Background: Data on the relationship between plasma levels of cholesterol and triglycerides and social class have been inconsistent. Most previous studies have used one classification of social class. Methods: This was a cross-sectional population based study with data on occupational social class, educational level obtained using a detailed health and lifestyle questionnaire. A total of 10,147 men and 12,304 women aged 45–80 years living in Norfolk, United Kingdom, were recruited using general practice age-sex registers as part of the European Prospective Investigation into Cancer (EPIC-Norfolk). Plasma levels of cholesterol and triglycerides were measured in baseline samples. Social class was classified according to three classifications: occupation, educational level, and area deprivation score according to Townsend deprivation index. Differences in lipid levels by socio-economic status indices were quantified by analysis of variance (ANOVA) and multiple linear regression after adjusting for body mass index and alcohol consumption. Results: Total cholesterol levels were associated with occupational level among men, and with educational level among women. Triglyceride levels were associated with educational level and occupational level among women, but the latter association was lost after adjustment for age and body mass index. HDL-cholesterol levels were associated with both educational level and educational level among men and women. The relationships with educational level were substantially attenuated by adjustment for age, body mass index and alcohol use, whereas the association with educational class was retained upon adjustment. LDL-cholesterol levels were not associated with social class indices among men, but a positive association was observed with educational class among women. This association was not affected by adjustment for age, body mass index and alcohol use. Conclusions: The findings of this study suggest that there are sex differences in the association between socio-economic status and serum lipid levels. The variations in lipid profile with socio-economic status may be largely attributed to potentially modifiable factors such as obesity, physical activity and dietary intake.
Assessment of the quality of studies is a critical component of evidence syntheses such as systematic reviews (SRs) that are used to inform policy decisions. To reduce the potential for reviewer bias, and to ensure that the findings of SRs are transparent and reproducible, organisations such as the Cochrane Collaboration, the Campbell Collaboration, and the Collaboration for Environmental Evidence, recommend the use of formal quality assessment tools as opposed to informal expert judgment. However, there is a bewildering array of around 300 formal quality assessment tools that have been identified in the literature, and it has been demonstrated that the use of different tools for the assessment of the same studies can result in different estimates of quality, which can potentially reverse the conclusions of a SR. It is therefore important to consider carefully, the choice of quality assessment tool. We argue that quality assessment tools should: (1) have proven construct validity (i.e. the assessment criteria have demonstrable link with what they purport to measure), (2) facilitate inter-reviewer agreement, (3) be applicable across study designs, and (4) be quick and easy to use. Our aim was to examine current best practice for quality assessment in healthcare and investigate the extent to which these best practices could be useful for assessing the quality of environmental science studies. The feasibility of this transfer is demonstrated in a number of existing SRs on environmental topics. We propose that environmental practitioners should revise, test and adopt the best practice quality assessment tools used in healthcare as a recommended approach for application to environmental science. We provide pilot versions of quality assessment tools, modified from the best practice tools used in healthcare, for application on studies from environmental science.
There are upcoming non-volatile (NV) memory technologies that provide byte addressability and high performance. PCM, MRAM, and STT-RAM are such examples. Such NV memory can be used as storage because of its data persistency without power supply while it can be used as main memory because of its high performance that matches up with DRAM. There are a number of researches that investigated its uses for main memory and storage. They were, however, conducted independently. This paper presents the methods that enables the integration of the main memory and file system management for NV memory. Such integration makes NV memory simultaneously utilized as both main memory and storage. The presented methods use a file system as their basis for the NV memory management. We implemented the proposed methods in the Linux kernel, and performed the evaluation on the QEMU system emulator. The evaluation results show that 1) the proposed methods can perform comparably to the existing DRAM memory allocator and significantly better than the page swapping, 2) their performance is affected by the internal data structures of a file system, and 3) the data structures appropriate for traditional hard disk drives do not always work effectively for byte addressable NV memory. We also performed the evaluation of the effects caused by the longer access latency of NV memory by cycle-accurate full-system simulation. The results show that the effect on page allocation cost is limited if the increase of latency is moderate.
Background: Acute exacerbation of idiopathic pulmonary fibrosis (AE-IPF) is associated with high mortality. However, few studies have so far reviewed analyses of autopsy findings in patients with AE-IPF. Methods: We retrospectively reviewed 52 consecutive patients with AE-IPF who underwent autopsies at five university hospitals and one municipal hospital between 1999 and 2013. The following variables were abstracted from the medical records: demographic and clinical data, autopsy findings and complications during the clinical course until death. Results: The median age at autopsy was 71?years (range 47?86 years), and the subjects included 38 (73.1%) males. High-dose corticosteroid therapy was initiated in 45 (86.5%) patients after AE-IPF. The underling fibrotic lesion was classified as having the usual interstitial pneumonia (UIP) pattern in all cases. Furthermore, 41 (78.8%) patients had diffuse alveolar damage (DAD), 15 (28.8%) exhibited pulmonary hemorrhage, nine (17.3%) developed pulmonary thromboembolism and six (11.5%) were diagnosed with lung carcinoma. In addition, six (11.5%) patients developed pneumothorax prior to death and 26 (53.1%) developed diabetes that required insulin treatment after the administration of high-dose corticosteroid therapy. In addition, 15 (28.8%) patients presented with bronchopneumonia during their clinical course and/or until death, including fungal (seven, 13.5%), cytomegalovirus (six, 11.5%) and bacterial (five, 9.6%) infections. Conclusions: The pathological findings in patients with AE-IPF represent not only DAD, but also a variety of pathological conditions. Therefore, making a diagnosis of AE-IPF is often difficult, and the use of cautious diagnostic approaches is required for appropriate treatment.
Background: Afghanistan is the 15th least developed country in the world, with poor sanitation and high rates of infectious diseases and malnutrition. However, little is known about the health of young Afghan refugees resettling in Western countries. Methods: We used a cross-sectional study design to examine the health profile of newly arrived Afghan refugees presenting to a General Practice between 20th April 2010 and 22nd March 2013 in rural Australia. Data collected included information on nutritional status and prevalence of infectious diseases. Challenges associated with health screening in a General Practice setting in this population were also documented. Results: Data were available on 92 patients. Mean age of presentation was 22.6 years [SD 11.9], and the majority of patients were male (88%). Mean total cholesterol, LDL cholesterol, HDL cholesterol and triglyceride concentrations were 4.4 mmol/L (95% CI, 2.9-7.3), 2.6 mmol/L (95% CI, 1.3-4.4), 1.24 mmol/L (95% CI, 0.7-2.0) and 1.19 mmol/L (95% CI, 0.4-4.7) respectively, and dyslipidaemia (defined as elevated total or low-density lipoprotein (LDL) cholesterol levels, or low levels of high-density lipoprotein (HDL) cholesterol) was seen in 27.5% of patients. There was also a high prevalence of vitamin D and B12 deficiency (50% and 18%, respectively) in this cohort. Issues that impacted on provision and access to health care for refugees included cost, language barriers, patient mobility and mental health issues. Conclusions: Dyslipidaemia and micronutrient deficiencies are significant health issues in young recently settled Afghan refugees, and routine screening should be considered for this population.
Background: Acupuncture has been shown to reduce pain, and acupuncture-induced sensation may be important for this analgesia. In addition, cognitive coping strategies can influence sensory perception. However, the role of coping strategy on acupuncture modulation of pain and sensory thresholds, and the association between acupuncture sensation and these modulatory effects, is currently unknown. Methods: Electroacupuncture (EA) was applied at acupoints ST36 and GB39 of 61 healthy adults. Different coping conditions were experimentally designed to form an active coping strategy group (AC group), who thought they could control EA stimulation intensity, and a passive coping strategy group (PC group), who did not think they had such control. Importantly, neither group was actually able to control EA stimulus intensity. Quantitative sensory testing was performed before and after EA, and consisted of vibration (VDT), mechanical (MDT), warm (WDT), and cold (CDT) detection thresholds, and pressure (PPT), mechanical (MPT), heat (HPT) and cold (CPT) pain thresholds. Autonomic measures (e.g. skin conductance response, SCR) were also acquired to quantify physiological response to EA under different coping conditions. Subjects also reported the intensity of any acupuncture-induced sensations. Results: Coping strategy was induced with successful blinding in 58% of AC subjects. Compared to PC, AC showed greater SCR to EA. Under AC, EA reduced PPT and CPT. In the AC group, improved pain and sensory thresholds were correlated with acupuncture sensation (VDTchange vs. MI: r=0.58, CDTchange vs. tingling: r=0.53, CPTchange vs. tingling; r=0.55, CPTchange vs. dull; r=0.55). However, in the PC group, improved sensory thresholds were negatively correlated with acupuncture sensation (CDTchange vs. intensity sensitization: r=-0.52, WDTchange vs. fullness: r=-0.57). Conclusions: Our novel approach was able to successfully induce AC and PC strategies to EA stimulation. The interaction between psychological coping strategy and acupuncture sensation intensity can differentially modulate pain and sensory detection threshold response to EA. In a clinical context, our findings suggest that instructions given to the patient can significantly affect therapeutic outcomes and the relationship between acupuncture intensity and clinical response. Specifically, acupuncture analgesia can be enhanced by matching physical stimulation intensity with psychological coping strategy to acupuncture contexts.Trial registration: KCT0000905
Background: Neoadjuvant treatment plays a crucial role in the therapy of advanced esophageal cancer. However, response to radiochemotherapy varies widely. Proton pump inhibitors (PPIs) have been demonstrated to impact on chemotherapy in a variety of other cancers. We analyzed the impact of PPI treatment on esophageal cancer cell lines, and investigated mechanisms that mediate the effect of PPI treatment in this tumour. Methods: We investigated the effect of esomeprazole treatment on cancer cell survival, adhesion, migration and chemotherapy in human adeno-(OE19) and squamous-cell-carcinoma (KYSE410) cell lines. Furthermore, we investigated the effect of PPI treatment on intra-/extracellular pH and on expression of resistance-relevant miRNAs. Results: Esomeprazole significantly inhibited tumour cell survival (in a dose-dependent manner), adhesion and migration in both tumour subtypes. Furthermore, esomeprazole augmented the cytotoxic effect of cisplatin and 5-FU in both tumour subtypes. Surprisingly, PPI treatment led to a significant increase of intracellular pH and a decrease of the extracellular pH. Finally, we found esomeprazole affected expression of resistance-relevant miRNAs. Specifically, miR-141 and miR-200b were upregulated, whereas miR-376a was downregulated after PPI treatment in both tumour types. Conclusion: Our study demonstrates for the first time that PPIs impact on tumour cell survival, metastatic potential and sensitivity towards chemotherapy in esophageal cancer cell lines. Furthermore, we observed that in this tumour entity, PPIs do not lead to intracellular acidification, but affect the expression of resistance-relevant miRNAs.
Background: Biotinidase deficiency (BD) is an inborn error of metabolism in which some genetic variants correlate with the level of enzyme activity. Biotinidase activity, however, may be artifactually low due to enzyme lability, premature birth, and jaundice; this hinders both phenotypic classification and the decision to implement therapy. This study sought to characterize the clinical and genetic profile of a sample of Brazilian patients exhibiting reduced biotinidase activity. Methods: This observational, multicenter study used a convenience sampling strategy, with sequencing of exons 2, 3, and 4 of the BTD gene. Results: The sample comprised 38 individuals with biochemical phenotypes defined a priori on the basis of biotinidase activity in serum/plasma (2 with profound deficiency, 9 with partial deficiency, 15 heterozygous, 1 borderline between partial deficiency and heterozygosity, 2 borderline between heterozygous and normal) or dried blood spot sample (n?=?9, all with unspecified deficiency). Most patients were from Southern Brazil (n?=?29/38) and were identified by neonatal screening (n?=?33/38). Parental consanguinity was reported in two cases. The most commonly found genetic variants were c.1330G?>?C (p.D444H), c.755A?>?G (p.D252G), and c.[511G?>?A;1330G?>?C] (p.[A171T;D444H]), with allele frequencies of 50%, 9.4%, and 5.4% respectively. Three novel pathogenic variants were identified (c.119?T?>?C or p.L40P, c.479G?>?A or p.C160Y, and c.664G?>?A or p.D222N). Twenty-nine patients had two pathogenic variants detected (with cis/trans status ascertained in 26/29), six had only one variant, and three had no pathogenic variants detected. Genotyping confirmed the original phenotypic classification based on enzyme activity in 16/26 cases. Three polymorphic variants were identified in control individuals, of which two were nonpathogenic (c.1171C?>?T or p.P391S and c.1413?T?>?C or p.C471C, with a frequency of 1.5% and 5.5% respectively) and one pathogenic (c.1330G?>?C, frequency 4%). Conclusions: Our findings suggest that partial BD is the most common form of BD in Brazil, and expand current knowledge on the allelic heterogeneity of this condition.
Background: In resource limited settings access to laboratory monitoring of HIV treatment is limited and therapeutic drug monitoring is generally unavailable. This study aimed to evaluate nevirapine concentrations in saliva using low-cost thin-layer chromatography (TLC) and nevirapine concentrations in plasma and saliva using high performance liquid chromatography (HPLC) methods; and to correlate nevirapine plasma concentrations to HIV treatment outcomes in Ugandan patients. Methods: Paired plasma and stimulated saliva samples were obtained from Ugandan, HIV-infected adults on nevirapine-based ART. Nevirapine concentrations were measured using a validated HPLC method and a novel TLC method. Plasma nevirapine concentrations 400 copies/mL. Patients with nevirapine concentrations in plasma 400 copies/mL). Conclusions: The low-cost TLC technique for monitoring nevirapine in saliva was unsuccessful but monitoring nevirapine saliva and plasma concentrations using HPLC was shown to be feasible in the research/specialist context in Uganda. Further optimization and validation is required for the low-cost TLC technique.
Background: Large genomic rearrangements (LGRs) in the BRCA1/2 genes are frequently observed in breast cancer patients who are negative for BRCA1/2 small mutations. Here, we examined 221 familial breast cancer patients from 37 hospitals to estimate the contribution of LGRs, in a nationwide context, to the development of breast cancer. Methods: Direct sequencing or mutation scanning followed by direct sequencing was performed to screen small mutations. BRCA1/2 small mutation-negative patients were screened for the presence of LGRs using a multiple ligation-dependent probe amplification (MLPA) assay. Results: Using a combined strategy to detect the presence of small mutations and LGRs, we identified BRCA1/2 small mutations in 78 (35.3%) out of 221 familial breast cancer patients and BRCA1 LGRs in 3 (2.1%) out of 143 BRCA1/2 small mutation-negative patients: the deletion of exons 11-13, the deletion of exons 13-15, and whole gene deletion of exons 1-24. The novel deletion of exons 11-13 is thought to result from a non-homologous recombination event mediated by a microhomology sequence comprised of 3 or 4 base pairs: c.3416_4357 + 1863delins187 (NG_005905.2: g.33369_44944delins187). Conclusions: In this study, we showed that LGRs were found in 3.7% (3/81) of the patients who had mutations in BRCA1 or BRCA2, and 7.5% (3/40) of patients with mutations in BRCA1. This suggests that the contribution of LGRs to familial breast cancer in this population might be comparable to that in other ethnic populations. Given these findings, an MLPA to screen for mutations in the BRCA1 gene is recommended as an initial screening test in highly selective settings.