Determining the likelihood and cost of detecting reductions of nitrate­nitrogen concentrations in groundwater across New Zealand.

Nitrate­nitrogen (NO3-N) is a contaminant of concern in groundwater worldwide. Stakeholders need information on the ability to detect changes in NO3-N concentrations to prove that land management practices are meeting water quality aims. We created a database of quarterly to monthly NO3-N measurements in 948 sites across New Zealand; 186 of those sites had mean residence time (MRT) data. New Zealand has set a target of sufficient land use mitigations in the next 30 years to ensure steady state surface water concentrations do not exceed 2.4 mg L-1. Here we assess whether the current monitoring network could identify the impacts of these mitigations, assuming that the mitigations are successfully implemented at the source. Only 41 % of the network could detect statistically significant reductions with the current standard quarterly sampling after 30 years of monitoring. The percentage of sites increased to 60 % with increased monitoring frequency (often weekly) but this required a 100-300 % increase in monitoring costs. However, policy makers and stakeholders typically require information on policy and mitigation effectiveness within 5-10 years. Detection within 5-10 years was very unlikely (0-20 % of sites) regardless of the sampling frequency. Importantly, these analyses include the impacts of groundwater lag and temporal dispersion on the likelihood of detecting change, ignoring these impacts, incorrectly, yields a much higher likelihood of detecting reductions. We conclude that the current monitoring network is unlikely to be fit for the purpose of detecting NO3-N reductions within practical timeframes or budgets. Furthermore, we conclude that lag and temporal dispersion effects must be included in detection power calculations; we therefore recommend that MRT data is regularly collected. We also provide a python package to enable easy detection power calculations with lag and temporal dispersion impacts, thereby supporting the development of robust change-detection monitoring networks.

Hindlimb and pelvic anatomy of Caiman yacare (Archosauria, Pseudosuchia): Myology and osteological correlates with emphasis on lower leg and autopodial musculature.

The anatomy of the archosaurian pelvis and hindlimb has adopted a diversity of successful configurations allowing a wide range of postures during the evolution of the group (e.g., erect, sprawling). For this reason, thorough studies of the structure and function of the pelvic and hindlimb musculature of crocodylians are required and provide the possibility to expand their implications for the evolution of archosaurian locomotion, as well as to identify potential new characters based on muscles and their bony correlates. In this study, we give a detailed description of the pelvic and hindlimb musculature of the South American alligator Caiman yacare, providing comprehensive novel information regarding lower limb and autopodial muscles. Particularly for the pedal muscles, we propose a new classification for the dorsal and ventral muscles of the autopodium based on the organisation of these muscles in successive layers. We have studied the myology in a global background in which we have compared the Caiman yacare musculature with other crocodylians. In this sense, differences in the arrangement of m. flexor tibialis internus 1, m. flexor tibialis externus, m. iliofibularis, mm. puboischiofemorales internii 1 and 2, between Ca. yacare and other crocodylians were found. We also discuss the muscle attachments that have different bony correlates among the crocodylian species and their morphological variation. Most of the correlates did not exhibit great variation among the species compared. The majority of the recognised correlates were identified in the pelvic girdle; additionally, some bony correlates associated with the pedal muscles are highlighted here for the first time. This research provides a wide framework for future studies on comparative anatomy and functional morphology, which could contribute to improving the character definition used in phylogenetic analyses and to understand the patterns of musculoskeletal hindlimb evolution.

"African" acral keratoderma: Further evidence for a single entity. A retrospective study of 42 patients.

BACKGROUND: Several phenotypes of non-inflammatory palmar and plantar keratoderma (PPK) have been described in patients of Sub-Saharan African descent. They include keratosis punctata of the palmar creases, marginal keratoderma, also known as acrokeratoelastoidosis or focal acral hyperkeratosis, knuckle pads, other forms of diffuse hyperkeratosis, the very rare "mosaic acral keratosis", and ainhum. A previous survey has shown that these various forms of PPK are particularly frequent in patients of Sub-Saharan African descent and that they commonly occur concurrently, suggesting that they could form part of a single entity called "African" Acral Keratoderma (AAK). AIM: To assess the validity of the concept of AAK and clarify its main characteristics. METHODS: A retrospective, descriptive, monocenter study was carried out on patients with AAK seen at our institution between 2009 and 2020. RESULTS: There were 42 patients (median age 38 years, range: 12-69 years), all of Sub-Saharan African descent. The male-female sex ratio was 0.3. Thirty-three (78%) had diffuse keratoderma, 25 (59%) had marginal keratoderma on their hands and/or feet, 20 (48%) had knuckle pads, 20 (48%) had keratosis punctata of the palmar creases, 3 had ainhum, and 2 had mosaic acral keratoderma. Mixed forms were seen in 76% of the patients (n = 32). Familial histories were reported by 17 patients (40%). Treatment was topical in over 90% of patients and systemic in 9 patients (21%). Ainhum was managed surgically. CONCLUSION: This retrospective study provides additional evidence for the concept of AAK. A genetic origin is suggested by the familial aggregation of cases.

The nature of deep overturning and reconfigurations of the silicon cycle across the last deglaciation.

Changes in ocean circulation and the biological carbon pump have been implicated as the drivers behind the rise in atmospheric CO2 across the last deglaciation; however, the processes involved remain uncertain. Previous records have hinted at a partitioning of deep ocean ventilation across the two major intervals of atmospheric CO2 rise, but the consequences of differential ventilation on the Si cycle has not been explored. Here we present three new records of silicon isotopes in diatoms and sponges from the Southern Ocean that together show increased Si supply from deep mixing during the deglaciation with a maximum during the Younger Dryas (YD). We suggest Antarctic sea ice and Atlantic overturning conditions favoured abyssal ocean ventilation at the YD and marked an interval of Si cycle reorganisation. By regulating the strength of the biological pump, the glacial-interglacial shift in the Si cycle may present an important control on Pleistocene CO2 concentrations.

Nabothian cyst content: A potential pitfall for the diagnosis of invasive cancer on Pap test cytology.

Nabothian cysts are common, benign findings of the squamocolumnar junction of the adult cervix. These cysts are filled with mucus and can also contain proteinaceous material, neutrophils, or neutrophil debris. Nabothian cysts can be broken by the spatula during smear taking, may stick to the brush and be smeared onto slides in conventional cytology or dissolved in the preserving solution for liquid-based cytology (LBC) preparations. The granular content of Nabothian cysts may be mistaken for the tumor diathesis (TD) pattern associated with invasive carcinoma. In the case described, the patient presented a high-grade squamous intraepithelial lesion associated with granular material (Nabothian cyst content) that we considered erroneously on LBC to be TD-like material, thus, raising the suspicion of invasive carcinoma. To the best of our knowledge, this is the first report showing that Nabothian cyst content may present a potential pitfall in the diagnosis of invasive carcinoma on LBC.

DNA Sequences in Centromere Formation and Function.

Faithful chromosome segregation during cell division depends on the centromere, a complex DNA/protein structure that links chromosomes to spindle microtubules. This chromosomal domain has to be marked throughout cell division and its chromosomal localization preserved across cell generations. From fission yeast to human, centromeres are established on a series of repetitive DNA sequences and on specialized centromeric chromatin. This chromatin is enriched with the histone H3 variant, named CENP-A, that was demonstrated to be the epigenetic mark that maintains centromere identity and function indefinitely. Although centromere identity is thought to be exclusively epigenetic, the presence of specific DNA sequences in the majority of eukaryotes and of the centromeric protein CENP-B that binds to these sequences, suggests the existence of a genetic component as well. In this review, we will highlight the importance of centromeric sequences for centromere formation and function, and discuss the centromere DNA sequence/CENP-B paradox.

Bilateral hand transplantation: Supporting the patient's choice.

Bilateral hand transplantation, as a fairly new reconstructive option for amputees, raises major ethical questions. This article, which is based on the reflections arising from the rich experience of Lyon's team in this field, addresses the topic of supporting the patient in his choice for or against this procedure. How should autonomy be understood in this particular setting? The developing field of composite tissue allotransplantation needs to establish a common thinking on this subject. The article emphasises that, even if it is their right to decide, patients have to be carefully supported to help them make the most consolidated choice possible in this challenging procedure. We deal with the question of the choice between the uncertainty in this innovative procedure and a life-threatening treatment to alleviate a handicap. We outline that the entire process of hand allograft is a unique opportunity for the patients to strengthen and exercise their autonomy in interaction with the medical team.

How obesity relates to socio-economic status: identification of eating behavior mediators.

BACKGROUND: Socio-economic status (SES) is a strong determinant of eating behavior and the obesity risk. OBJECTIVE: To determine which eating and lifestyle behaviors mediate the association between SES and obesity. METHODS: We performed a case-control study of 318 obese people and 371 non-obese people in northern France. Ten eating behavior traits were assessed using the Three-Factor Eating Questionnaire Revised 21-Item and an eating attitude questionnaire (on plate size, the number of servings, reasons for stopping eating and the frequency of eating standing up, eating in front of the television set (TV) and eating at night). The SES score (in three categories) was based on occupation, education and income categories. Mediation analysis was performed using the test of joint significance and the difference of coefficients test. RESULTS: The age- and gender-adjusted obesity risk was higher for individuals in the low-SES groups (odds ratio (OR) (95% confidence interval (CI)=1.82 (1.48-2.24), P<0.0001). Additional servings were associated with a higher obesity risk (OR=3.43, P<0.0001). Cognitive restraint (P<0.0001) and emotional eating (P<0.0001) scores were higher in obese participants than in non-obese participants but did not depend on SES. Of the 10 potential factors tested, eating off a large plate (P=0.01), eating at night (P=0.04) and uncontrolled eating (P=0.03) significantly mediated the relationship between SES and obesity. CONCLUSION: Our results highlighted a number of obesogenic behaviors among socially disadvantaged participants: large plate size, uncontrolled eating and eating at night were significant mediators of the relationship between SES and the obesity risk.

Light-sensitive brain pathways and aging.

Notwithstanding its effects on the classical visual system allowing image formation, light acts upon several non-image-forming (NIF) functions including body temperature, hormonal secretions, sleep-wake cycle, alertness, and cognitive performance. Studies have shown that NIF functions are maximally sensitive to blue wavelengths (460-480 nm), in comparison to longer light wavelengths. Higher blue light sensitivity has been reported for melatonin suppression, pupillary constriction, vigilance, and performance improvement but also for modulation of cognitive brain functions. Studies investigating acute stimulating effects of light on brain activity during the execution of cognitive tasks have suggested that brain activations progress from subcortical regions involved in alertness, such as the thalamus, the hypothalamus, and the brainstem, before reaching cortical regions associated with the ongoing task. In the course of aging, lower blue light sensitivity of some NIF functions has been reported. Here, we first describe neural pathways underlying effects of light on NIF functions and we discuss eye and cerebral mechanisms associated with aging which may affect NIF light sensitivity. Thereafter, we report results of investigations on pupillary constriction and cognitive brain sensitivity to light in the course of aging. Whereas the impact of light on cognitive brain responses appears to decrease substantially, pupillary constriction seems to remain more intact over the lifespan. Altogether, these results demonstrate that aging research should take into account the diversity of the pathways underlying the effects of light on specific NIF functions which may explain their differences in light sensitivity.

Cardiovascular risk profile of patients with peripheral arterial occlusive disease during nilotinib therapy.

BACKGROUND: Over the past few years, data have suggested that severe peripheral arterial occlusive disease (PAOD) is associated with nilotinib exposure. However, the characteristics of this adverse drug reaction are poorly described since its frequency is low. As far as we know, no study using a spontaneous adverse drug reactions reporting system was performed to describe the characteristics of cases of PAOD related to nilotinib. OBJECTIVE: We performed a study to describe the cardiovascular risk profile of cases of PAOD in patients treated with nilotinib spontaneously reported to the French Pharmacovigilance Database (FPVD). PATIENTS/METHODS: We selected all cases of "vascular disorders," as the System Organ Class in MedDRA®, in which nilotinib was "suspected" and recorded in the French Pharmacovigilance Database between 2007 and 21 October 2014. We then identified cases of PAOD with a Low Level Term and through a detailed summary of the clinical description. RESULTS: We identified 25 cases of POAD. Most of the patients were older than 60 years (84 %) or had another cardiovascular risk factor such as hypercholesterolemia, arterial hypertension, overweight/obesity, smoking, or diabetes mellitus (72 %). Females (13 cases) and males (12 cases) were equally represented, but the presence of cardiovascular risk factors was more frequent in females than in males. The mean time from initiation of nilotinib to PAOD onset was 24 months and was significantly longer in patients aged less than 60 years compared with those aged over 60 years (33.8 ± 24.6 months vs. 22.6 ± 17.5 months, p = 0.002). Pre-existing cardiovascular risk factors, especially diabetes mellitus, also seem to accelerate its occurrence. CONCLUSIONS: The FPVD is a useful tool in describing the cardiovascular risk profile of patients with PAOD during nilotinib exposure. Physicians have to be particularly vigilant in patients older than 60 years of age; in patients younger than 60 years of age, long-term surveillance has to be maintained.

Contribution of above- and below-ground plant traits to the structure and function of grassland soil microbial communities.

BACKGROUND AND AIMS: Abiotic properties of soil are known to be major drivers of the microbial community within it. Our understanding of how soil microbial properties are related to the functional structure and diversity of plant communities, however, is limited and largely restricted to above-ground plant traits, with the role of below-ground traits being poorly understood. This study investigated the relative contributions of soil abiotic properties and plant traits, both above-ground and below-ground, to variations in microbial processes involved in grassland nitrogen turnover. METHODS: In mountain grasslands distributed across three European sites, a correlative approach was used to examine the role of a large range of plant functional traits and soil abiotic factors on microbial variables, including gene abundance of nitrifiers and denitrifiers and their potential activities. KEY RESULTS: Direct effects of soil abiotic parameters were found to have the most significant influence on the microbial groups investigated. Indirect pathways via plant functional traits contributed substantially to explaining the relative abundance of fungi and bacteria and gene abundances of the investigated microbial communities, while they explained little of the variance in microbial activities. Gene abundances of nitrifiers and denitrifiers were most strongly related to below-ground plant traits, suggesting that they were the most relevant traits for explaining variation in community structure and abundances of soil microbes involved in nitrification and denitrification. CONCLUSIONS: The results suggest that consideration of plant traits, and especially below-ground traits, increases our ability to describe variation in the abundances and the functional characteristics of microbial communities in grassland soils.

Sleep and wake disturbances following traumatic brain injury.

Traumatic brain injury (TBI) is a major health concern in industrialised countries. Sleep and wake disturbances are among the most persistent and disabling sequelae after TBI. Yet, despite the widespread complaints of post-TBI sleep and wake disturbances, studies on their etiology, pathophysiology, and treatments remain inconclusive. This narrative review aims to summarise the current state of knowledge regarding the nature of sleep and wake disturbances following TBI, both subjective and objective, spanning all levels of severity and phases post-injury. A second goal is to outline the various causes of post-TBI sleep-wake disturbances. Globally, although sleep-wake complaints are reported in all studies and across all levels of severity, consensus regarding the objective nature of these disturbances is not unanimous and varies widely across studies. In order to optimise recovery in TBI survivors, further studies are required to shed light on the complexity and heterogeneity of post-TBI sleep and wake disturbances, and to fully grasp the best timing and approach for intervention.

The minimally invasive MitraClip™ procedure for mitral regurgitation under general anaesthesia: immediate effects on the pulmonary circulation and right ventricular function.

A relatively new minimally invasive cardiological procedure, called the MitraClip(™), does not require sternotomy and may have a number of advantages compared with open mitral valve surgery, but its acute impact on the pulmonary circulation and right ventricular function during general anaesthesia is unclear. We prospectively assessed the effects of the MitraClip procedure in 81 patients with or without pulmonary hypertension (defined as mean pulmonary artery pressure > 25 mmHg), who were anaesthetised using fentanyl (5 µg.kg(-1)), etomidate (0.2-0.3 mg.kg(-1)), rocuronium (0.5-0.6 mg.kg(-1)) and isoflurane. Placement of the MitraClip led to a 60% increase in mean (SD) right ventricular stroke work index (from 512 (321) to 820 (470) mmHg.ml.m(-2), p < 0.0001), while mean (SD) pulmonary vascular resistance index decreased by 24% (522 (330) to 399 (244) dyn.s.cm(-5), p < 0.0001), and mean (SD) pulmonary artery pressure decreased by 10% (30 (8) to 27 (8) mmHg, p < 0.0001). Patients with pulmonary hypertension experienced a similar decrease in mean pulmonary artery pressure compared with those without, and they also had a slight reduction in mean (SD) pulmonary artery occlusion pressure (22 (6) down to 20 (6) mmHg, p = 0.044). We conclude that successful MitraClip treatment for mitral regurgitation acutely improves right ventricular performance by reducing right ventricular afterload, regardless of whether patients have pre-operative pulmonary hypertension.

Structural and functional characterization of enamel pigmentation in shrews.

Pigmented tooth enamel occurs in several vertebrate clades, ranging from mammals to fish. Although an iron compound is associated with this orange to red colored pigmentation, its chemical and structural organization within the enamel is unknown. To determine the nature of the iron compound, we investigated heavily pigmented teeth of the northern short-tailed shrew Blarina brevicauda using combined characterization techniques such as scanning and transmission electron microscopy and synchrotron X-ray diffraction. We found that the pigmentation of the enamel with an iron content of around 8wt% results from a close to amorphous magnetite phase deposited around the nm-sized enamel crystals. Furthermore, the influence of the pigmentation on the enamel hardness was determined by nanoindentation measurements. Finally, the biomechanical function and biological context are discussed in light of the obtained results.

Effects of melatonin and bright light administration on motor and sensory symptoms of RLS.

BACKGROUND: A close temporal relationship was shown between the onset of melatonin secretion at night and the worsening of restless legs syndrome (RLS) symptoms, suggesting that melatonin may play a role in the genesis of this phenomenon. To test this hypothesis we studied the effects of the administration of exogenous melatonin and, conversely, the suppression of endogenous melatonin secretion by bright light exposure on the severity of RLS symptoms. METHODS: Eight RLS subjects were studied in three conditions: at baseline, after administration of melatonin and during bright light exposure. The severity of RLS symptoms was assessed by the suggested immobilization test (SIT), which allows quantification of both sensory and motor manifestations (SIT-PLM) of RLS. RESULTS: Analyses showed a significant increase of SIT-PLM index when subjects received exogenous melatonin compared to both baseline and bright light conditions, but bright light exposure had no effect on leg movements compared to the baseline condition. Analyses also revealed a small but significant decrease in sensory symptoms with bright light exposure compared to baseline. CONCLUSION: Exogenous melatonin may have a detrimental effect on motor symptoms, and bright light exposure produced small but significant improvement of leg discomfort. The study shows the interest of using the SIT to measure outcome of intervention in RLS. Further studies will be needed to assess the therapeutic value of bright light in RLS.

[Teratozoospermia at the time of intracytoplasmic morphologically selected sperm injection (IMSI)]. / La tératozoospermie à l'heure de l'intracytoplasmic morphologically selected sperm injection (IMSI).

Until now, the morphological sperm analysis (spermocytogram) allows to define sperm normality, but the relationship between sperm morphology and fertility is not yet assessed. Although several studies do not report any relationship between abnormal sperm morphology and ICSI results, nevertheless, the success rate of ICSI sems to be dependent on injected sperm morphological aspect. Detailed morphological sperm examination (especially sperm head) at high magnification (from x 6600 to x 12500) (MSOME) in real time allows to select the best spermatozoa before oocyte injection (IMSI). In some cases, implantation and ongoing pregnancy rates were improved with this sperm selection method. Ultramorphologic criteria were established and the most predictive factor of sperm quality is the presence of vacuoles in the sperm head. Those vacuoles appear to be related to DNA damage (fragmentation and/or denaturation) and affect embryo development. To standardize those observations, several authors tried to establish sperm MSOME classifications in order to be used in routine and to replace the conventional spermocytogram in the next future.

The impact of chronic primary insomnia on the heart rate--EEG variability link.

OBJECTIVE: To determine if chronic insomnia alters the relationship between heart rate variability and delta sleep determined at the EEG. METHODS: After one night of accommodation, polysomnography was performed in 14 male patients with chronic primary insomnia matched with 14 healthy men. ECG and EEG recordings allowed the determination of High Frequency (HF) power of RR-interval and delta sleep EEG power across the first three Non Rapid Eye Movement (NREM)-REM cycles. Interaction between normalized HF RR-interval variability and normalized delta sleep EEG power was studied by coherency analysis. RESULTS: Patients showed increased total number of awakenings, longer sleep latency and wake durations and shorter sleep efficiency and REM duration than controls (p<.01). Heart rate variability across first three NREM-REM cycles and sleep stages (NREM, REM and awake) were similar between both groups. In each group, normalized HF variability of RR-interval decreased from NREM to both REM and awake. Patients showed decreased linear relationship between normalized HF RR-interval variability and delta EEG power, expressed by decreased coherence, in comparison to controls (p<.05). Gain and phase shift between these signals were similar between both groups. CONCLUSIONS: Interaction between changes in cardiac autonomic activity and delta power is altered in chronic primary insomniac patients, even in the absence of modifications in heart rate variability and cardiovascular diseases. SIGNIFICANCE: This altered interaction could reflect the first step to cardiovascular disorders.

[Embryo quality and selection]. / Qualité et sélection des embryons.

Embryo quality is routinely evaluated based on morphological and kinematic criteria, but it should also be founded on clinical and biological data from the ovulation induction treatments and the data from the SPZ test, with, if necessary, their genetic analysis. Zygote quality evaluation is based on the zygote score or the P0 profiles. Embryo cleavage kinetics is evaluated at D1 (early cleavage 25-27 h post-insemination), at D2 (four cells), and at D3 (eight cells), and their selection, particularly for eSET, is for the most part based on the cell number and regularity, the percentage of fragmentation (< or = 20 %) and the location of the fragments and the absence of blastomere polynucleation. Imaging software (Fertimorph) now facilitates the evaluation of embryo quality.