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The CARIACO Ocean Time Series program has made monthly measurements of oxygen, nutrients, and carbon system parameters (∑CO2, alkalinity, pH) in the Cariaco Basin since 1996. At the same time, sediment traps have collected settling particles at four to five depths ranging from 150 to 1,200 m. The depth of the transition from oxic to anoxic conditions has fluctuated dramatically over the time series due to changes in the occurrence of Caribbean water intrusions into the deep basin. Nutrient concentrations in the deep basin have increased steadily with time in a proportion reflective of the elemental ratios in the settling organic matter, although N:P ratios in the water column (approximately 16:1) differ from ratios in the accumulating nutrients (11:1) and the settling flux (ranging between 5:1 and 12.5:1). This difference is likely due to changes in the source material for remineralization, either because of sizeable ecosystem changes or changes in the relative importance of the terrestrial input of inorganic P or scavenging of P by mineral precipitation near the oxic/anoxic interface. Alternatively, there may have been changes in the degree of preferential remineralization of P.

Using the structural and electronic tunability of molecules to control magnetism is a central challenge of inorganic chemistry. Herein, a ten-member family of the high-ordering temperature (Tc) molecule-based magnetic coordination networks of the form V[x-ClnPTCE]2·yCH2Cl2 (PTCE = phenyltricyanoethylene, y < 0.5) were synthesized and characterized, where x is (are) the position(s) and n is the number of chlorine substitutions on the phenyl ring. These chlorophenyltricyanoethelenes are tunable analogs of the more commonly investigated tetracyanoethylene (TCNE). Varying the number and position of chlorine substitution around the phenyl ring engendered a family of network solids with significantly different magnetic ordering temperatures ranging from 146 to 285 K. The Tcs of these ferrimagnets were rationalized with the aid of cyclic voltammetry and Density Functional Theory (DFT) calculations.

A consistent set of measurement techniques must be applied to reliably and reproducibly evaluate the efficacy of treatments for cutaneous neurofibromas (cNFs) in people with neurofibromatosis type 1 (NF1). cNFs are neurocutaneous tumors that are the most common tumor in people with NF1 and represent an area of unmet clinical need. This review presents the available data regarding approaches in use or development to identify, measure, and track cNFs, including calipers, digital imaging, and high-frequency ultrasound sonography. We also describe emerging technologies such as spatial frequency domain imaging and the application of imaging modalities such as optical coherence tomography that may enable the detection of early cNFs and prevention of tumor-associated morbidity.

Introduction to Volume 8: Harbour seals in the North Atlantic and the Baltic

We conducted a review of the literature and unpublished databases to describe the distribution, abundance, ecology and status of harbour seals (Phoca vitulina concolor) in U.S. Atlantic waters. The harbour seal is the most abundant and widespread seal species in this area. Since passage of the U.S. Marine Mammal Protection Act of 1972, the number of harbour seals observed during the pupping season in this region has increased from about 10,500 animals in 1981 to 38,000 animals in 2001 (uncorrected counts), an average annual rate of 6.6%. This increase has beenrelatively consistent over the 20 years, and there is no indication that the population size has stabilized. Correspondingly, the seasonal distribution has expanded and interactions between seals and anthropogenic activities have increased.

We demonstrate a motion-resistant, three-wavelength, spatial frequency domain imaging (SFDI) system with ambient light suppression using a new 8-tap CMOS image sensor developed in our laboratory. Compared to the previous sensor (134×150), the new sensor’s readout maximum frame rate has improved to 33fps from 6.28fps, and the new 700×540-pixel sensor allows imaging at a higher spatial resolution over a larger field of view. Furthermore, the number of projected images needed per wavelength is reduced from three to two after applying the Hilbert transform. One image of planar illumination and one image for sinusoidal pattern projection at three wavelengths as well as one image of ambient light are captured by the 8-tap image sensor concurrently. The bias caused by ambient light is removed by subtracting the ambient light image from other images. Suppression of motion artifacts is achieved by reducing the exposure and projection time of each pattern. Sufficient signal level is maintained by repeating the exposure multiple times. In this study, LEDs with wavelengths of 554nm, 660nm, and 730nm were used to estimate oxy-/deoxyhemoglobin and melanin concentrations from in-vivo volar forearm skin.

BACKGROUND: Patients with chronic obstructive pulmonary disease (COPD) who smoke have a greater annual rate of decline in forced expiratory volume in 1 s (FEV1) than those patients who have stopped smoking.

BACKGROUND: There is increasing interest in health care resource use (HRU) in Canada, particularly in resources associated with acute exacerbations of chronic obstructive pulmonary disease (COPD).

Depression is common, especially in women of child-bearing age; prevalence estimates for this group range from 8% to 12%, and there is robust evidence that maternal depression is associated with mental health problems in offspring. Suicidal behaviour is a growing concern amongst young people and those exposed to maternal depression are likely to be especially at high risk. The aim of this study was to utilise a large, prospective population cohort to examine the relationship between depression symptom trajectories in mothers over the first eleven years of their child's life and subsequent adolescent suicidal ideation. An additional aim was to test if associations were explained by maternal suicide attempt and offspring depressive disorder. Data were utilised from a population-based birth cohort: the Avon Longitudinal Study of Parents and Children. Maternal depression symptoms were assessed repeatedly from pregnancy to child age 11 years. Offspring suicidal ideation was assessed at age 16 years. Using multiple imputation, data for 10,559 families were analysed. Using latent class growth analysis, five distinct classes of maternal depression symptoms were identified (minimal, mild, increasing, sub-threshold, chronic-severe). The prevalence of past-year suicidal ideation at age 16 years was 15% (95% CI: 14-17%). Compared to offspring of mothers with minimal symptoms, the greatest risk of suicidal ideation was found for offspring of mothers with chronic-severe symptoms [OR 3.04 (95% CI 2.19, 4.21)], with evidence for smaller increases in risk of suicidal ideation in offspring of mothers with sub-threshold, increasing and mild symptoms. These associations were not fully accounted for by maternal suicide attempt or offspring depression diagnosis. Twenty-six percent of non-depressed offspring of mothers with chronic-severe depression symptoms reported suicidal ideation. Risk for suicidal ideation should be considered in young people whose mothers have a history of sustained high levels of depression symptoms, even when the offspring themselves do not have a depression diagnosis.

Contactins and Contactin-Associated Proteins, and Contactin-Associated Protein-Like 2 (CNTNAP2) in particular, have been widely cited as autism risk genes based on findings from homozygosity mapping, molecular cytogenetics, copy number variation analyses, and both common and rare single nucleotide association studies. However, data specifically with regard to the contribution of heterozygous single nucleotide variants (SNVs) have been inconsistent. In an effort to clarify the role of rare point mutations in CNTNAP2 and related gene families, we have conducted targeted next-generation sequencing and evaluated existing sequence data in cohorts totaling 2704 cases and 2747 controls. We find no evidence for statistically significant association of rare heterozygous mutations in any of the CNTN or CNTNAP genes, including CNTNAP2, placing marked limits on the scale of their plausible contribution to risk.

Until recently, multiple sclerosis has been viewed as an entirely inflammatory disease without acknowledgment of the significant neurodegenerative component responsible for disease progression and disability. This perspective is being challenged by observations of a dissociation between inflammation and neurodegeneration where the neurodegenerative component may play a more significant role in disease progression. In this review, we explore the relationship between mitochondrial dysfunction and neurodegeneration in multiple sclerosis. We review evidence that the ketogenic diet can improve mitochondrial function and discuss the potential of the ketogenic diet in treating progressive multiple sclerosis for which no treatment currently exists.

A decade-long study of the Cariaco Basin has demonstrated that the suboxic interface in this system is temporally and spatially variable and that it is the home for a diverse and active microbial community. The thickness and structure of the suboxic zone appears to be primarily controlled by the physics of the basin, with oxygen containing intrusions occurring from both eastern and western sills. The microbial populations, which include both heterotrophic and chemoautotrophic micro-organisms, are actively growing at rates which cannot be supported by vertical transport of oxidants or reductants. Our studies suggest that the microbial loop depends on cycling of intermediate oxidation state sulfur species (sulfite, thiosulfate and elemental S) possibly coupled with cycling of metal oxides. Production of these species is maintained by the active intrusion process and by transport from land of iron and metal oxides during rain events.Los estudios realizados en la Fosa de Cariaco durante una década han demostrado que la interfaz sub-óxica en este sistema posee una variabilidad temporal y espacial, siendo el hábitat de una comunidad microbiana diversa y activa. La circulación en la cuenca, caracterizada por intrusiones ricas en oxígeno desde los umbrales oriental y occidental, controla aparentemente el espesor y la estructura de la zona sub-óxica. Las poblaciones microbianas, las cuales incluyen microorganismos heterotróficos y quimioautotróficos, crecen activamente a un ritmo que no es posible que se sostenga mediante el transporte vertical de oxidantes y reductores. La presente investigación sugiere que el anillo microbiano depende de la utilización de especies del azufre con estados de oxidación intermedio (sulfito, tiosulfato y S elemental) acoplada posiblemente con el ciclo de los óxidos metálicos. La producción de estas especies se mantiene por procesos activos de intrusión y por el transporte desde el continente de hierro y óxidos metálicos durante los episodios lluviosos.

BACKGROUND: Asthma is common and is often poorly controlled in adolescent subjects.

Colorectal cancer is one of the most common types of cancer with over fifty percent of patients presenting at an advanced stage. Retinoic acid is a metabolite of vitamin A and is essential for normal cell growth and aberrant retinoic acid metabolism is implicated in tumourigenesis. This study has profiled the expression of retinoic acid metabolising enzymes using a well characterised colorectal cancer tissue microarray containing 650 primary colorectal cancers, 285 lymph node metastasis and 50 normal colonic mucosal samples. Immunohistochemistry was performed on the tissue microarray using monoclonal antibodies which we have developed to the retinoic acid metabolising enzymes CYP26A1, CYP26B1, CYP26C1 and lecithin retinol acyl transferase (LRAT) using a semi-quantitative scoring scheme to assess expression. Moderate or strong expression of CYP26A1was observed in 32.5% of cancers compared to 10% of normal colonic epithelium samples (p

OBJECTIVE: To compare the relapse rate after a single intramuscular injection of a long acting corticosteroid, betamethasone, with oral prednisone in patients discharged from the emergency department (ED) for acute exacerbations of asthma.

Variability in the severity of asthma during various phases of the menstrual cycle has been frequently suspected. However, the hormonal changes that might affect mediators of bronchospasm have yet to be elucidated. The case of a 41-year-old woman suffering from longstanding asthma with life-threatening exacerbations is reported. The patient was treated with buserelin, a gonadotropin releasing hormone (GnRH) analogue, which created a temporary chemical menopause and thus permitted diagnosis of a premenstrual exacerbation of asthma and offered insight into potential therapy. GnRH analogues may therefore be of value in assessing women with severe asthma suspected to vary with the menstrual cycle. The addition of estrogens and progestins at the same time as treatment with GnRH analogue may be of value in determining the role of these hormones in the pathogenesis of menstrually related exacerbations of asthma.

The case of a 28-year-old man who experienced repeated episodes of pleuritic chest pain is reported. Eventual discovery of amylase in the pleural fluid and a supradiaphragmatic mass on computed tomography led to exploratory thoracotomy. A benign cystic teratoma was discovered in the pleural space overlying the left hemidiaphragm and connected by a peduncle to the thymus.

Background. Loss of visual function differs between immune-mediated optic neuropathies and is related to axonal loss in the optic nerve. This study investigated the diagnostic and prognostic value of a biomarker for neurodegeneration, the neurofilament heavy chain (NfH) in three immune-mediated optic neuropathies. Methods. A prospective, longitudinal study including patients with optic neuritis due to multiple sclerosis (MSON, n=20), chronic relapsing inflammatory optic neuritis (CRION, n=19), neuromyelitis optica (NMO, n=9), and healthy controls (n=28). Serum NfH-SMI35 levels were quantified by ELISA. Findings. Serum NfH-SMI35 levels were highest in patients with NMO (mean 0.79±1.51 ng/mL) compared to patients with CRION (0.13±0.16 ng/mL, P=0.007), MSON (0.09±0.09, P=0.008), and healthy controls (0.01±0.02 ng/mL, P=0.001). High serum NfH-SMI35 levels were related to poor visual outcome. Conclusions. Blood NfH-SMI35 levels are of moderate diagnostic and more important prognostic value in immune-mediated optic neuropathies. We speculate that longitudinal blood NfH levels may help to identify particular disabling events in relapsing conditions.

MotivationAdvances in mass spectrometry have led to the development of mass spectrometers with ion mobility spectrometry capabilities and dual-source instrumentation; however, the current software ecosystem lacks interoperability with downstream data analysis using open-source software and pipelines.ResultsHere, we present TIMSCONVERT, a data conversion high-throughput workflow from timsTOF Pro/fleX mass spectrometer raw data files to mzML and imzML formats that incorporates ion mobility data while maintaining compatibility with data analysis tools. We showcase several examples using data acquired across different experiments and acquisition modalities on the timsTOF fleX MS.Availability and implementationTIMSCONVERT and its documentation can be found at https://github.com/gtluu/timsconvert and is available as a standalone command-line interface tool for Windows and Linux, NextFlow workflow and online in the Global Natural Products Social (GNPS) platform.Supplementary informationSupplementary data are available at Bioinformatics online.

A critical need exists for early, accurate diagnosis of burn wound severity to help identify the course of treatment and outcome of the wound. Laser speckle imaging (LSI) is a promising blood perfusion imaging approach, but it does not account for changes in tissue optical properties that can occur with burn wounds, which are highly dynamic environments. Here, we studied optical property dynamics following burn injury and debridement and the associated impact on interpretation of LSI measurements of skin perfusion. We used spatial frequency domain imaging (SFDI) measurements of tissue optical properties to study the impact of burn-induced changes in these properties on LSI measurements. An established preclinical porcine model of burn injury was used (n = 8). SFDI and LSI data were collected from burn wounds of varying severity. SFDI measurements demonstrate that optical properties change in response to burn injury in a porcine model. We then apply theoretical modeling to demonstrate that the measured range of optical property changes can affect the interpretation of LSI measurements of blood flow, but this effect is minimal for most of the measured data. Collectively, our results indicate that, even with a dynamic burn wound environment, blood-flow measurements with LSI can serve as an appropriate strategy for accurate assessment of burn severity.

BackgroundGlial fibrillary acidic protein (GFAP) is a specific intermediate filament of the cytoskeleton of the astrocyte and may be used as a specific marker for astrocytic damage. It is detectable in the cerebrospinal fluid following a relapse caused by Multiple Sclerosis (MS) and Neuromyelitis Optica (NMO) spectrum disease. Higher levels are found following an NMO-related relapse. It is not known if GFAP is also detectable in the serum following such relapses. In particular, it is not known if lesions limited to the optic nerve release GFAP in sufficient quantities to be detectable within the serum. The aim of this study was to ascertain the extent to which serum GFAP levels can distinguish between an episode of optic neuritis (ON) related to NMO spectrum disease and ON from other causes.Methodology/principal findingsOut of 150 patients consecutively presenting to our eye hospital over the period March 2009 until July 2010, we were able to collect a serum sample from 12 patients who had presented with MS-related ON and from 10 patients who had presented with NMO spectrum disease-related ON. We also identified 8 patients with recurrent isolated ON and 8 patients with a corticosteroid-dependent optic neuropathy in the absence of any identified aetiology. GFAP was detectable in the serum of all but three patients (two patients with MS-related ON and one with recurrent optic neuritis). The median serum GFAP level in the patient group with NMO spectrum disease was 4.63 pg/mL whereas in all other cases combined together, this was 2.14 pg/mL. The difference was statistically significant (P = 0.01). A similar statistically significant difference was found when cases with pathology limited to the optic nerve were compared (P = 0.03).ConclusionsGlial pathology in NMO related optic neuritis is reflected in elevated serum GFAP levels independently of whether or not there is extra-optic nerve disease.

Alex McMahon and colleagues critique the International Conference on Harmonisation (ICH) guidance on good clinical practice (GCP), arguing that it is having a disastrous effect on noncommerical randomized clinical trials in Europe.