Computed tomography-derived fractional flow reserve (FFRCT) has no additional clinical impact over the anatomical Coronary Artery Disease - Reporting and Data System (CAD-RADS) in real-world elective healthcare of coronary artery disease.

AIM: To evaluate the impact of computed tomography-derived fractional flow reserve (FFRCT) compared to the anatomical Coronary Artery Disease - Reporting and Data System (CAD-RADS) in the elective assessment of coronary artery disease in real-world cardiology practise. MATERIALS AND METHODS: A retrospective review was undertaken of 1,239 coronary CT examinations from August 2018 to December 2019 with a minimum follow-up period of 1 year. Coronary disease was classified according to the CAD-RADS system. A non-occlusive ≥30% maximum diameter stenosis was considered eligible for FFRCT. Lesion-specific FFRCT and FFR were considered positive if ≤ 0.80. The patients were followed up using the hospital radiology information system and the electronic patient record. A positive outcome was defined by a subsequent invasive angiogram (ICA) showing disease requiring revascularisation or FFR ≤0.80 or a positive stress test or medical therapy for angina in CAD-RADS 4. RESULTS: Of the 1,145 analysable studies (mean follow up 618 ± 153 days) the incidence of a positive result was 7% with a 5.4% elective revascularisation rate. Two hundred and forty-five patients (CAD-RADS 2-4) had FFRCT. FFRCT reduced the accuracy of the CAD-RADS grade from 91% to 78.4% (p<0.001). In CAD-RADS 2, the accuracy is reduced from 99% to 90.7% (p=0.005), and in CAD-RADS 3 from 93.9% to 67.7% (p<0.001). In CAD-RADS 4, FFRCT increases accuracy from 69.4% to 75.5% (p=0.025), but 89.8% of FFRCT are positive and specificity is low (26.7%). CONCLUSION: In the present "real-world" practise, FFRCT does not improve standard radiological assessment of coronary disease graded by the CAD-RADS alone.

Older men who sustain a hip fracture experience greater declines in bone mineral density at the contralateral hip than non-fractured comparators.

Men experience declining bone mineral density (BMD) after hip fracture; however, changes attributable to fracture are unknown. This study evaluated the excess BMD decline attributable to hip fracture among older men. Older men with hip fracture experienced accelerated BMD declines and are at an increased risk of secondary fractures. INTRODUCTION: The objective was to determine whether bone mineral density (BMD) changes in men after hip fracture exceed that expected with aging. METHODS: Two cohorts were used: Baltimore Hip Studies 7th cohort (BHS-7) and Baltimore Men's Osteoporosis Study (MOST). BHS-7 recruited older adults (N = 339) hospitalized for hip fracture; assessments occurred within 22 days of admission and at 2, 6, and 12 months follow-up. MOST enrolled age-eligible men (N = 694) from population-based listings; data were collected at a baseline visit and a second visit that occurred between 10 and 31 months later. The combined sample (n = 452) consisted of Caucasian men from BHS-7 (n = 89) and MOST (n = 363) with ≥ 2 dual-energy X-ray absorptiometry scans and overlapping ranges of age, height, and weight. Mixed-effect models estimated rates of BMD change, and generalized linear models evaluated differences in annual bone loss at the total hip and femoral neck between cohorts. RESULTS: Adjusted changes in total hip and femoral neck BMD were - 4.16% (95% CI, - 4.87 to - 3.46%) and - 4.90% (95% CI, - 5.88 to - 3.92%) in BHS-7 participants; - 1.57% (95% CI, - 2.19 to - 0.96%) and - 0.99% (95% CI, - 1.88 to - 0.10%) in MOST participants; and statistically significant (P < 0.001) between-group differences in change were - 2.59% (95% CI, - 3.26 to - 1.91%) and - 3.91% (95% CI, - 4.83 to - 2.98%), respectively. CONCLUSION: Hip fracture in older men is associated with accelerated BMD declines at the non-fractured hip that are greater than those expected during aging, and pharmacological interventions in this population to prevent secondary fractures may be warranted.

Dynamics of habitat selection in birds: adaptive response to nest predation depends on multiple factors.

According to theory, habitat selection by organisms should reflect underlying habitat-specific fitness consequences and, in birds, reproductive success has a strong impact on population growth in many species. Understanding processes affecting habitat selection also is critically important for guiding conservation initiatives. Northern pintails (Anas acuta) are migratory, temperate-nesting birds that breed in greatest concentrations in the prairies of North America and their population remains below conservation goals. Habitat loss and changing land use practices may have decoupled formerly reliable fitness cues with respect to nest habitat choices. We used data from 62 waterfowl nesting study sites across prairie Canada (1997-2009) to examine nest survival, a primary fitness metric, at multiple scales, in combination with estimates of habitat selection (i.e., nests versus random points), to test for evidence of adaptive habitat choices. We used the same habitat covariates in both analyses. Pintail nest survival varied with nest initiation date, nest habitat, pintail breeding pair density, landscape composition and annual moisture. Selection of nesting habitat reflected patterns in nest survival in some cases, indicating adaptive selection, but strength of habitat selection varied seasonally and depended on population density and landscape composition. Adaptive selection was most evident late in the breeding season, at low breeding densities and in cropland-dominated landscapes. Strikingly, at high breeding density, habitat choice appears to become maladaptive relative to nest predation. At larger spatial scales, the relative availability of habitats with low versus high nest survival, and changing land use practices, may limit the reproductive potential of pintails.

Survey of UK imaging practice for the investigation of pulmonary embolism in pregnancy.

AIM: To determine the utilisation of computed tomography pulmonary angiography (CTPA) and lung scintigraphy in the UK, and to assess their diagnostic qualities in the investigation of suspected pulmonary embolism (PE) in pregnancy. MATERIALS AND METHODS: Data were collected via electronic questionnaire in the UK from 24 sites. Data on the choice of imaging technique, radiation dose, technical adequacy, weeks' gestation, presenting symptoms, and further management of patients with indeterminate imaging were collected. RESULTS: The sample represented a population of 15.5 million and showed wide variation in the probability of investigation of suspected PE with rates per live birth of 0.06-2.2%. Nine hundred and ninety-one patients were imaged and there were 48 positive scans, an incidence of 0.038%. Of the 269 CTPAs performed, 5.9% were positive, 8.9% were technically inadequate. Of the 769 scintigraphy scans performed, 3.8% were positive and 9.1% were indeterminate; 63% of positive scans were in the third trimester. Most inadequate/indeterminate scans were in the third trimester. The calculated typical radiation dose to the breast and fetus from CTPA ranged from 14 to 2 mGy and 0.02 to 0.002mGy, respectively, and approximately 0.28 and 0.2 mGy, respectively, from scintigraphy. CONCLUSION: The incidence of PE in this population was extremely low and the number of indeterminate or inadequate scans was comparable. This suggests choice of imaging should be made based upon availability and radiation exposure.

Extracellular and cellular Hsp72 differ as biomarkers in acute exercise/environmental stress and recovery.

Stress-inducible Hsp72 is a potential biomarker to track risk of exertional heat illness during exercise/environmental stress. Characterization of extracellular (eHsp72) vs cellular Hsp72 (iHsp72) responses is required to define the appropriate use of Hsp72 as a reliable biomarker. In each of four repeat visits, participants (n = 6 men, 4 trials; total n = 24): (a) passively dehydrated overnight, (b) exercised (2 h) with no fluid in a hot, humid environmental chamber, (c) rested and rehydrated (1 h), (d) maximally exercised for 0.5 h, and (e) returned after 24 h of at-home recovery and rehydration. We measured rectal temperature, hydration status (% body mass loss, urine markers, serum osmolality), and Hsp72 (ELISA, flow cytometry. eHsp72 (circulating) and iHsp72 (CD3+ PBMCs) correlated (P < 0.05) with markers of heat, exercise, and dehydration stresses. eHsp72 immediately post-exercise (>15% above baseline, P < 0.05) decreased back to baseline levels by 1 h post-exercise, but iHsp72 expression continued to rise and remained elevated 24 h post-exercise (~2.5-fold baseline, P < 0.05). These data suggest that in addition to the classic physiological biomarkers of exercise heat stress, using cellular Hsp72 as an indicator of lasting effects of stress into recovery may be most appropriate for determining long-term effects of stress on risk for exertional heat illness.

Application of TWIST MR angiography to aid successful central venous access in challenging patients: initial single-centre experience.

AIM: To investigate whether time-resolved angiography with interleaved stochastic trajectories (TWIST) with GeneRalised Autocalibrating Partially Parallel Acquisitions (GRAPPA) parallel acquisition could be used successfully to non-invasively and efficiently image patients with more complex vascular access issues. MATERIALS AND METHODS: TWIST magnetic resonance angiography (MRA) in the GRAPPA algorithm was performed on 15 patients at our centre using the 1.5 T Siemens Magnetom Avanto MRI system. Images were interpreted by cardiac radiologists. RESULTS: TWIST provided excellent dynamic imaging of the venous system, demonstrating venous occlusion, stenoses, and collaterals, as well as providing good anatomical detail. CONCLUSION: TWIST MRA enables successful identification of candidate sites for central/tunnelled line access, whilst diagnosing complications of long-term access such as venous thrombosis or congenital venous anomalies.

Assessing Hydration in Children: From Science to Practice.

Raising children's awareness about their hydration status could be done through a noninvasive biomarker. Urine color (UC) has been validated as a biomarker of hydration in adults and children aged 8-14 years. The aim of this survey was to design and to evaluate the level of understanding and attractiveness of a self-assessment, UC-based hydration tool for children aged 6-11 years. The first phase of the survey consisted of face-to-face interviews during which 84 children identified those graphical elements necessary to understand the hydration message from 6 illustration-based designs containing the UC chart. The graphic elements selected were the basis to create 3 new designs. During the 2nd phase, the level of understanding and attractiveness of these 3 new designs was then evaluated via an online questionnaire by a total of 1,231 children in 3 countries. The design with the highest level of understanding was totally or partially understood by 76% of the participants, independent of age and gender. The levels of understanding, however, differed in the countries. In Indonesia, the levels of understanding of the 3 designs were comparable; whereas in both France (74%) and Mexico (78%), significantly more participants totally and partially understood one of the 3 designs. The levels of attractiveness of the 3 designs were comparable, independent of country, age, and gender. On average, 80% of all participants liked the 3 designs a bit or a lot. Only 14% did not like the designs, and 5% of participants had no opinion regarding attractiveness. These results indicated that three out of four children like and understand the correct hydration message from a strictly illustration-based tool containing the eight-point UC scale.

AIMP1 deficiency presents as a cortical neurodegenerative disease with infantile onset.

We report the second family with AIMP1 deficiency, due to a homozygous truncating AIMP1 (g.107248613 C > T) mutation. This female showed early-onset developmental arrest, intractable epileptic spasms, microcephaly, and a rapid clinical course leading to premature death, associated with cerebral atrophy and myelin deficiency on brain MRI. Clinical and neuroimaging findings are consistent with a primary neuronal degenerative disorder, rather than with the previously reported Perlizaeus-Merzbacher-like phenotype. Given its critical role in neurofilament assembly 16, impaired myelin formation is due to neuronal/axonal dysfunction. We propose that AIMP1 deficiency be added to the differential diagnosis of infantile onset, progressive neurodegenerative disease.

Primary carbonatite melt from deeply subducted oceanic crust.

Partial melting in the Earth's mantle plays an important part in generating the geochemical and isotopic diversity observed in volcanic rocks at the surface. Identifying the composition of these primary melts in the mantle is crucial for establishing links between mantle geochemical 'reservoirs' and fundamental geodynamic processes. Mineral inclusions in natural diamonds have provided a unique window into such deep mantle processes. Here we provide experimental and geochemical evidence that silicate mineral inclusions in diamonds from Juina, Brazil, crystallized from primary and evolved carbonatite melts in the mantle transition zone and deep upper mantle. The incompatible trace element abundances calculated for a melt coexisting with a calcium-titanium-silicate perovskite inclusion indicate deep melting of carbonated oceanic crust, probably at transition-zone depths. Further to perovskite, calcic-majorite garnet inclusions record crystallization in the deep upper mantle from an evolved melt that closely resembles estimates of primitive carbonatite on the basis of volcanic rocks. Small-degree melts of subducted crust can be viewed as agents of chemical mass-transfer in the upper mantle and transition zone, leaving a chemical imprint of ocean crust that can possibly endure for billions of years.

Temporal drivers of tryptophan-like fluorescent dissolved organic matter along a river continuum.

Tryptophan-like fluorescence (TLF) is used to indicate anthropogenic inputs of dissolved organic matter (DOM), typically from wastewater, in rivers. We hypothesised that other sources of DOM, such as groundwater and planktonic microbial biomass can also be important drivers of riverine TLF dynamics. We sampled 19 contrasting sites of the River Thames, UK, and its tributaries. Multivariate mixed linear models were developed for each site using 15 months of weekly water quality observations and with predictor variables selected according to the statistical significance of their linear relationship with TLF following a stepwise procedure. The variables considered for inclusion in the models were potassium (wastewater indicator), nitrate (groundwater indicator), chlorophyll-a (phytoplankton biomass), and Total bacterial Cells Counts (TCC) by flow cytometry. The wastewater indicator was included in the model of TLF at 89 % of sites. Groundwater was included in 53 % of models, particularly those with higher baseflow indices (0.50-0.86). At these sites, groundwater acted as a negative control on TLF, diluting other potential sources. Additionally, TCC was included positively in the models of six (32 %) sites. The models on the Thames itself using TCC were more rural sites with lower sewage inputs. Phytoplankton biomass (Chlorophyll-a) was only used in two (11 %) site models, despite the seasonal phytoplankton blooms. It is also notable that, the wastewater indicator did not always have the strongest evidence for inclusion in the models. For example, there was stronger evidence for the inclusion of groundwater and TCC than wastewater in 32 % and 5 % of catchments, respectively. Our study underscores the complex interplay of wastewater, groundwater, and planktonic microbes, driving riverine TLF dynamics, with their influence determined by site characteristics.

Multi-scale habitat selection affects offspring survival in a precocial species.

In theory, habitat preferences should be adaptive. Accordingly, fitness is often assumed to be greater in preferred habitats; however, this assumption is rarely tested and, when it is, the results are often equivocal. Habitat preferences may not directly convey fitness advantages if animals are constrained by tradeoffs with other selective pressures like predation or food availability. We address unresolved questions about the survival consequences of habitat choices made during brood-rearing in a precocial species with exclusive maternal care (mallard Anas platyrhynchos, n = 582 radio-marked females on 27 sites over 8 years). We directly linked duckling survival with habitat selection patterns at two spatial scales using logistic regression and model selection techniques. At the landscape scale (55-80 km(2)), females that demonstrated stronger selection of areas with more cover type 4 wetlands and greater total cover type 3 wetland area (wetlands with large expanses of open water surrounded by either a narrow or wide peripheral band of vegetation, respectively) had lower duckling survival rates than did females that demonstrated weaker selection of these habitats. At finer scales (0.32-7.16 km(2)), females selected brood-rearing areas with a greater proportion of wetland habitat with no consequences for duckling survival. However, females that avoided woody perennial habitats composed of trees and shrubs fledged more ducklings. The relationship between habitat selection and survival depended on both spatial scale and habitats considered. Females did not consistently select brood-rearing habitats that conferred the greatest benefits, an unexpected finding, although one that has also been reported in other recent studies of breeding birds.

A Single Dose of Ibuprofen Impacts IL-10 Response to 164-km Road Cycling in the Heat.

Purpose: The purpose was to determine the effect of a single-dose prophylactic ibuprofen use before a 164-km road cycling event in high ambient temperature on the circulating cytokine and leukocyte responses. Methods: Twenty-three men (53 ± 8 y, 172.0 ± 22.0 cm, 85.1 ± 12.8 kg, 19.6 ± 4.4% body fat) completed a 164-km self-paced recreational road cycling event in a hot, humid, sunny environment (WBGT = 29.0 ± 2.9°C) after consuming 600 mg of ibuprofen (n = 13) or a placebo (n = 10). Blood samples were obtained one to two hours before (PRE) and immediately after (POST) the event, and analyzed for concentrations of circulating cytokines interleukins (IL)-1ß, IL-2, IL-4, IL-5, IL-6, IL-7, IL-8, IL-10, IL-12, IL-13, GM-CSF, IFN-γ, and TNF-α and leukocytes (total leukocytes, granulocytes, monocytes, and lymphocytes). Results: Event completion time was 400.2 ± 74.8 min. Concentrations of all cytokines (except IL-1ß, IL-2, IL-5, IL-12, GM-CSF, and IFN-γ) and of all leukocyte subsets increased from PRE to POST. Ibuprofen ingestion attenuated the increase in IL-10 (86% increase with Ibuprofen; 270% increase with placebo). Conclusions: Consuming 600 mg of Ibuprofen prior to a 164-km road cycling event in a hot-humid environment attenuates exercise-induced increases in the concentration of the anti-inflammatory cytokine IL-10, but does not alter the effect of the exercise event on concentrations of other circulating cytokines or leukocyte subset concentrations.

Genetic analysis of vertebral trabecular bone density and cross-sectional area in older men.

We investigated 383 bone candidate genes for associations between single nucleotide polymorphisms and vertebral trabecular volumetric bone mineral density (vBMD) and cross-sectional area (CSA) in 2,018 Caucasian men aged ≥ 65 years. SNPs in TGFBR3, SOST, KL, CALCR, LEP, CSF1R, PTN, GNRH2, FGFR2, and MEPE were associated with vBMD and SNPs in CYP11B1, DVL2, DLX5, WNT4, and PAX7 were associated with CSA in independent study samples (p < 0.005). INRODUCTION: Vertebral bone mineral density and cross-sectional area are important determinants of vertebral bone strength. Little is known about the specific genetic variants that influence these phenotypes in humans. METHODS: We investigated the potential genetic variants associated with vertebral trabecular volumetric BMD and CSA measured by quantitative computed tomography. We initially tested for association between these phenotypes and 4608 tagging and potentially functional single nucleotide polymorphisms (SNPs) in 383 candidate genes in 862 community-dwelling Caucasian men aged ≥ 65 years in the Osteoporotic Fractures in Men Study. RESULTS: SNP associations were then validated by genotyping an additional 1,156 randomly sampled men from the same cohort. We identified 11 SNPs in 10 genes (TGFBR3, SOST, KL, CALCR, LEP, CSF1R, PTN, GNRH2, FGFR2, and MEPE) that were consistently associated with trabecular vBMD and five SNPs in five genes (CYP11B1, DVL2, DLX5, WNT4, and PAX7) that were consistently associated with CSA in both samples (p < 0.005). CONCLUSION: None of the SNPs associated with trabecular vBMD were associated with CSA. Our findings raise the possibility that at least some of the loci for vertebral trabecular BMD and bone size may be distinct.

Association analysis of 33 lipoprotein candidate genes in multi-generational families of African ancestry.

African ancestry individuals have a more favorable lipoprotein profile than Caucasians, although the mechanisms for these differences remain unclear. We measured fasting serum lipoproteins and genotyped 768 tagging or potentially functional single nucleotide polymorphisms (SNPs) across 33 candidate gene regions in 401 Afro-Caribbeans older than 18 years belonging to 7 multi-generational pedigrees (mean family size 51, range 21-113, 3,426 relative pairs). All lipoproteins were significantly heritable (P<0.05). Gender-specific analysis showed that heritability for triglycerides was much higher (P<0.01) in women than in men (women, 0.62+/-0.18, P<0.01; men, 0.13+/-0.17, P>0.10), but the heritability for LDL cholesterol (LDL-C) was higher (P<0.05) in men than in women (men, 0.79+/-0.21, P<0.01; women, 0.39+/-0.12, P<0.01). The top 14 SNPs that passed the false discovery rate threshold in the families were then tested for replication in an independent population-based sample of 1,750 Afro-Caribbean men aged 40+ years. Our results revealed significant associations for three SNPs in two genes (rs5929 and rs6511720 in LDLR and rs7517090 in PCSK9) and LDL-C in both the family study and in the replication study. Our findings suggest that LDLR and PCSK9 variants may contribute to a variation in LDL-C among African ancestry individuals. Future sequencing and functional studies of these loci may advance our understanding of genetic factors contributing to LDL-C in African ancestry populations.

Adenoid cystic carcinoma of the palate with isolated cutaneous metastasis: a unique case and review of current and future treatment modalities of metastatic disease.

Adenoid cystic carcinoma (ACC) is an aggressive salivary gland neoplasm characterized by high rates of local recurrence, early metastasis, and a poor long-term prognosis. Approximately 20-50% of cases result in distant metastasis, commonly involving the lung, bone, liver, and brain. Cutaneous metastasis is a rare occurrence, with a small number of cases reported previously in the context of multiple metastatic sites of involvement. We present a unique case of ACC of the hard palate with isolated cutaneous metastasis. A 36-year-old woman underwent a subtotal maxillectomy and skull base resection for the treatment of a T4N0 ACC of the right maxilla. One year postoperatively, the patient presented with multiple rapidly growing painful nodules on the skin of the scalp, neck, and chest. Biopsy confirmed metastatic poorly differentiated ACC, and positron emission tomography demonstrated cutaneous metastatic lesions without evidence of other tissue involvement. This case highlights the possible rare and aggressive pathways of metastasis of ACC. Currently there is no consensus for the treatment of disseminated disease, due to the poor efficacy of current treatment modalities. Where isolated metastasis is present, surgical resection can be attempted to control disease progression; however the benefit of metastasectomy on survival is not substantiated. As such, the role of newer targeted systemic therapies needs to be further investigated in the hope of achieving disease control.

Tumour necrosis factor-alpha processing in interstitial lung disease: a potential role for exogenous proteinase-3.

Tumour necrosis factor (TNF) blockade has become an important immunomodulatory therapy, particularly in patients refractory to conventional immunosuppression, but responses can be unpredictable. Understanding the complex biology of TNF processing may be key to predicting such responses and reduce unwanted side effects. TNF bioavailability is regulated partly by TNF-alpha converting enzyme (TACE) cleavage; however, it can also be cleaved by proteinase-3 (PR-3). We have demonstrated this mechanism previously in healthy human alveolar macrophages (AM), leading us to hypothesize that PR-3-mediated TNF processing may be an important mechanism in inflammatory lung disease. Furthermore, this may be more apparent in diseases with a neutrophil component typical of usual interstitial pneumonia (UIP), compared with sarcoidosis, where lymphocytes predominate. We isolated AM from patients with UIP and sarcoidosis and healthy subjects. We found increased TACE expression on AM in sarcoidosis. In contrast, TACE was not increased in UIP; we found increased cleavage of glutathione S-transferase-proTNF) substrate, relative to both sarcoidosis and healthy controls. Furthermore, cleavage was subject to inhibition by serine protease inhibitor, rather than a TACE inhibitor BB-3103. Cleavage was proportional to the number of neutrophils isolated from bronchoalveolar lavage, whereas there was an inverse relationship between neutrophils and BB-3103 inhibition. There was also increased PR-3 on the AM surface in UIP relative to healthy controls. These data provide evidence for PR-3-mediated cleavage in UIP, which may have implications for future therapeutic targeting of TACE.

Changes in tuberculosis epidemiology, United States, 1993-2017.

BACKGROUND: After 20 years of steady decline, the pace of decline of tuberculosis (TB) incidence in the United States has slowed.METHODS: Trends in TB incidence rates and case counts since 1993 were assessed using national US surveillance data. Patient characteristics reported during 2014-2017 were compared with those for 2010-2013.RESULTS: TB rates and case counts slowed to an annual decline of respectively 2.2% (95%CI -3.4 to -1.0) and 1.5% (95%CI -2.7 to -0.3) since 2012, with decreases among US-born persons and no change among non-US-born persons. Overall, persons with TB diagnosed during 2014-2017 were older, more likely to have combined pulmonary and extra-pulmonary disease than extra-pulmonary disease alone, more likely to be of non-White race, and less likely to have human immunodeficiency virus infection, or cavitary pulmonary disease. During 2014-2017, non-US-born persons with TB were more likely to have diabetes mellitus, while the US-born were more likely to have smear-positive TB and use non-injecting drugs.CONCLUSION: Changes in epidemiologic trends are likely to affect TB incidence in the coming decades. The Centers for Disease Control and Prevention has called for increased attention to TB prevention through the detection and treatment of latent tuberculous infection.

Using dissolved organic matter fluorescence to identify the provenance of nutrients in a lowland catchment; the River Thames, England.

Catchment based solutions are being sought to mitigate water quality pressures and achieve multiple benefits but their success depends on a sound understanding of catchment functioning. Novel approaches to monitoring and data analysis are urgently needed. In this paper we explore the potential of river water fluorescence at the catchment scale in understanding nutrient concentrations, sources and pathways. Data were collected from across the River Thames basin from January 2012 to March 2015. Analysing emission excitation matrices (EEMs) using both PARAFAC and optimal area averaging produced consistent results for humic-like component 1 and tryptophan-like component 4 in the absence of a subset of samples that exhibited an unusual peak; illustrating the importance of inspecting the entire EEM before using peak averaging methods. Strong relationships between fluorescence components and dissolved organic carbon (DOC), soluble reactive phosphorus (SRP), and ammonium clearly demonstrated its potential, in this study basin, as a field based surrogate for nutrients. Analysing relationships between fluorescence, catchment characteristics and boron from across the basin enabled new insights into the provenance of nutrients. These include evidence for diffuse sources of DOC from near surface hydrological pathways (i.e. soil horizons); point source inputs of nutrients from sewage effluent discharges; and diffuse contributions of nutrients from agriculture and/or sewage (e.g. septic tanks). The information gained by broad scale catchment wide monitoring of fluorescence could support catchment managers in (a) prioritising subcatchments for nutrient mitigation; (b) providing information on relative nutrient source contributions; and (c) providing evidence of the effectiveness of investment in pollution mitigation measures. The collection of high resolution fluorescence data at the catchment scale and, in particular, over shorter event timescales would complement broad scale assessments by enhancing our hydro-biogeochemical process understanding.

TOM22, a core component of the mitochondria outer membrane protein translocation pore, is a mitochondrial receptor for the proapoptotic protein Bax.

The association of Bax with mitochondria is an essential step in the implementation of apoptosis. By using a bacterial two-hybrid assay and crosslinking strategies, we have identified TOM22, a component of the translocase of the outer mitochondrial membrane (TOM), as a mitochondrial receptor of Bax. Peptide mapping showed that the interaction of Bax with TOM22 involved the first alpha helix of Bax and possibly two central alpha helices, which are homologous to the pore forming domains of some toxins. Antibodies directed against TOM22 or an antisense knockdown of the expression of TOM22 specifically inhibited the association of Bax with mitochondria and prevented Bax-dependent apoptosis. In yeast, a haploid strain for TOM22 exhibited a decreased expression of TOM22 and mitochondrial association of ectopically expressed human Bax. Our data provide a new perspective on the mechanism of association of Bax with mitochondria as it involves a classical import pathway.