomarkers that predict which mRCC patients will benefit from antiangiogenic therapy. Here, we exploit susceptibility contrast MRI (SC-MRI) using intravascular ultrasmall superparamagnetic iron oxide particles to quantify and evaluate tumor fractional blood volume (fBV) as a noninvasive imaging biomarker of response to the antiangiogenic drug sunitinib. We also interrogate the vascular phenotype of RCC xenografts exhibiting acquired resistance to sunitinib. SC-MRI of 786-0 xenografts prior to and 2 weeks after daily treatment with 40 mg/kg sunitinib revealed a 71% (P < 0.01) reduction in fBV in the absence of any change in tumor volume. This response was associated with significantly lower microvessel density (P < 0.01) and lower uptake of the perfusion marker Hoechst 33342 (P < 0.05). The average pretreatment tumor fBV was negatively correlated (R2 = 0.92, P < 0.0001) with sunitinib-induced changes in tumor fBV across the cohort. SC-MRI also revealed suppressed fBV in tumors that acquired resistance to sunitinib. In conclusion, SC-MRI enabled monitoring of the antiangiogenic response of 786-0 RCC xenografts to sunitinib, which revealed that pretreatment tumor fBV was found to be a predictive biomarker of subsequent reduction in tumor blood volume in response to sunitinib, and acquired resistance to sunitinib was not associated with a parallel increase in tumor blood volume

Behavioural responses in a congested sea: an observational study on a coastal nest-guarding fish

The deleterious effects of anthropogenic noise on animal communication are nowadays recognised, not only in urban environments but also in terrestrial habitats and along coasts and in open waters. Yet, the assessment of short- and long-term exposure consequences of anthropogenic noise in marine organisms remains challenging, especially in fish and invertebrates. Males of the Mediterranean damselfish Chromis chromis vocalise and perform visual displays (multimodal communication) to attract mates. The frequency-range of courtship vocalisations overlaps with low-frequency noise generated by maritime activities, resulting in a reduced detection distance among conspecifics. We quantified the number of courtship-related visual displays performed by males living in areas with different levels of maritime traffic. We also tried to manipulate ambient noise in the field to test male short-term response to increased noise levels. Males living in busier areas (near to a harbour) performed significantly more visual displays than those living in less congested areas. When exposed to artificially-increased ambient noise level (playback of boat noise), males did not adjust the number of visual displays accordingly. Yet, we note how assessing the actual effect of maritime traffic in marine populations in their natural environments is particularly difficult, as the effects of boat noise cannot be easily disentangled from a variety of other intrinsic or environmental factors, discussed in the paper. We thus present suggestions to obtain more robust analyses of variations of courtship behaviours in territorial fishes. We hope this will facilitate a further understanding of the potential long-term effects of anthropogenic noise, whose analyses should be prioritised in the context of environmental impact assessment, resource management and biodiversity conservation

Experiences of recently HIV-diagnosed gay and bisexual migrants in Australia: Implications for sexual health programmes and health promotion

Gay and bisexual migrants from low- and middle-income countries living in high-income countries are disproportionately diagnosed with HIV. Most research focuses on preventing HIV acquisition among HIV-negative migrant gay and bisexual men (GBM). This study is uniquely positioned to report on migrant GBM's experiences and needs at and after an HIV diagnosis. Semi-structured interviews were conducted with 24 migrant GBM diagnosed at sexual health clinics in Australia from 2017 onwards. Interviews were analysed using a codebook thematic analysis. Due to the stigma of HIV and homosexuality in their countries of origin, about half of participants had poor HIV knowledge prior to diagnosis. Absorbing diagnosis information was consequently difficult, and feelings of shame, hopelessness, lost sexual opportunities and infectiousness were common. However, many were thankful for the comprehensive clinical support they received and believed that over time life would ‘normalise’ with sustained undetectable viral load. None reported that their clinician stigmatised them, but the anticipation of stigma nonetheless infused their experiences after diagnosis. Many were selective about HIV disclosure, and some mentioned that clinic systems posed a risk to confidentiality. Non-permanent residents were concerned about the impacts of HIV status on future visa applications. We recommend that newly HIV-diagnosed migrant GBM receive referral to legal and culturally appropriate migration services to help absorb what a diagnosis might mean for their health and visa status. We also recommend sexual health clinics continue to assess confidentiality in their systems. Health promotion initiatives should highlight to migrant GBM that high-HIV caseload sexual health clinicians provide confidential and comprehensive care