National malaria prevalence in Cambodia: microscopy versus polymerase chain reaction estimates

Accurate information regarding malaria prevalence at national level is required to design and assess malaria control/elimination efforts. Although many comparisons of microscopy and polymerase chain reaction (PCR)-based methods have been conducted, there is little published literature covering such comparisons in southeast Asia especially at the national level. Both microscopic examination and PCR detection were performed on blood films and dried blood spots samples collected from 8,067 individuals enrolled in a nationwide, stratified, multistage, cluster sampling malaria prevalence survey conducted in Cambodia in 2007. The overall malaria prevalence and prevalence rates of Plasmodium falciparum, Plasmodium vivax, and Plasmodium malariae infections estimated by microscopy (N = 8,067) were 2.74% (95% confidence interval [CI]: 2.39-3.12%), 1.81% (95% CI: 1.53-2.13%), 1.14% (95% CI: 0.92-1.40%), and 0.01% (95% CI: 0.003-0.07%), respectively. The overall malaria prevalence based on PCR detection (N = 7,718) was almost 2.5-fold higher (6.31%, 95% CI: 5.76-6.89%, P < 0.00001). This difference was significantly more pronounced for P. falciparum (4.40%, 95% CI: 3.95-4.90%, P < 0.00001) compared with P. vivax (1.89%, 95% CI: 1.60-2.22%, P < 0.001) and P. malariae infections (0.22%, 95% CI: 0.13-0.35%, P < 0.0001). The significant proportion of microscopy-negative but PCR-positive individuals (289/7,491, 3.85%) suggest microscopic examination frequently underestimated malaria infections and that active case detection based on microscopy may miss a significant reservoir of infection, especially in low-transmission settings

Cathepsin Z as a novel potential biomarker for osteoporosis

Osteoporosis, one of the most prevalent chronic ageing-related bone diseases, often goes undetected until the first fragility fracture occurs, causing patient suffering and cost to health/social care services. Osteoporosis arises from imbalanced activity of osteoclasts and osteoblasts. Since these cell lineages produce the protease, cathepsin Z, the aim of this study was to investigate whether altered cathepsin Z mRNA levels are associated with osteoporosis in clinical samples. Cathepsin Z mRNA in human peripheral blood mononuclear cells was significantly differentially-expressed among non-osteoporotic controls, osteopenia and osteoporosis patients (p < 0.0001) and in female osteoporosis patients over the age of 50 years (P = 0.0016). Cathepsin Z mRNA level strongly correlated with low bone mineral density (BMD) (g/cm2), lumbar spine L2-L4 and femoral neck (T-scores) (P = 0.0149, 0.0002 and 0.0139, respectively). Importantly, cathepsin Z mRNA was significantly associated with fragility fracture in osteoporosis patients (P = 0.0018). The levels of cathepsin Z mRNA were not significantly higher in patients with chronic inflammatory disorders in these two groups compared to those without (P = 0.774 and 0.666, respectively). ROC analysis showed that cathepsin Z mRNA has strong diagnostic value for osteoporosis and osteoporotic fracture. The results show for the first time that cathepsin Z could be a future diagnostic biomarker for osteoporosis including female osteoporosis patients over the age of 50 years

Hyperhomocysteinemia and Low Folate and Vitamin B12 Are Associated with Vascular Dysfunction and Impaired Nitric Oxide Sensitivity in Morbidly Obese Patients.

There is a high prevalence of hyperhomocysteinemia that has been linked to high cardiovascular risk in obese individuals and could be attributed to poor nutritional status of folate and vitamin B12. We sought to examine the association between blood homocysteine (Hcy) folate, and vitamin B12 levels and vascular dysfunction in morbidly obese adults using novel ex vivo flow-induced dilation (FID) measurements of isolated adipose tissue arterioles. Brachial artery flow-mediated dilation (FMD) was also measured. Subcutaneous and visceral adipose tissue biopsies were obtained from morbidly obese individuals and non-obese controls. Resistance arterioles were isolated in which FID, acetylcholine-induced dilation (AChID), and nitric oxide (NO) production were measured in the absence or presence of the NO synthase inhibitor, L-NAME, Hcy, or the superoxide dismutase mimetic, TEMPOL. Our results demonstrated that plasma Hcy concentrations were significantly higher, while folate, vitamin B12, and NO were significantly lower in obese subjects compared to controls. Hcy concentrations correlated positively with BMI, fat %, and insulin levels but not with folate or vitamin B12. Brachial and arteriolar vasodilation were lower in obese subjects, positively correlated with folate and vitamin B12, and inversely correlated with Hcy. Arteriolar NO measurements and sensitivity to L-NAME were lower in obese subjects compared to controls. Finally, Hcy incubation reduced arteriolar FID and NO sensitivity, an effect that was abolished by TEMPOL. In conclusion, these data suggest that high concentrations of plasma Hcy and low concentrations of folate and vitamin B12 could be independent predictors of vascular dysfunction in morbidly obese individuals

Validation of the Cloud_CCI cloud products in the Arctic

The role of clouds in the Arctic radiation budget is not well understood. Ground-based and airborne measurements provide valuable data to test and improve our understanding. However, the ground-based measurements are intrinsically sparse, and the airborne observations are snapshots in time and space. Passive remote sensing measurements from satellite sensors offer high spatial coverage and an evolving time series, having lengths potentially of decades. However, detecting clouds by passive satellite remote sensing sensors is challenging over the Arctic because of the brightness of snow and ice in the ultraviolet and visible spectral regions, and because of the small brightness temperature contrast to the surface. Consequently, the quality of the resulting cloud data products needs to be assessed quantitatively. In this study, we validate the cloud data products retrieved from the Advanced Very High Resolution Radiometer (AVHRR) post meridiem (PM) data from the polar-orbiting NOAA-19 satellite and compare them with those derived from the ground-based instruments during the sunlit months. The AVHRR cloud data products by the European Space Agency’s (ESA) Cloud Climate Change Initiative (Cloud_CCI) project, which uses the observations in the visible and IR bands to determine cloud properties. The ground-based measurements from four high-latitude sites have been selected for this investigation: Hyytiälä (61.84° N, 24.29° E), North Slope of Alaska (NSA, 71.32° N, 156.61° W), Ny-Alesund (Ny-A, 78.92° N, 11.93° E), and Summit (72.59° N, 38.42° W). The Liquid Water Path (LWP) ground-based data are retrieved from microwave radiometers, while the Cloud Top Height (CTH) has been determined from the integrated lidar-radar measurements. The quality of the satellite products, Cloud Mask and Cloud Optical Depth (COD), have been assessed using data from NSA, whereas LWP and CTH have been investigated over Hyytiälä, NSA, Ny-A, and Summit. The Cloud_CCI COD results for liquid water clouds are in better agreement with the NSA radiometer data than those for ice clouds. For liquid water clouds, the Cloud_CCI COD is underestimated roughly by 2.8 Optical Depth (OD) units. When ice clouds are included, the underestimation increases to about 4.6 OD units. The Cloud_CCI LWP is overestimated over Hyytiälä by 7 gm−2, over NSA by 16 gm−2, and over Ny-Å by 24 gm−2. Over Summit, CCI LWP is overestimated for values lower than 20 gm−2 and underestimated for values greater than 20 gm−2. Overall the results of the CCI LWP retrievals are within the ground-based instrument uncertainties. For CTH retrievals, the Cloud_CCI product overestimates single-layer clouds. To understand the effects of multi layer clouds on the CTH retrievals, the statistics are compared between the single layer clouds and all types (single + multi layer). When the multi layer clouds are included (i.e., all types), the observed CTH overestimation become underestimations of about 360-420 m. The CTH results over Summit station showed the highest biases compared to the other three sites. To understand the scale-dependent differences between the satellite and ground-based data, the Bland-Altman method is applied. This method does not identify any scale-dependent differences for all the selected cloud parameters except for the retrievals over the Summit station. In summary, the Cloud_CCI cloud data products investigated agree reasonably well with those retrieved from ground-based measurements, made at the four high-latitude sites

Sequential ¹⁸F-fluorodeoxyglucose positron emission tomography (¹⁸F-FDG PET) scan findings in patients with extrapulmonary tuberculosis during the course of treatment—a prospective observational study

BACKGROUND: Initial studies of tuberculosis (TB) in macaques and humans using ¹⁸F-FDG positron emission tomography (PET) imaging as a research tool suggest its usefulness in localising disease sites and as a clinical biomarker. Sequential serial scans in patients with extrapulmonary TB (EPTB) could inform on the value of PET-CT for monitoring response to treatment and defining cure. PATIENTS AND METHODS: HIV-negative adults with EPTB from eight sites across six countries had three ¹⁸F-FDG PET/CT scans: (i) within 2 weeks of enrolment, (ii) at 2 months into TB treatment and (iii) at end of ATT treatment. Scanning was performed according to the EANM guidelines. ¹⁸F-FDG PET/CT scans were performed 60 ± 10 min after intravenous injection of 2.5–5.0 MBq/kg of ¹⁸F-FDG. FINDINGS: One hundred and forty-seven patients with EPTB underwent 3 sequential scans. A progressive reduction over time of both the number of active sites and the uptake level (SUVmax) at these sites was seen. At the end of WHO recommended treatment, 53/147 (36.0%) patients had negative PET/CT scans, and 94/147 (63.9%) patients remained PET/CT positive, of which 12 patients had developed MDR TB. One died of brain tuberculoma. INTERPRETATION: Current ⁸F-FDG PET/CT imaging technology cannot be used clinically as a biomarker of treatment response, cure or for decision-making on when to stop EPTB treatment. PET/CT remains a research tool for TB and further development of PET/CT is required using new Mycobacterium tuberculosis-specific radiopharmaceuticals targeting high-density surface epitopes, gene targets or metabolic pathways

PET/CT features of extrapulmonary tuberculosis at first clinical presentation: a cross-sectional observational ¹⁸F-FDG imaging study across six countries

BACKGROUND: A large proportion of the huge global burden of Extrapulmonary tuberculosis (EPTB) are treated empirically without accurate definition of disease sites, and extent of multi-organ disease involvement. Positron emission tomography (PET) imaging using 18F-FDG in TB could be a useful imaging technique for localising disease sites and extent of disease. METHODS: We conducted a study of HIV-negative adult patients with a new clinical diagnosis of EPTB across 8 centres located in 6 countries: India, Pakistan, Thailand, South Africa, Serbia, and Bangladesh to assess the extent of disease and common sites involved at first presentation. 18F-FDG PET/CT scans were performed within 2 weeks of presentation. FINDINGS: A total of 358 patients with EPTB (189 females; 169 males) were recruited over 45 months. Age range 18-83 years (females: median 30 years; males: median 38 years). 350/358 (98%) patients (183 female, 167 male) had positive scan. 118/350 (33.7%) had a single extrapulmonary site and 232/350 (66.3%) had more than one site (organ) affected. Lymph nodes, skeletal, pleura and brain were common sites. 100/358 (28%) of EPTB patients had 18F-FDG PET/CT positive sites in the lung. 110 patients were 18F-FDG PET/CT positive in more body sites than were noted clinically at first presentation and 160 patients had the same number of positive body sites. INTERPRETATION: 18F-FDG PET/CT scan has potential for further elucidating the spectrum of disease, pathogenesis of EPTB, and monitoring the effects of treatment on active lesions over time, and requires longitudinal cohort studies, twinned with biopsy and molecular studies

Validation of the Cloud_CCI (Cloud Climate Change Initiative) cloud products in the Arctic

The role of clouds in the Arctic radiation budget is not well understood. Ground-based and airborne measurements provide valuable data to test and improve our understanding. However, the ground-based measurements are intrinsically sparse, and the airborne observations are snapshots in time and space. Passive remote sensing measurements from satellite sensors offer high spatial coverage and an evolving time series, having lengths potentially of decades. However, detecting clouds by passive satellite remote sensing sensors is challenging over the Arctic because of the brightness of snow and ice in the ultraviolet and visible spectral regions and because of the small brightness temperature contrast to the surface. Consequently, the quality of the resulting cloud data products needs to be assessed quantitatively. In this study, we validate the cloud data products retrieved from the Advanced Very High Resolution Radiometer (AVHRR) post meridiem (PM) data from the polar-orbiting NOAA-19 satellite and compare them with those derived from the ground-based instruments during the sunlit months. The AVHRR cloud data products by the European Space Agency (ESA) Cloud Climate Change Initiative (Cloud_CCI) project uses the observations in the visible and IR bands to determine cloud properties. The ground-based measurements from four high-latitude sites have been selected for this investigation: Hyytiälä (61.84∘ N, 24.29∘ E), North Slope of Alaska (NSA; 71.32∘ N, 156.61∘ W), Ny-Ålesund (Ny-Å; 78.92∘ N, 11.93∘ E), and Summit (72.59∘ N, 38.42∘ W). The liquid water path (LWP) ground-based data are retrieved from microwave radiometers, while the cloud top height (CTH) has been determined from the integrated lidar–radar measurements. The quality of the satellite products, cloud mask and cloud optical depth (COD), has been assessed using data from NSA, whereas LWP and CTH have been investigated over Hyytiälä, NSA, Ny-Å, and Summit. The Cloud_CCI COD results for liquid water clouds are in better agreement with the NSA radiometer data than those for ice clouds. For liquid water clouds, the Cloud_CCI COD is underestimated roughly by 3 optical depth (OD) units. When ice clouds are included, the underestimation increases to about 5 OD units. The Cloud_CCI LWP is overestimated over Hyytiälä by ≈7 g m−2, over NSA by ≈16 g m−2, and over Ny-Å by ≈24 g m−2. Over Summit, CCI LWP is overestimated for values ≤20 g m−2 and underestimated for values &gt;20 g m−2. Overall the results of the CCI LWP retrievals are within the ground-based instrument uncertainties. To understand the effects of multi-layer clouds on the CTH retrievals, the statistics are compared between the single-layer clouds and all types (single-layer + multi-layer). For CTH retrievals, the Cloud_CCI product overestimates the CTH for single-layer clouds. When the multi-layer clouds are included (i.e., all types), the observed CTH overestimation becomes an underestimation of about 360–420 m. The CTH results over Summit station showed the highest biases compared to the other three sites. To understand the scale-dependent differences between the satellite and ground-based data, the Bland–Altman method is applied. This method does not identify any scale-dependent differences for all the selected cloud parameters except for the retrievals over the Summit station. In summary, the Cloud_CCI cloud data products investigated agree reasonably well with those retrieved from ground-based measurements made at the four high-latitude sites.</p

Assessment of the efficacy and toxicity of 131I-metaiodobenzylguanidine therapy for metastatic neuroendocrine tumours

131I-metaiodobenzylguanidine (131I-MIBG) is a licensed palliative treatment for patients with metastatic neuroendocrine tumours. We have retrospectively assessed the consequences of 131I-MIBG therapy in 48 patients (30 gastroenteropancreatic, 6 pulmonary, 12 unknown primary site) with metastatic neuroendocrine tumours attending Royal Liverpool University Hospital between 1996 and 2006. Mean age at diagnosis was 57.6 years (range 34–81). 131I-MIBG was administered on 88 occasions (mean 1.8 treatments, range 1–4). Twenty-nine patients had biochemical markers measured before and after 131I-MIBG, of whom 11 (36.7%) showed >50% reduction in levels post-therapy. Forty patients had radiological investigations performed after 131I-MIBG, of whom 11(27.5%) showed reduction in tumour size post-therapy. Twenty-seven (56.3%) patients reported improved symptoms after 131I-MIBG therapy. Kaplan–Meier analysis showed significantly increased survival (P=0.01) from the date of first 131I-MIBG in patients who reported symptomatic benefit from therapy. Patients with biochemical and radiological responses did not show any statistically significant alteration in survival compared to non-responders. Eleven (22.9%) patients required hospitalisation as a consequence of complications, mostly due to mild bone marrow suppression. 131I-MIBG therefore improved symptoms in more than half of the patients with metastatic neuroendocrine tumours and survival was increased in those patients who reported a symptomatic response to therapy

Genetic and metabolic predictors of chemosensitivity in oligodendroglial neoplasms

The −1p/−19q genotype predicts chemosensitivity in oligodendroglial neoplasms, but some with intact 1p/19q also respond and not all with 1p/19q loss derive durable benefit from chemotherapy. We have evaluated the predictive and prognostic significance of pretherapy 201Tl and 18F-FDG SPECT and genotype in 38 primary and 10 recurrent oligodendroglial neoplasms following PCV chemotherapy. 1p/19q loss was seen in 8/15 OII, 6/15 OAII, 7/7 OIII, 3/11 OAIII and was associated with response (Fisher-Exact: P=0.000) and prolonged progression-free (log-rank: P=0.002) and overall survival (OS) (log-rank: P=0.0048). Response was unrelated to metabolism, with tumours with high or low metabolism showing response. Increased 18F-FDG or 201Tl uptake predicted shorter progression-free survival (PFS) in the series (log-rank: 201Tl P=0.0097, 18F-FDG P=0.0170) and in cases with or without the −1p/−19q genotype. Elevated metabolism was associated with shorter OS in cases with intact 1p/19q (log-rank: 18F-FDG P=0.0077; 201Tl P=0.0004) and shorter PFS in responders (log-rank: 18F-FDG P=0.005; 201Tl P=0.0132). 201Tl uptake and 1p/19q loss were independent predictors of survival in multivariate analysis. In this initial study, 201Tl and 18F-FDG uptake did not predict response to PCV, but may be associated with poor survival following therapy irrespective of genotype. This may be clinically useful warranting further study