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The use of glucose sensors to triage post‐discharge follow‐up was investigated among hospital inpatients with type 2 diabetes. Feasibility, utility and patient satisfaction with this model of care were studied. Feasibility was 36.5%, with 90/198 (45.5%) inpatients discharged with glucose sensors but 9.0% unable to use glucose sensors effectively. Follow‐up plans were altered in 76.3% of the patients able to use the sensor technology. Patient satisfaction was high and was improved on follow‐up after 6 months. [ABSTRACT FROM AUTHOR]

This study examines the associations between force and velocity characteristics of forward skating and off‐ice speed, agility, and power of highly trained teenage ice hockey players. Players attending the Quebec ice hockey federation's off‐season evaluation camp were invited to participate in this study. Final sample consists of 107 highly trained teenage ice hockey players (Males: n = 38; 13.83 ± 0.38 years; Females: n = 69: 14.75 ± 0.90 years). Individual force–velocity profiles (F–V) were determined during a 44 m skating sprint. Off‐ice speed, agility, and power were measured using 30 m sprint, 5‐10‐5 agility, and standing long jump. Associations between F–V mechanical capabilities and off‐ice indicators were analyzed with correlational analyses and multivariate analysis of covariance (MANCOVA). Results of pooled data indicate that the three off‐ice measures had moderate associations with F0 and V0 and large associations with Pmax. Associations with Rfmax, Drf, and Sfv were moderate to small. F0 had stronger associations with off‐ice performance in female players while V0 was more important with male players. MANCOVA identified 5‐10‐5 times as the better predictor for F0 while 30 m sprints times better predicted V0. To maximize physical attributes of skating ability, practitioners are encouraged to focus on a general physical preparation for highly trained teenage players. Prioritizing types of exercises that use change of direction or acceleration and linear speed should have distinct effects on F0 and V0 on the ice. Highlights: A good general physical preparation is important for highly trained teenage ice hockey players as maximal running speed, change of direction ability, and leg power in the horizontal plane are largely associated with mechanical capabilities during maximal skating performance.Change of direction ability tends to be associated with the ability to generate force at low velocities on the ice (F0) while maximal running speed tends to be associated with the ability to generate force at high velocities on the ice (V0).Off‐ice abilities are more strongly associated to the ability to generate force at low velocities on the ice (F0) in highly trained female players than in highly trained male players. [ABSTRACT FROM AUTHOR]

This paper explores the effects of a public policy that reduces by 50% the use of mineral nitrogen in European agriculture. Our results show that, for the European Union, halving mineral fertilizer use leads to: a decrease in agricultural production, a substantial increase in nitrogen use efficiency, lower use of organic fertilizer and a loss of agricultural competitiveness. At the global level, it leads to greater nitrogen consumption if no measure is taken on the demand side. Ultimately, our research highlights the critical importance of supply side adjustments, particularly in terms of cropland area expansion. [ABSTRACT FROM AUTHOR]

In August 2021, the SOLEIL storage ring was restarted after the summer shutdown with a new bending magnet made entirely of permanent magnets. Producing a magnetic field of 2.8 T, it replaced one of the 32 electromagnetic dipoles (magnetic field of 1.7 T) of the ring to allow the ROCK beamline to exploit more intense photon fluxes in the hard X-ray range, thus improving the time resolution performances of the beamline for experiments carried out above 20 keV. The reduction of the new dipole magnetic gap required to produce the higher field has led to the construction and installation of a new vacuum vessel. The realization of the new dipole with permanent magnets was a technological feat due to the very strong magnetic forces. The permanent-magnet assembly required dedicated tools to be designed and constructed. Thanks to accurate magnetic measurements, a precise modelization of the new dipole was performed to identify its effects on the electron beam dynamics. The first measurements carried out on the ROCK beamline have highlighted the expected increase in photon flux, and the operation performances remain unchanged for the other beamlines. Here, the major developments and results of this innovative project are described in terms of technology, electron beam dynamics and photon beam performance on the ROCK beamline. [ABSTRACT FROM AUTHOR]

Background: Diabetes management often requires close cooperation between primary and specialist services, but a range of challenges in Australia and elsewhere make seamless care difficult. Aims: To evaluate the effectiveness of a new locality‐based integrated diabetes care service for people with Type 2 diabetes in an inner regional area. Methods: A quasi‐experimental evaluation comparing baseline and follow‐up clinical data collected from general practices and specialist services participating in an integrated diabetes care programme in an inner‐regional area. Patients had at least one specialist service consultation. The primary outcome was glycated haemoglobin (HbA1c). Results: Clinical data were collected for 178 (74.5%) of 239 patients (age ± standard deviation, 65 ± 11 years; 46% female; median (interquartile range) diabetes duration, 19 (11.0–24.0) years) from seven general practices over 33 months (median 18.5 months). There were reductions in HbA1c (0.7 ± 1.6% (8 ± 18 mmol/mol); P < 0.001), systolic blood pressure (5.8 ± 19.5 mmHg; P < 0.001), diastolic blood pressure (2.4 ± 14.3 mmHg; P = 0.04), total cholesterol (0.5 ± 1.3 mmoL/L; P < 0.001), low‐density lipoprotein (0.4 ± 0.9 mmoL/L; P < 0.001), body mass index (0.5 ± 1.6 kg/m2; P < 0.001) and weight (1.8 ± 4.7 kg; P < 0.001). The proportion without microalbuminuria increased from 48.4% to 59.3% (P = 0.03). Conclusions: Glycaemia and cardiovascular risk factors can be reduced in patients with long‐standing Type 2 diabetes by moving to a locality‐based integrated primary–secondary care diabetes care service. [ABSTRACT FROM AUTHOR]

Time‐of‐flight secondary ion mass spectrometry (TOF‐SIMS) imaging is a surface analysis technique that identifies and spatially resolves the chemical composition of a sample with a lateral resolution of less than 1 μm. Depth analyses can also be performed over thicknesses of several microns. In the case of a painting cross section, for example, TOF‐SIMS can identify the organic composition, by detecting molecular ions and fragments of binders, as well as the mineral composition of most of the pigments. Importantly, the technique is almost not destructive and is therefore increasingly used in cultural heritage research such as the analysis of painting samples, especially old paintings. In this review, state of the art of TOF‐SIMS analysis methods will be described with a particular focus on tuning the instruments for the analysis of painting cross sections and with several examples from the literature showing the added value of this technique when studying cultural heritage samples. [ABSTRACT FROM AUTHOR]

Background and Aims: Few meta‐analyses have been conducted to pool the most constant risk factors for problem gambling. The present meta‐analysis summarizes effect sizes of the most frequently assessed problem gambling risk factors, ranks them according to effect size strength and identifies any differences in effects across genders. Method: A random‐effects meta‐analysis was conducted on jurisdiction‐wide gambling prevalence surveys on the general adult population published until March 2019. One hundred and four studies were eligible for meta‐analysis. The number of participants varied depending on the risk factor analyzed, and ranged from 5327 to 273 946 (52% female). Weighted mean odds ratios were calculated for 57 risk factors (socio‐demographic, psychosocial, gambling activity and substance use correlates), allowing them to be ranked from largest to smallest with regard to their association with problem gambling. Results: The highest odds ratio (OR) was for internet gambling [OR = 7.59, 95% confidence interval (CI) = 5.24, 10.99, P < 0.000] and the lowest was for employment status (OR = 1.03, 95% CI = 0.87, 1.22, P = 0.718). The largest effect sizes were generally in the gambling activity category and the smallest were in the socio‐demographic category. No differences were found across genders for age‐associated risk. Conclusions: A meta‐analysis of 104 studies of gambling prevalence indicated that the most frequently assessed problem gambling risk factors with the highest effect sizes are associated with continuous‐play format gambling products. [ABSTRACT FROM AUTHOR]

Background: The goal of this study was to determine the relationship between postoperative weight change and breast cancer–related lymphedema (BCRL). Methods: In this cohort study, 1161 women underwent unilateral breast surgery for breast cancer from 2005 to 2020 and were prospectively screened for BCRL. Arm volume measurements were obtained via an optoelectronic perometer preoperatively, postoperatively, and in the follow‐up setting every 6 to 12 months. Mean follow‐up from preoperative baseline was 49.1 months. The main outcome was BCRL, defined as a relative volume change of the ipsilateral arm of ≥10% at least 3 months after surgery. Results: A total of 92 patients (7.9%) developed BCRL. Net weight loss versus net weight gain from baseline to last follow‐up was not protective against developing BCRL (hazard ratio, 1.38; 95% confidence interval, 0.89‐2.13; P =.152). Conclusions: Although weight loss may be recommended as part of an individualized lifestyle management program for overall health, weight loss alone may not decrease the risk of developing BCRL. Weight loss, when compared to weight gain, does not decrease the risk of breast cancer–related lymphedema (hazard ratio, 1.38; 95% confidence interval, 0.89‐2.13; P =.152). [ABSTRACT FROM AUTHOR]

Given the prospects of low short‐term emissions reduction, carbon removals (CDRs) are expected to play an important role in achieving ambitious mitigation targets in future scenarios of integrated assessment models (IAMs), particularly Bioenergy with Carbon Capture and Storage (BECCS). In this paper, we explore the IAMC 1.5℃ database to depict the characteristics of the two main CDR options present in mitigation scenarios: BECCS and afforestation/reforestation. We apply a linear mixed‐effect model to capture the specific regional and cross‐IAM effects. Results reveal that the distribution of BECCS and afforestation deployment differs across IAMs and regions and, to a second extent, time. BECCS is preferred in the scenarios not for its ability to expand energy use but actually because it appears as an alternative to afforestation, which is associated with a decrease in energy use. However, the regional distribution of CDR deployment does not show a common pattern across scenarios and IAMs. Therefore, a more comprehensive investigation is needed before it can support policy proposals. [ABSTRACT FROM AUTHOR]

Objective: With scale-up of antiretroviral therapy (ART) children, treatment failure and switch to subsequent ART regimens are common. Our objectives were to evaluate switching practices and identify factors associated among children and adolescents failing their first-line ART.Methods: A facility-based survey study was conducted in a cohort of children living with HIV experiencing virological failure (VF) at the Essos Hospital Centre of Yaounde, Cameroon. Data were collected using a standard questionnaire, and key variables were as follows: (a) VF defined as viral load (VL) > 1000 copies/ml, (b) rate of switch to second-line and (c) reason(s) for switching ART. Odds ratio (OR) with 95% confidence interval (CI) was used to assess the association between study variables, and P < 0.05 was considered statistically significant.Results: A total of 106 children experiencing VF were enrolled: median age was 8 [interquartile range (IQR): 3-15] years; 60.38% were boys and 39.62% were orphans of one/both parents. A proportion of 69% were at the WHO clinical stage III/IV, and 13.21% were experiencing immunological failure (CD4 < 200 cells/mm3 ). The median duration on first-line ART was 36 [IQR: 7-157] months prior to detecting VF, and the rate of switch to second-line ART was 70.75% (75/106). Delay in switching ART after a confirmed VF was 11 [IQR: 7-16] months. After switch to second-line ART, the median time to achieve undetectable VL (<40 copies/ml) was 14 [IQR: 9-21] months. Multivariate analysis revealed that only children with viral rebound (aOR = 0.09; 95% CI = 0.03-0.24) were less likely to be switched. Of note, being orphaned (aOR = 0.35, CI = 0.11-1.11), biological sex (aOR = 1.77, CI = 0.60-5.29) and immune status (aOR = 0.19, CI = 0.03-1.31, 0.09) had no significant effect on switching to second-line ART.Conclusion: In this paediatric population experiencing VF after about 3-4 years from ART initiation, the majority are switched to second-line ART after a delay of almost one year. Delayed switch to second-line was driven essentially by viral rebound, underscoring the need for close viral monitoring. [ABSTRACT FROM AUTHOR]

Nighttime compression is often overlooked for patients with breast cancer–related lymphedema, yet it is feasible, adherence to it is high, and arm volume and lymphedema‐specific quality of life improve with its use. Nighttime compression should be added to the self‐maintenance program for patients with breast cancer–related lymphedema. [ABSTRACT FROM AUTHOR]

Objective: Morbid obesity is associated with a higher independent risk of chronic kidney disease (CKD). Estimated glomerular filtration rate (eGFR) has been evaluated in a limited number of study participants with severe obesity.Methods: A total of 706 measured GFR (mGFR) results from 598 participants with obesity (BMI ≥ 35 kg/m2 ) were retrospectively collected. The performance of the Modification of Diet in Renal Disease (MDRD) equation, Chronic Kidney Disease-Epidemiology (CKD-EPI) equation, and deindexed eGFR were compared with mGFR from the gold standard technique (inuline or iohexol), adjusted (mGFRr) or nonadjusted (mGFR) to body surface area. Absolute bias, precision, and accuracy were calculated.Results: Mean mGFRr (58 ± 31 mL/min/1.73 m2 ) was significantly different from CKD-EPI and MDRD (P < 0.001). Mean mGFR (nonindexed) (70 ± 40 mL/min) was significantly higher than mGFRr (P < 0.001). eGFR showed important biases and low accuracies for CKD-EPI and MDRD (10.7 ± 10.7 and 12.2 ± 13.7 mL/min/1.73 m2 ; 78% vs. 75% respectively). Deindexation worsened bias and accuracy 30% (percentage of GFR estimates within 30% of mGFRr or mGFR) between eGFR and mGFR.Conclusions: eGFR overestimates mGFR and is associated with important biases and inaccuracies in patients with severe obesity, and deindexing eGFR worsens the overestimation. These findings may have important implications in examining kidney function in patients with obesity. [ABSTRACT FROM AUTHOR]

Introduction: Restless legs syndrome (RLS) is a highly prevalent sleep movement disorder usually accompanied by periodic limb movements of sleep (PLMS). The incidence of RLS and PLMS in patients with end‐stage renal disease (ESRD) on dialysis is much higher. Clinically, RLS and PLMS can co‐occur. We hypothesized that patients with ESRD on dialysis would have a distinct presentation of RLS, with a higher prevalence of PLMS. Methods: We examined clinical, demographic, biochemical, and polysomnographic characteristics of RLS in patients on dialysis matched to control subjects with normal renal function based on age, sex, body mass index, and frequency of apneas and hypopneas per hour of sleep, defined by the apnea and hypopnea index (AHI), in a proportion of 3:1. Patients with ESRD were on hemodialysis three times per week. Polysomnography was performed overnight in the sleep laboratory. Findings: Patients on dialysis compared to control subjects had a lower amount of N3 sleep (77.6 ± 39.9 minutes vs. 94.8 ± 33.7 minutes, p = 0.037) and REM sleep (55.6 ± 27.5 minutes vs. 74.1 ± 28.4 minutes, p = 0.006), regardless of the presence of RLS. Among the patients on dialysis, those with RLS had higher PLMS. In the control group, patients with RLS had a lower ferritin level, which was not observed in the dialysis group. There was a significant interaction between PLMS and ESRD (p = 0.001), with a higher prevalence of PLMS in patients with ESRD on dialysis in a model adjusted for AHI, sex, arousals, and age. Factors that were associated with PLMS were RLS (p = 0.003), ESRD (p = 0.0001), and AHI (p = 0.041), with an adjusted R2 of 0.321. Conclusion: RLS in patients with ESRD on dialysis is independently associated with PLMS, regardless of the severity of sleep apnea, arousals, and age. [ABSTRACT FROM AUTHOR]

Split‐hand/foot malformation (SHFM) is a genetically heterogeneous congenital limb malformation typically limited to a defect of the central rays of the autopod, presenting as a median cleft of hands and feet. It can be associated with long bone deficiency or included in more complex syndromes. Among the numerous genetic causes, WNT10B homozygous variants have been recently identified in consanguineous families, but remain still rarely described (SHFM6; MIM225300). We report on three novel SHFM families harboring WNT10B variants and review the literature, allowing us to highlight some clinical findings. The feet are more severely affected than the hands and there is a frequent asymmetry without obvious side‐bias. Syndactyly of third–fourth fingers was a frequent finding (62%). Polydactyly, which was classically described in SHFM6, was only present in 27% of patients. No genotype–phenotype correlation is delineated but heterozygous individuals might have mild features of SHFM, suggesting a dose‐effect of the WNT10B loss‐of‐function. [ABSTRACT FROM AUTHOR]

Verrucous hemangioma or verrucous venous malformation is a superficial venous malformation frequently misdiagnosed as a lymphatic malformation because of its classical hyperkeratotic appearance. Clinical characteristics of VVM were studied in patients with a histologically confirmed VVM, and validated in a prospective study of 18 patients. VVM was made of separated vascular elements with irregular shape, in a linear disposition, with variable thickness and keratosis. Its specific vascular pattern consisting of an erythematous patch with scattered small red to violet dots was easily identified using dermoscopy. In many cases, the typical clinical presentation of verrucous hemangioma is sufficient to establish the diagnosis and a biopsy may not be required. [ABSTRACT FROM AUTHOR]

Background: The potential usefulness of plasma phosphorylated tau (pTau) measurements for identifying individuals likely to be on the Alzheimer's disease (AD) continuum is evident from recent literature. Here we report the validation of an immunoassay for measurement of pTau181 in human plasma that will aid in the evaluation of Alzheimer's pathology in cases presenting with mild cognitive impairment. Method: The Simoa pTau‐181 assay is a fully automated 2‐step digital sandwich immunoassay that utilizes paramagnetic beads with capture antibodies and biotinylated detector antibodies. Digital detection is achieved using Simoa discs via SβG (Streptavidin‐ß‐galactosidase) and RGP (Resorufin‐β‐D‐galactopyranoside) amplification of specific pTau181 immune complexes. Harmonization to the Simoa pTau‐181 method described by Karikari et al (Mol Psychiatry. 2021;26(2):429‐442) using 80 samples, establishes commutability with published results from ADNI cohorts. Analytical validation on HD‐X instrument followed CLSI guidelines. Thirty‐four AD cases from the Amsterdam Dementia Cohort (age 66 ± 8 years) diagnosed according to the NIA‐AA diagnostic AD criteria and had a CSF biomarker‐confirmed AD diagnosis, 36 age‐ and sex‐matched (age 66 ± 8 years) cognitively healthy controls from the Dutch Brain Research Registry were included for clinical validation of this LDT. Result: The limits of detection (LoD) and quantification (LoQ) were 0.056 pg/mL and 0.276, respectively. Repeatability and reproducibility across 3 reagent lots using samples across the measuring range were 4.25% (95%CI:2.84‐5.65), 9.42% (95% CI: 4.46‐14.37) respectively. Linearity was demonstrated per CLSI EP06‐A, as ≤15% deviation at all dilutions. Cross reactivity against full length unphosphorylated‐Tau441 and synthetic peptides for pTau231 and pTau217 epitopes was below LoQ. ROC analysis resulted in a high AUC (area under the curve) of 0.897 (95% CI 0.825 to 0.969). Applying the cut‐offs described in Karikari1 (17.7 pg/mL) for this cohort resulted in a sensitivity of 94%, specificity of 72%. Conclusion: This test demonstrated acceptable analytical performance for CLIA laboratory implementation. High AUC of 0.897 to discriminate AD from non‐AD cases helps both rule‐in or rule‐out scenarios, and further allows for setting of cut‐off values that not only take the pretest probability, impact on screening algorithm, treatment protocols into consideration but also the costs incurred by misdiagnosis. [ABSTRACT FROM AUTHOR]

Rationale: Mass spectrometry imaging (MSI) is a powerful tool for mapping the surface of a sample. Time-of-flight secondary ion mass spectrometry (TOF-SIMS) and atmospheric pressure matrix-assisted laser desorption/ionization (AP-MALDI) offer complementary capabilities. Here, we present a workflow to apply both techniques to a single tissue section and combine the resulting data for the example of human colon cancer tissue. Methods: Following cryo-sectioning, images were acquired using the high spatial resolution (1 μm pixel size) provided by TOF-SIMS. The same section was then coated with a para-nitroaniline matrix and images were acquired using AP-MALDI coupled to an Orbitrap mass spectrometer, offering high mass resolution, high mass accuracy and tandem mass spectrometry (MS/MS) capabilities. Datasets provided by both mass spectrometers were converted into the open and vendor-independent imzML file format and processed with the open-source software MSiReader. Results: The TOF-SIMS and AP-MALDI mass spectra show strong signals of fatty acids, cholesterol, phosphatidylcholine and sphingomyelin. We showed a high correlation between the fatty acid ions detected with TOF-SIMS in negative ion mode and the phosphatidylcholine ions detected with AP-MALDI in positive ion mode using a similar setting for visualization. Histological staining on the same section allowed the identification of the anatomical structures and their correlation with the ion images. Conclusions: This multimodal approach using two MSI platforms shows an excellent complementarity for the localization and identification of lipids. The spatial resolution of both systems is at or close to cellular dimensions, and thus spatial correlation can only be obtained if the same tissue section is analyzed sequentially. Data processing based on imzML allows a real correlation of the imaging datasets provided by these two technologies and opens the way for a more complete molecular view of the anatomical structures of biological tissues. [ABSTRACT FROM AUTHOR]

Introduction Acetogenins are plant polyketides known to be cytotoxic and proposed as antitumor candidates. They are also suspected to be alimentary neurotoxins. Their occurrence as complex mixtures renders their dereplication and structural identification difficult using liquid chromatography coupled to tandem mass spectrometry and efforts are required to improve the methodology. Objective To develop a supercritical fluid chromatography (SFC) high-resolution tandem mass spectrometry method, involving lithium post-column cationisation, for the structural characterisation of Annonaceous acetogenins in crude extracts. Methodology The seeds of Annona muricata L. were extracted with methanol. Supercritical fluid chromatography of the extract, using a 2-ethylpyridine stationary phase column, was monitored using a high-resolution quadrupole time-of-flight mass spectrometer. Lithium iodide was added post-column in the make-up solvent. For comparison, the same extract was analysed using high-pressure liquid chromatography coupled to the same mass spectrometer, with a column based on solid core particles. Results Sensitivity was similar for both HPLC and SFC approaches. Retention behaviour and fragmentation pathways of three different isomer groups are described. A previously unknown group of acetogenins was also evidenced for the first time. Conclusion The use of SFC-MS/MS allows the reduction of the time of analysis, of environmental impact and an increase in the chromatographic resolution, compared to liquid chromatography. This new methodology enlightened a new group of acetogenins, isomers of montanacin-D. Copyright © 2017 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Aim Our understanding of how climate and fire have impacted quaking aspen ( Populus tremuloides Michx.) communities prior to the 20th century is fairly limited. This study analysed the period between 4500 and 2000 cal. yr bp to assess the pre-historic role of climate and fire on an aspen community during an aspen -dominated period. Location Long Lake, south-eastern Wyoming, central Rocky Mountains, USA. Methods Sedimentary pollen and charcoal were analysed to reconstruct the vegetation and fire history for a subalpine catchment currently dominated by lodgepole pine. Modern pollen-climate relationships were applied to the fossil pollen spectra to interpret past climate variability. Nonparametric ANOVA and Tukey HSD tests were used to determine whether the reconstructed climate and fire parameters were different throughout the study period. Results The modern pollen-climate data suggest a c. 150-year long drought centred on 4200 cal. yr bp, which caused the aspen ecotone to shift upslope. Between 3950 and 3450 cal. yr bp, an anomalous period of abundant quaking aspen pollen (Populus) occurred at the study site. Optimal climatic conditions coupled with frequent fires facilitated local quaking aspen dominance for roughly 500 years. After 3450 cal. yr bp, Populus pollen declined coincident with a return to less frequent fires and conifer dominance. Reconstructed climate variables from 550 cal. yr bp to present suggest conditions were not favourable for quaking aspen establishment at Long Lake. The Tukey HSD test confirms that the period of abundant Populus pollen was significantly different than any other period during this study. Main conclusions Quaking aspen shifted upslope in response to warmer temperatures, and persisted for roughly 500 years as a result of optimal climatic conditions and frequent fire events. [ABSTRACT FROM AUTHOR]

Objectives To evaluate the histopathological results after radical prostatectomy ( RP) in patients that had normal preoperative multiparametric magnetic resonance imaging (mp MRI), in order to determine whether they had significant or insignificant disease. Moreover, we evaluated the influence of the expertise of the radiologist on the results. Patients and Methods We retrospectively included patients who underwent RP in our centre and who had a preoperative negative mp MRI. The MRIs were considered negative when no suspicious lesion was seen or when the Prostate Imaging Reporting and Data System version 1 score was <7. We used Pathological tumour-node-metastasis staging and Gleason score on pathology reports, and whole-mount sections to calculate tumour volume. Results We identified 101 patients from 2009 to 2015. Final pathology showed that 16.9% had extraprostatic extension, 13.8% had primary Gleason pattern 4 (4 + 3 and above), 47.5% had secondary Gleason pattern 4 or 5, and 55.9% and 20.6% had a main tumour volume of ≥0.5 and ≥2 mL, respectively. When limiting the analysis to expert reading only, the numbers improved: only one patient (3.4%) had extraprostatic extension ( P < 0.05), one patient (3.4%) had primary Gleason pattern 4 ( P = 0.05), and 64.7% and 5.9% had a main tumour volume of ≥0.5 and ≥2 mL, respectively ( P = 0.01). Conclusion A negative MRI does not guarantee the absence of significant prostate cancer. [ABSTRACT FROM AUTHOR]

Aim: Atypical migraine with aura can be challenging to diagnose. Arterial-spin-labelling (ASL) is able to non-invasively quantify brain perfusion. Our aim was to report cerebral blood flow (CBF) alterations using ASL, at the acute phase of atypical migraine with aura in children.Method: Paediatric patients were retrospectively included if (1) referred for acute neurological deficit(s), (2) underwent brain magnetic resonance imaging (MRI) at presentation with ASL sequence, and (3) had subsequent diagnosis of migraine with aura. Neurological symptom-free controls were matched for age. Twenty-eight regions of interest (ROIs) were drawn on CBF maps for each participant/control.Results: Ten patients were included (median age 13y, range 8-16y). Eight of 10 had multiple aura symptoms during the episode. For every patient, CBF was decreased in a brain region consistent with symptoms when MRI was performed less than 14 hours after onset (n=7 patients) and increased if the MRI was performed 17 hours or more after (n=4 MRIs).Interpretation: MRI-ASL appears to be a promising tool for the diagnostic workup and differentials exclusion in paediatric migraine with aura. Constant and time-consistent non-territorial CBF modifications were found in our sample providing additional insight to migraine with aura pathophysiology. The authors encourage implementing this sequence at the acute phase of unexplained paediatric neurological deficits, with or without accompanying headache. [ABSTRACT FROM AUTHOR]

The preparation of tropical wood surface sections for time-of-flight secondary ion mass spectrometry imaging is described, and the use of delayed extraction of secondary ions and its interest for the analysis of vegetal surface are shown. The method has been applied to the study by time-of-flight secondary ion mass spectrometry imaging with a resolution of less than one micron of a tropical wood species, Dicorynia guianensis, which is one of the most exploited wood in French Guiana for its durable heartwood. The heartwood of this species exhibits an economical importance, but its production is not controlled in forestry. Results show an increase of tryptamine from the transition zone and a concomitant decrease of inorganic ions and starch fragment ions. These experiments lead to a better understanding of the heartwood formation and the origin of the natural durability of D. guianensis. Copyright © 2016 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Southeast Asia is often considered a quintessential Sprachbund where languages from five different language phyla have been converging typologically for millennia. One of the common features shared by many languages of the area is tone: several major national languages of the region have large tone inventories and complex tone contours. In this paper, we suggest a more fine-grained view. We show that in addition to a large number of atonal languages, the tone languages of the region are actually far more diverse than usually assumed, and employ phonation type contrasts at least as often as pitch. Along the same lines, we argue that concepts such as tone and register, while descriptively useful, can obscure important underlying similarities and impede our understanding of the behavior of phonetic properties, typological regularities, and diachrony. We finally draw the reader's attention to some issues of current interest in the study of tone and phonation in Southeast Asia and describe some technical developments that are likely to allow researchers to address new lines of research in years to come. [ABSTRACT FROM AUTHOR]

Because of tensions on fossil energy and phosphorus markets, the rise in fertilizer prices observed during the last decades may continue in the future, putting into question production pathways relying heavily on crop intensification. To evaluate how, in this context, economic choices may alter crop yields, we first construct different fertilizer price scenarios to 2050 based on an econometric relation with oil and gas prices. Other possible scenarios, such as the continuation of historical trends, are also considered. The resulting changes in fertilizer price range between +0.8% and +3.6% per year over the 2005-2050 period. These scenarios are tested in a global land-use model incorporating an endogenous representation of the land-fertilizer substitution. We find that the supply-side response to rising fertilizer prices could lower crop yields in 2050 from −6% to −13%, with a corresponding increase in global cropland area ranging between 100 and 240 Mha if the demand for food and nonfood products has to be met. The sensitivity of these results is tested with regard to assumptions on food consumption, change in potential yield and nutrient use efficiency. [ABSTRACT FROM AUTHOR]

RATIONALE: In Time-of-Flight Secondary Ion Mass Spectrometry (TOF-SIMS), pulsed and focused primary ion beams enable mass spectrometry imaging, a method which is particularly useful to map various small molecules such as lipids at the surface of biological samples. When using TOF-SIMS instruments, the focusing modes of the primary ion beam delivered by liquid metal ion guns can provide either a mass resolution of several thousand or a sub-μm lateral resolution, but the combination of both is generally not possible. METHODS:With a TOF-SIMS setup, a delayed extraction applied to secondary ions has been studied extensively on rat cerebellum sections in order to compensate for the effect of long primary ion bunches. RESULTS: The use of a delayed extraction has been proven to be an efficient solution leading to unique features, i.e. a mass resolution up to 10000 at m/z 385.4 combined with a lateral resolution of about 400 nm. Simulations of ion trajectories confirm the experimental determination of optimal delayed extraction and allow understanding of the behavior of ions as a function of their mass-to-charge ratio. CONCLUSIONS: Although the use of a delayed extraction has been well known for many years and is very popular in MALDI, it is much less used in TOF-SIMS. Its full characterization now enables secondary ion images to be recorded in a single run with a submicron spatial resolution and with a mass resolution of several thousand. This improvement is very useful when analyzing lipids on tissue sections, or rare, precious, or very small size samples. [ABSTRACT FROM AUTHOR]

Aim To address risk of first or recurrent cerebral haemorrhage in children with sickle-cell disease ( SCD) who are being managed with modern stroke prevention strategies. Method A systematically followed SCD paediatric cohort was retrospectively studied over a 9-year period. Haemorrhagic risk was defined as intracranial haemorrhage occurrence or intracranial aneurysm diagnosis during the study period. Ischaemic risk was defined as cerebrovascular ischaemic event occurrence or transcranial Doppler/magnetic resonance imaging hallmarks of ischaemic risk finding during the study period. Results Among the 251 patients in the cohort, 36 patients were included in the ischaemic group. Seven patients were included in the haemorrhagic group, of which five also met the criteria for the ischaemic group. Age at first haemorrhagic symptom/hallmark of risk was older (10.4 vs 6.2 years old, p=0.036). Nine intracranial saccular aneurysms were found, mostly on the posterior circulation. Two patients had endovascular embolization. Interpretation The ratio of ischaemic to haemorrhagic risk was not modified with modern management compared with historical series. Intracranial aneurysm in children with SCD had specific characteristics, close to intracranial aneurysms described in adults with SCD. Data favoured concurrent development of intracranial SCD-associated anterior stenosis and posterior dilation, suggesting common pathophysiology and management strategies. [ABSTRACT FROM AUTHOR]

Recent developments in instrumentation, ion beams or analyzers, for cluster time-of-flight secondary ion mass spectrometry (TOF-SIMS) imaging are described here. The methods which are employed to increase the sensitivity or to perform three-dimensional analyses in the organic materials are also illustrated. This review shows the improvements made for lipid imaging by cluster TOF-SIMS in various types of material and applications, and gives reasons for the expansion of its utilization. © 2013 Wiley Periodicals, Inc. Mass Spec Rev 33: 442-451, 2014. [ABSTRACT FROM AUTHOR]

The development of 'omics' sciences offers new opportunities for the study of neurodegenerative diseases but increases at the same time the sample demand on brain banks that collect and store valuable human post-mortem tissue. Our study aims to evaluate in lipidomics the potential of formalin-fixed tissue compared with the cryopreservation method, considered as the gold standard for biochemical research. Two complementary liquid chromatography/mass spectrometry analytical platforms were used on the basis of hybrid quadrupole time-of-flight and triple quadrupole mass spectrometers. Untargeted fingerprinting, semitargeted profiling of specific lipid classes and targeted monitoring of lipid species were performed in formalin-fixed and cryopreserved samples to provide detailed information at the molecular level on the formalin-induced alterations of the brain tissue. In vitro incubations of lipid standards were also performed to further describe the degradation processes induced by formaldehyde. Phospholipid compounds were found to be extensively hydrolysed, whilst the sphingolipid ones were preserved. N-methylation and N-formylation of amine-containing phospholipids have also been evidenced. These findings show that the potential detrimental effect of formalin on the analytes of interest must be taken into account when analysing formalin-fixed samples. Copyright © 2014 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

ABSTRACT One of the most significant challenges in developing therapeutic monoclonal antibodies (mAbs) is their unpredictable solubilities and viscosities at the high concentrations required for subcutaneous delivery. This challenge has motivated the development of screening assays that rapidly identify mAb variants with minimal self-association propensities and/or formulation conditions that suppress mAb self-association. Here we report an improved version of self-interaction nanoparticle spectroscopy (SINS) capable of characterizing both repulsive and attractive self-interactions between diverse mAbs. The basis of SINS is that self-interactions between mAbs immobilized on gold nanoparticles increase (repulsion) or decrease (attraction) interparticle distances, which shift the wavelength of maximum absorbance (plasmon wavelength) in opposite directions. We find that the robustness of SINS is improved by varying the amount of immobilized mAb by co-adsorbing a polyclonal antibody. The slopes of the plasmon wavelength shifts as a function of the amount of immobilized mAb (0.01-0.1 mg/mL) are correlated with diffusion interaction parameters measured at two to three orders of magnitude higher antibody concentrations. The ability of SINS to rapidly screen mAb self-association in a microplate format using dilute mAb solutions makes it well suited for use in diverse settings ranging from antibody discovery to formulation. Biotechnol. Bioeng. 2014;111: 1513-1520. © 2014 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

A new approach to treating Duchenne muscular dystrophy was investigated by using the ester or amide covalent association of arginine [nitric oxide (NO) pathway] and butyrate [histone deacetylase (HDAC) inhibition] in max mice and patient myotubes. Two prodrugs were synthesized, and the beneficial effects on dystrophic phenotype were studied. Nerve excitability abnormalities detected in saline-treated mice were almost totally rescued in animals treated at low doses (50-100 mg/kg/d). Force and fatigue resistance were improved ≈60% and 3.5-fold, respectively, and the percentage of necrosis in heart sections was reduced ≈90% in the treated mice. A decrease of >50% in serum creatine kinase indicated an overall improvement in the muscles. Restoration of membrane integrity was studied directly by measuring the reduction (≈74%) of Evans blue incorporation in the limb muscles of the treated animals, the increase in utrophin level, and the normalization of lipid composition of the heart. In cultures of human myotubes (primary cells and cell line), both prodrugs and HDAC inhibitors increased by 2- to 4-fold the utrophin level, which was correctly localized at the membrane. β-Dystroglycan and embryonic myosin protein levels were also increased. Finally, a 50% reduction in the number of spontaneous Ca2+ spikes was observed after treatment with NO synthase substrate and HDAC inhibitors. Overall, the beneficial effects were obtained with doses 10 (in vivo) and 5 (in vitro) times lower than those of the salt formulation. Altogether, these data constitute proof of principle of the beneficial effects of low doses of arginine hutyrate derivatives on muscular dystrophy, enhancing the NO pathway and inhibiting HDAC. [ABSTRACT FROM AUTHOR]

Objective To assess potential causes of woody plant encroachment into desert grassland systems using a 5500-yr-old sediment record from a ciénega in New Mexico. Location Cloverdale Ciénega, southwestern New Mexico. Methods Utilizing fossil pollen and charcoal preserved in wetland sediments, a long-term record of variations in vegetation composition and fire activity was generated. The record was compared to published data on drought, the El Niño/Southern Oscillation ( ENSO), carbon dioxide concentrations and known dates of grazing impacts to evaluate various hypotheses regarding the timing and causes of woody plant encroachment in desert grasslands. Results The woody plant encroachment observed in the past 200 yrs is unprecedented in the context of the previous 5500 yrs of vegetation history. The observed increase in woody plant abundance was not related to droughts or changes in ENSO event frequency, and was contemporaneous with the rise in atmospheric CO2 and known grazing impacts. Charcoal influx increased in conjunction with historic woody plant pollen abundance and therefore the encroachment was not related to fire exclusion. Conclusions The long-term sediment record from Cloverdale Ciénega provides the context for evaluation of the various hypotheses for woody plant encroachment. At Cloverdale Ciénega we demonstrate that woody plant encroachment of the last 200 yrs is unprecedented and outside of the historic natural range of variability of the previous five millennia. We also demonstrate that woody plant encroachment is not related to climatological changes such as drought or increases in ENSO frequency. Increases in woody plant pollen are associated with increases in carbon dioxide, and high-intensity grazing during the late 19th and early 20th centuries. [ABSTRACT FROM AUTHOR]

Aim Hemiconvulsion-hemiplegia syndrome ( HHS) is a rare severe epilepsy of infancy consisting of unilateral convulsive status epilepticus immediately followed by transient or lasting ipsilateral hemiplegia. HHS may occur either in patients with previous brain pathology or without any identified cause, so-called 'idiopathic HHS'. Method We retrospectively analysed clinical and MRI longitudinal findings of a series of 10 patients (six females, four males) presenting with HHS. Age at the study inclusion ranged from 2 years 6 months to 15 years (mean of 5y 10mo, median 4y 2mo). After defining magnetic resonance imaging ( MRI) features as 'typical', i.e. strictly unilateral involvement, and 'atypical', i.e. bilateral, we compared clinical data from both groups. Cognitive level was assessed using Brunet-Lézine or Wechsler scales. Results HHS occurred at a mean age of 20.5 months (range 8-48mo). In all cases, status epilepticus lasted for more than 1 hour and was characterised by unilateral clonic seizures followed by ipsilateral hemiplegia (persistent in five patients). Two patients in this series died: the first from multi-organ failure 2 weeks after the status epilepticus and the other from a second episode of ipsilateral intractable febrile status epilepticus 3 years after the first episode. Early MRI (days 1-7 from status epilepticus) showed hemispheric cytotoxic oedema in all, extending to the contralateral side for one. T2 hyperintensity in the basal ganglia was disclosed in 70% of patients and in the hippocampus in 60%. After 1 month (in intermediate and chronic phases), all surviving patients but one showed hemispheric cortical atrophy corresponding to the regions involved during the early stage. Comparing clinical features of patients presenting with 'typical' features, to those with 'atypical' findings, the second group presented psychomotor delay before status epilepticus. Interpretation This series underlines the major value of early MRI for the prompt diagnosis of HHS, and shows that involvement of subcortical structures has been underestimated. Hippocampal involvement is not constant. [ABSTRACT FROM AUTHOR]

ABSTRACT Objective To determine whether a standard complete fetal anatomical survey, as recommended for ultrasound examination guidelines, is feasible using a standardized magnetic resonance imaging ( MRI) protocol. Methods Based on guidelines for ultrasound examination, we created a specific MRI protocol for fetal anatomical survey. This protocol was then tested prospectively in 100 women undergoing fetal MRI examination for various specific indications at a median gestational age of 30 weeks. The feasibility of using MRI to perform the fetal anatomical survey was analyzed by two reviewers (A and B) based on 26 predefined anatomical criteria, yielding a score ranging from 0 to 26 (26 meaning successful complete anatomical study). Reproducibility was analyzed using percentage agreement and modified kappa statistics. Results The mean score for the standardized MRI anatomical survey was 24.6 ( SD, 1.4; range, 15-26) for Reviewer A and 24.2 ( SD, 1.7; range, 15-26) for Reviewer B (P = 0.1). Twenty-two, two and two criteria could be assessed in > 95%, 80-95% and < 80% of cases by Reviewer A and 19, four and three criteria could be assessed in > 95%, 80-95% and < 80% of cases by Reviewer B. For both reviewers, the two most difficult criteria to evaluate were aorta and pulmonary artery. Inter-reviewer agreement was above 90% for 22 of the 26 anatomical criteria and adjusted kappa coefficients for each criterion demonstrated good, moderate and poor agreement for 22, two and two criteria, respectively. Conclusion Our data support the hypothesis that standardized fetal anatomical examination might be achieved and reproducible using MRI, although improvement is required for the cardiac part of the examination. Copyright © 2013 ISUOG. Published by John Wiley & Sons Ltd. [ABSTRACT FROM AUTHOR]

Decreasing spatial transaction and trade costs have given rise to growing economic specialization of cities. While most studies focus on industries as the primary manifestation of urban specialization, a growing body of literature examines occupational functions, i.e., activities and tasks performed within a given industry or firm. This paper explores how the two dimensions (industries and functions) interact across the urban system and their relative importance over time. Is there a trend toward increasing functional specialization in the Canadian urban system? How much of this phenomenon is attributable to spatial shifts in regional industrial structures as opposed to spatial divisions within industries? The paper uses a unique data set drawn from Statistics Canada Census microdata files between 1971 and 2006. Based on the employed population, the data are spatially organized and cross-tabulated over industries and occupational groups. A decomposition methodology is used to compare the relative weights of industry and regional (functional) effects in accounting for the changing spatial division of functions across Canadian urban areas. Clear patterns of increasing functional specialization are found within the Canadian urban system. Regional effects are generally greater than industry effects, suggesting that spatial divisions of functions (spatial shifts within industries) are progressing more rapidly than regional shifts in industrial structure. [ABSTRACT FROM AUTHOR]

Abstract: Previous research has documented associations of addiction with delinquency and psychological problems. However, few studies have evaluated their influence on adolescent's drug use trajectories. The current study aims to examine the influence of these factors on the recovery trajectories of 199 youths aged 15.6 years on average admitted to inpatient and outpatient addiction treatment centers, followed up three and six months later. Results indicate that youth who show higher severity of drug abuse exhibit greater improvement than youth with a lower severity of drug abuse at the onset of treatment. Although psychological problems were associated with baseline drug use, they did not influence drug use trajectory over time. Only delinquency influenced the recovery trajectories of these youth. Results suggest that a high level of delinquency can have a significant effect on the drug recovery process of adolescents and that interventions should attempt to reduce both drug use and delinquency. [Copyright &y& Elsevier]

ABSTRACT Objectives (1) To study the use and diagnostic value, as a complement to ultrasound, of helical computed tomography (helical CT) to differentiate normal fetuses from cases of skeletal dysplasia; (2) to define the most relevant indications for helical CT; and (3) to evaluate its diagnostic performance with respect to radiological criteria considered discriminatory. Methods This was a retrospective study from 2005 to 2008 in 67 pregnant women who underwent helical CT after 26 weeks of gestation for suspected fetal skeletal dysplasia due to fetal shortened long bones on ultrasound (≤ 10thpercentile), either alone or associated with other bone abnormalities. The results were compared with pediatric examinations in 41 cases and with fetal autopsy findings after elective termination of pregnancy in the others. Results Helical CT had a sensitivity of 82%, specificity of 91% and positive and negative predictive values of 90% and 83%, respectively, for diagnosis of fetal skeletal dysplasia. An etiological diagnosis that had not been suspected at ultrasound was specified in 15% of cases and diagnoses suspected at ultrasound were confirmed in 24% and discounted in 43% of cases. The prevalence of skeletal dysplasia was increased in cases of micromelia < 3rd percentile or if there was a combination of bone signs. Helical CT showed 69% sensitivity in identifying individual predefined pathological bone signs which were confirmed on fetal autopsy findings. Conclusion Helical CT is a key examination, in combination with ultrasound, in the diagnosis of fetal skeletal dysplasia from 26 weeks of gestation. It should be reserved for cases with severe micromelia below the 3rd percentile and for those with micromelia ≤ 10th percentile associated with another bone sign. A checklist of discriminatory signs is proposed. Copyright © 2012 ISUOG. Published by John Wiley & Sons Ltd. [ABSTRACT FROM AUTHOR]

While ToF-SIMS is typically used to localize elemental ions in inorganic materials, it is also successfully utilized since several years to get images of a large variety of organic compounds, such as lipids (up to m/z 1500) at the surface of biological tissue sections. This technique can be associated with histology for medical diagnosis in order to correlate structural features with ion images. The possibility to use the same tissue section for both histology and mass spectrometry imaging would be a major advantage in terms of sample preparation and precision on the histological structure localization. In this study, on the one hand, rat brain sections were stained with Hematoxylin-Eosin (HE) after a ToF-SIMS surface analysis, and on the other hand, the lipid mapping with ToF-SIMS was performed after the HE staining procedure. In the first case, we evidenced that the high vacuum conditions applied in ToF-SIMS imaging did not disturb the staining neither the recognition of the brain structures. In the second case, a cholesterol fragment ion, chosen for imaging, was still detected in the brain structure after HE staining. However, it has not been possible to totally overlay the optical image before the staining with the ionic images after the staining, likely because of a distention of the tissue. Copyright © 2012 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]