UAV-borne LiDAR revolutionizing groundwater level mapping.

In hydrogeological research, the systematic and periodic measurement of the piezometric level is fundamental to assess aquifer storage, identify recharge and discharge areas, define flow directions and to infer the balance between inputs and withdrawals. Furthermore, knowledge of this variable and its fluctuations is essential for the efficient management and protection of groundwater resources. In this work, a novel methodology is proposed for the remote acquisition of piezometric information from traditional large-diameter wells, using drone-borne LiDAR observations. The workflow developed consists of different stages, from flight planning and parameter setting, to point cloud generation, data processing and validation and its statistical treatment to extract piezometric information. This methodology has been applied in a small coastal aquifer with numerous wells that have served as monitoring points. The UAV-LiDAR has enabled the straightforward obtention of measurements of the piezometric level with very high vertical accuracies (RMSE of 5 cm) with minimum and maximum residuals of -8.7 and 7.9 cm respectively. Likewise, the method has shown vertical accuracies 3 times better than those inferred from the official DTM of best resolution available in Spain, which is usually used in hydrogeological works. Since the technique provides absolute values of the piezometric level, it eliminates the need for laborious levelling work prior to hydrogeological campaigns. This method has proved to be an effective alternative/complementary technique to traditional measurements of the piezometric level, allowing to monitor extensive or inaccessible areas over short periods of time and to potentially reduce gaps in hydrogeological databases.

Shaping subcellular tubes through vesicle trafficking: Common and distinct pathways.

Cells with subcellular lumens form some of the most miniature tubes in the tubular organs of animals. These are often crucial components of the system, executing functions at remote body locations. Unlike tubes formed by intercellular or autocellular junctions, the cells with junctionless subcellular lumens face unique challenges in modifying the cell shape and plasma membrane organization to incorporate a membrane-bound tube within, often associated with dramatic cellular growth and extensions. Results in the recent years have shown that membrane dynamics, including both the primary delivery and recycling, is crucial in providing the cell with the flexibility to face these challenges. A significant portion of this information has come from two in vivo invertebrate models; the Drosophila tracheal terminal cells and the C. elegans excretory cell. This review focuses on the data obtained from these systems in the recent past about how trafficking pathways influence subcellular tube and branching morphogenesis. Given that such tubes occur in vertebrate vasculature, these insights are relevant to human health, and we contrast our conclusions with the less understood subcellular tubes of angiogenesis.

The morphometric acclimation to depth explains the long-term resilience of the seagrass Cymodocea nodosa in a shallow tidal lagoon.

Cadiz Bay is a shallow mesotidal lagoon with extensive populations of the seagrass Cymodocea nodosa at intertidal and shallow subtidal elevations. This work aims to understand the mechanisms behind the resilience of this species to gradual sea level rise by studying its acclimation capacity to depth along the shallow littoral, and therefore, to gradual variations in the light environment. To address this objective, these populations have been monitored seasonally over a 10 year period, representing the longest seasonal database available in the literature for this species. The monitoring included populations at 0.4, -0.08 and -0.5 m LAT. The results show that C. nodosa has a strong seasonality for demographic and shoot dynamic properties - with longer shoots and larger growth in summer (high temperature) than in winter (low temperature), but also some losses. Moreover, shoots have different leaf morphometry depending on depth, with small and dense shoots in the intertidal areas (0.4 m) and sparse large shoots in the subtidal ones (-0.08 and 0.5 m). These differences in morphometry and shoot dynamic properties, combined with the differences in shoot density, explain the lack of differences in meadow production balance (i.e. meadow growth - meadow losses) between the intertidal (0.4 m) and the deepest population (-0.5 m), supporting the long term resilience of Cymodocea nodosa in Cadiz Bay. This study contributes to the understanding of the mechanisms behind seagrass stability and resilience, which is particularly important towards predicting the effects of climate change on these key coastal ecosystems, and also highlights the value of continuous long-term monitoring efforts to evaluate seagrass trajectories.

Dosage of anti-PD-1 monoclonal antibodies: a cardinal open question

Discovery and clinical development of monoclonal antibodies with the ability to interfere in the regulation of the immune response have significantly changed the landscape of oncology in recent years. Among the active agents licensed by the regulatory agencies, nivolumab and pembrolizumab are paradigmatic as the most relevant ones according to the magnitude of available data derived from the extensive preclinical and clinical experience. Although in both cases the respective data sheets indicate well-defined dosage regimens, a review of the literature permits to verify the existence of many issues still unresolved about dosing the two agents, so it must be considered an open question of potentially important consequences, in which to work to improve the effectiveness and efficiency of use (AU)

Classification of first-episode psychosis using cortical thickness: A large multicenter MRI study.

Machine learning classifications of first-episode psychosis (FEP) using neuroimaging have predominantly analyzed brain volumes. Some studies examined cortical thickness, but most of them have used parcellation approaches with data from single sites, which limits claims of generalizability. To address these limitations, we conducted a large-scale, multi-site analysis of cortical thickness comparing parcellations and vertex-wise approaches. By leveraging the multi-site nature of the study, we further investigated how different demographical and site-dependent variables affected predictions. Finally, we assessed relationships between predictions and clinical variables. 428 subjects (147 females, mean age 27.14) with FEP and 448 (230 females, mean age 27.06) healthy controls were enrolled in 8 centers by the ClassiFEP group. All subjects underwent a structural MRI and were clinically assessed. Cortical thickness parcellation (68 areas) and full cortical maps (20,484 vertices) were extracted. Linear Support Vector Machine was used for classification within a repeated nested cross-validation framework. Vertex-wise thickness maps outperformed parcellation-based methods with a balanced accuracy of 66.2% and an Area Under the Curve of 72%. By stratifying our sample for MRI scanner, we increased generalizability across sites. Temporal brain areas resulted as the most influential in the classification. The predictive decision scores significantly correlated with age at onset, duration of treatment, and positive symptoms. In conclusion, although far from the threshold of clinical relevance, temporal cortical thickness proved to classify between FEP subjects and healthy individuals. The assessment of site-dependent variables permitted an increase in the across-site generalizability, thus attempting to address an important machine learning limitation.

Dosage of anti-PD-1 monoclonal antibodies: a cardinal open question.

Discovery and clinical development of monoclonal antibodies with the ability to interfere in the regulation of the immune response have significantly changed the landscape of oncology in recent years. Among the active agents licensed by the regulatory agencies, nivolumab and pembrolizumab are paradigmatic as the most relevant ones according to the magnitude of available data derived from the extensive preclinical and clinical experience. Although in both cases the respective data sheets indicate well-defined dosage regimens, a review of the literature permits to verify the existence of many issues still unresolved about dosing the two agents, so it must be considered an open question of potentially important consequences, in which to work to improve the effectiveness and efficiency of use.

R230C but not - 565C/T variant of the ABCA1 gene is associated with type 2 diabetes in Mexicans through an effect on lowering HDL-cholesterol levels.

PURPOSE: Type 2 diabetes (T2D) and low serum concentration of high-density lipoprotein cholesterol (HDL-c) are common coexisting metabolic disorders. ABCA1 variants have been shown to be associated to these conditions. We sought to test the combined effect of two ABCA1 gene common variants, rs2422493 (- 565C > T) and rs9282541 (R230C) on HDL-c levels and T2D risk. METHODS: Path analysis was conducted in 3,303 Mexican-mestizos to assess the specific contributions of rs2422493 and rs9282541 ABCA1 variants, insulin resistance, waist-to-height ratio (WHtR), and age on HDL-c levels and T2D risk. Participants were classified into four groups according to their ABCA1 variants carrier status: (i) the reference group carried wild type alleles for both ABCA1 variants (-/-), (ii) +/- were carriers of rs2422493 but non-carriers of rs9282541, (iii) -/+ for carriers of rs9282541 but not carriers of rs2422493 and (iv) carriers of minor alleles for both SNPs (+/+). Principal components from two previous genome-wide association studies were used to control for ethnicity. RESULTS: We identified significant indirect effects on T2D risk mediated by HDL-c in groups -/+ and +/+ (ß = 0.04; p = 0.03 and ß = 0.06; p < 0.01, respectively) in comparison to the -/- reference group. Low concentrations of HDL-c were directly and significantly associated with increased T2D risk (ß = -0.70; p < 0.01). WHtR, male gender, age, and insulin resistance were also associated with T2D risk (p < 0.05). There was no significant direct effect for any of the ABCA1 groups on T2D risk: p = 0.99, p = 0.58, and p = 0.91 for groups +/-, -/+, and +/+ respectively. CONCLUSIONS: The ABCA1 rs9282541 (R230C) allele is associated with T2D in Mexicans through its effect on lowering HDL-c levels. This is the first report demonstrating that HDL-c levels act as an intermediate factor between an ABCA1 variant and T2D.

Cytotoxic Lesions of the Corpus Callosum Caused by Thermogenic Dietary Supplements.

Consumption of over-the-counter dietary supplements to reduce body weight is common among the population. Thermogenics are herbal combinations that claim to produce a fat-burning process through an increase in the cellular metabolic rate and greater cellular energy consumption, having a high risk for patients developing toxic leukoencephalopathy. We present a series of 6 patients with acute neurologic symptoms and MR imaging showing restricted diffusion and decreased apparent diffusion coefficient values (mean value, 400 mm2/s × 10-6) in the entire corpus callosum compatible with a cytotoxic lesion of the corpus callosum. Although patients responded favorably to the product discontinuation with rapid recovery of neurologic symptoms, there was a more prolonged resolution on imaging alterations. Because of the widespread availability and unregulated nature of thermogenic dietary supplements, physicians must be aware of the clinical and radiologic characteristics of these potential complications of their use.

Health-related quality of life following surgical attenuation of congenital portosystemic shunts versus healthy controls.

OBJECTIVES: To design a health-related quality of life questionnaire for dogs with congenital portosystemic shunts, use it in a cohort of dogs treated with suture attenuation and compare results with those obtained from a healthy control cohort. MATERIALS AND METHODS: Data were collected from the hospital records of dogs treated with suture ligation of an intrahepatic or extrahepatic congenital portosystemic shunt at two referral centres. Owners were asked to complete a questionnaire assessing their dog's health-related quality of life preoperatively (retrospectively) and at the time of follow-up. Owners of control dogs also completed the questionnaire. RESULTS: One hundred and twenty-eight dogs with congenital portosystemic shunts and 131 control dogs were recruited. Median follow-up time was 64 months (range 19.7 to 157.2). The median long-term health-related quality of life score was excellent for both intrahepatic and extrahpatic shunt cases and similar to that of control dogs. The long-term portosystemic shunt clinical sign scores for both intrahepatic and extrahepatic congenital portosystemic shunt dogs were significantly worse than the those of the control group. CLINICAL SIGNIFICANCE: Suture attenuation of congenitial portosystemic shunts is associated with an excellent health-related quality of life score at long-term follow-up.

Evaluating the effect of metronidazole plus amoxicillin-clavulanate versus amoxicillin-clavulanate alone in canine haemorrhagic diarrhoea: a randomised controlled trial in primary care practice.

OBJECTIVES: To investigate the benefit of supplementing amoxicillin-clavulanic acid therapy with metronidazole in dogs presenting to a primary care veterinary practice with severe haemorrhagic diarrhoea. MATERIALS AND METHODS: Prospective randomised blinded trial on dogs presenting with haemorrhagic diarrhoea of less than 3 days duration to a primary care veterinary hospital and also requiring intravenous fluid therapy. Cases were randomised to receive either metronidazole or saline, in addition to standard supportive therapy consisting of amoxicillin-clavulanic acid, intravenous fluid therapy, buprenorphine and omeprazole. Treatment efficacy was measured by duration of hospitalisation and daily scoring of disease severity. RESULTS: Thirty-four cases successfully completed the trial. There was no significant difference in hospitalisation time between treatment groups (mean for dogs receiving metronidazole was 29.6 hours and for controls was 26.3 hours) nor in daily clinical scores. CLINICAL SIGNIFICANCE: This study strongly suggests that addition of metronidazole is not an essential addition to amoxicillin-clavulanic acid therapy for treatment of severe cases of haemorrhagic diarrhoea in dogs.

A concise review of opioid-induced esophageal dysfunction: is this a new clinical entity?

Opioids have become the most widely prescribed analgesics in Western countries. Opioid-induced bowel dysfunction is a widely known adverse effect, with constipation the most common manifestation. Most of the opioid-related effects occur in the stomach, small intestine, and colon and have been widely studied. However, the effects related to esophageal motility are less known. Recently published retrospective studies have suggested that long-term use of opioids can cause esophageal motility dysfunction, reflecting symptoms similar to motility disorders, such as achalasia and functional esophagogastric junction outflow obstruction. The most common manometric findings, as reported in the literature, for patients with opioid-induced dysphagia undergoing long-term therapy with these drugs are impaired lower esophageal sphincter relaxation, high amplitude/velocity, and simultaneous esophageal waves, higher integrated relaxation pressure, lower distal latency, and the esophageal contractility can be normal, hypercontractile, or premature. Based on these studies, a new clinical entity known as opioid-induced esophageal dysfunction has been postulated. For these patients, the diagnostic method of choice is high-resolution manometry, although other causes should be ruled out through endoscopy or Computed Tomography (CT). The best therapeutic option for these patients is withdrawal of the opioid; however, this is not always possible, and other options need to be investigated, such as pneumatic dilation and botulinum toxin injection, considering the risks versus the benefits.

Long-term serum bile acid concentrations in 51 dogs after complete extrahepatic congenital portosystemic shunt ligation.

OBJECTIVES: To report the long-term bile acid stimulation test results for dogs that have undergone complete suture ligation of a single congenital extrahepatic portosystemic shunt. MATERIALS AND METHODS: Data were collected from the hospital records of all dogs that had undergone a complete suture ligation of a single congenital extrahepatic portosystemic shunt. Owners were invited to return to the referral centre or their local veterinarian for repeat serum bile acid measurement. Dogs diagnosed with idiopathic epilepsy and undergoing bile acid stimulation tests were used as a comparison population. RESULTS: Fifty-one study dogs were included, with a mean follow-up time of 62 months. 48 dogs had no evidence of multiple acquired shunts and a significant reduction in the pre- and post-prandial serum bile acid concentrations at long-term follow-up compared with pre-operative measurements. Pre- and post-prandial serum bile acids were statistically significantly greater for dogs that had undergone a full ligation (with no evidence of multiple acquired shunts) at all time points compared to the control dogs (P<0·001 for all comparisons). CLINICAL SIGNIFICANCE: The results suggest that in dogs treated with complete suture ligation mild increases in serum bile acids are not clinically relevant if there are no physical examination abnormalities, a normal body condition score and no relapse in clinical signs.

Manejo del edema pulmonar agudo cardiogénico en el servicio de urgencia / Review of Acute Cardiogenic Pulmonary Edema Management in the Emergency Department

El Edema Pulmonar Agudo Cardiogénico es un cuadro clínico frecuente en los servicios de urgencia y conlleva una alta mortalidad, y junto a otras complicaciones de la insuficiencia cardíaca podría continuar incrementándose con los años. Los avances en la evaluación y el manejo de esta patología en el Servicio de Urgencia se centran en la utilidad de la ultrasonografía al lado del paciente, en la utilización apropiada de la farmacoterapia existente y la aplicación de herramientas de soporte ventilatorio que anticipen y eviten la necesidad de intubación oro-traqueal y ventilación mecánica.

Acute cardiogenic pulmonary edema is a medical condition often seen in the emergency department. It has high mortality and, as with other complications of heart failure, its incidence may continue to rise in the future. Advances in the evaluation and management of this pathology in the emergency department focus on the benefit of bedside ultrasound, the appropriate use of existing pharmacotherapy and the use of ventilation support equipment that anticipate and avert the need for orotracheal intubation and mechanical ventilation.

Manejo del edema pulmonar agudo cardiogénico en el servicio de urgencia / Management of acute cardiogenic pulmonary edema in an emergency service

El Edema Pulmonar Agudo Cardiogénico es un cuadro clínico frecuente en los servicios de urgencia y conlleva una alta mortalidad, y junto a otras complicaciones de la insuficiencia cardíaca podría continuar incrementándose con los años. Los avances en la evaluación y el manejo de esta patología en el Servicio de Urgencia se centran en la utilidad de la ultrasonografía al lado del paciente, en la utilización apropiada de la farmacoterapia existente y la aplicación de herramientas de soporte ventilatorio que anticipen y eviten la necesidad de intubación oro-traqueal y ventilación mecánica.

Acute cardiogenic pulmonary edema is frequently seen in the emergency services and has a high mortality and, as with other complications of heart failure, it may increase over the years. Advances in its evaluation and management in the emergency services are centered on bedside ultrasonography, appropriate use of available drugs and early ventilation support that anticipates and avoids the need for endotracheal intubation and mechanical ventilation.

Effect of hydroxytyrosol on quality of sulfur dioxide-free red wine.

In this work, the feasibility of two commercial products enriched in hydroxytyrosol (HT) as alternative to sulfur dioxide in Syrah red wines was evaluated. The HT enriched products came from synthesis and from olive waste. Wines treated with HT were compared with wines treated with sulfur dioxide at two winemaking stages: bottling and after 6 months of storage in bottle. Minor differences were found in enological parameters and volatile composition (esters, alcohols and acids). Significant differences were observed in color related parameters and sensory analysis. HT wines improved color parameters as well as scents and tasting at bottling. However, after 6 months of storage in bottle HT wines were more oxidized than SO2 wines. The olfactometry profile of HT wines supported sensory analysis. HT wines showed new odorant zones from both the added product and oxidation.

Onlay foreskin flap anastomosed directly to the tunica albuginea: a short-term experimental study in rabbits.

INTRODUCTION: In severe hypospadias, urethral plate division is necessary for curvature correction. To configure the new urethra, an approach has been described using a foreskin flap directly anastomosed in an 'onlay' fashion to the tunica albuginea of the corpora cavernosa. Results suggest that it is possible to use the corpus cavernosum albuginea as the posterior wall of the neourethra without the need of a dorsal graft. OBJECTIVE: The present experimental study aimed to evaluate the histological characteristics and healing pattern of this procedure. STUDY DESIGN: Sixteen New Zealand male rabbits were divided into two groups of eight animals. Eight animals underwent 1-cm longitudinal dorsal incision of the penile urethra and the edges were anastomosed to the tunica albuginea (Group 1). Eight other animals underwent complete excision of 1.0 cm of penile urethra. Urethroplasty was performed using a foreskin flap directly anastomosed as an onlay to the albuginea, as shown in the figure (Group 2). Sacrifice and histological assessment was performed 2, 4, 8 and 12 weeks postoperatively. RESULTS: In Group 1, a mild inflammatory process was noted that became almost imperceptible at 12 weeks. Fibrosis was mild at all stages in this group. Over time, a regenerative epithelium covered the corpus cavernosum. Immunohistochemistry using specific CK-7 and CK-20 confirmed the presence of urothelium. No complications were microscopically detected in this group. Group 2 presented with a more intense inflammatory infiltrate, which also resolved over time. Fibrosis was slightly more intense in this group, especially in animals that had urethral strictures. Group 2 presented with three fistulas, two were associated with urethral stricture. Histological evaluation showed the presence of epithelization over the albuginea, which turned out to be similar to the normal urothelium over time and was confirmed by immunohistochemistry. Non-keratinized stratified squamous epithelium of the foreskin flap showed good integration to the urethra. DISCUSSION: Microscopic analysis showed that inflammation, fibrosis and complications were similar to previous studies. At 12 weeks there was a well-developed epithelium similar to normal urethra, which was confirmed by immunohistochemistry; this was similar to what occurs in the TIP technique, as previously demonstrated. It was hypothesized that the epithelium regeneration developed from the urethral edges, as demonstrated in other experimental studies. CONCLUSION: The albuginea was covered by mature urothelium after 12 weeks, which presumably grew from the urethral edges. The foreskin flap onlay that was directly anastomosed to the albuginea completely integrated and constituted the roof of the neourethra.

A cis-acting element in the promoter of human ether à go-go 1 potassium channel gene mediates repression by calcitriol in human cervical cancer cells.

The human ether à go-go 1 potassium channel (hEAG1) is required for cell cycle progression and proliferation of cancer cells. Inhibitors of hEAG1 activity and expression represent potential therapeutic drugs in cancer. Previously, we have shown that hEAG1 expression is downregulated by calcitriol in a variety of cancer cells. Herein, we provided evidence on the regulatory mechanism involved in such repressive effect in cells derived from human cervical cancer. Our results indicate that repression by calcitriol occurs at the transcriptional level and involves a functional negative vitamin D response element (nVDRE) E-box type in the hEAG1 promoter. The described mechanism in this work implies that a protein complex formed by the vitamin D receptor-interacting repressor, the vitamin D receptor, the retinoid X receptor, and the Williams syndrome transcription factor interact with the nVDRE in the hEAG1 promoter in the absence of ligand. Interestingly, all of these transcription factors except the vitamin D receptor-interacting repressor are displaced from hEAG1 promoter in the presence of calcitriol. Our results provide novel mechanistic insights into calcitriol mode of action in repressing hEAG1 gene expression.

Evaluation of esophagogastric junction relaxation by 4-second Integrated Relaxation Pressure in achalasia using High Resolution Manometry with water-perfused catheters.

BACKGROUND: Relaxation of the esophagogastric junction (EGJ) is now evaluated calculating 4-second integrated relaxation pressure (4-s IRP) by high resolution manometry (HREPT). Solid-state catheters have been used to define abnormal values. Our aim was to evaluate 4-s IRP in esophageal achalasia using HREPT with perfused catheters. METHODS: From June 2009 to June 2013, 936 HREPT studies have been performed in our unit. Of these, 194 patients having treated achalasia were excluded. Control group was constituted by 695 patients without achalasia, and 47 patients with untreated achalasia constituted the study group. HREPT was performed with water-perfused catheters. To establish the cut-off value for 4-s IRP that better discriminate patients with achalasia from all other patients, a receiver operating characteristic (ROC) analysis was performed. KEY RESULTS: Twenty three of 47 achalasia patients (49%) showed a 4-s IRP under 15 mmHg; and seven (15%) had a value under modified Chicago criteria. A cut-off value for 4-s IRP of 6.5 mmHg, calculated by ROC analysis, highly discriminates achalasia from the rest of the patients and especially from scleroderma patients (area under the curve: 0.997, 95% CI: 0.995-1.000; p < 0.001). CONCLUSIONS & INFERENCES: Cut-off values for 4-s IRP defined using HREPT with solid-state catheters are not adequate for diagnosing esophageal achalasia with water-perfused systems. A lower value, i.e., 6.5 mmHg, is suggested for this equipment. The diagnostic criteria of esophageal achalasia should be modified for HREPT performed with water-perfused systems.