Active Control of Alfvén Eigenmodes by Externally Applied 3D Magnetic Perturbations.

The suppression and excitation of Alfvén eigenmodes have been experimentally obtained, for the first time, by means of externally applied 3D perturbative fields with different spatial spectra in a tokamak plasma. The applied perturbation causes an internal fast-ion redistribution that modifies the phase-space gradients responsible for driving the modes, determining, ultimately their existence. Hybrid kinetic-magnetohydrodynamic simulations reveal an edge resonant transport layer activated by the 3D perturbative field as the responsible mechanism for the fast-ion redistribution. The results presented here may help to control fast-ion driven Alfvénic instabilities in future burning plasmas with a significant fusion born alpha particle population.

The Bradyrhizobium Sp. LmicA16 Type VI Secretion System Is Required for Efficient Nodulation of Lupinus Spp.

Many bacteria of the genus Bradyrhizobium are capable of inducing nodules in legumes. In this work, the importance of a type VI secretion system (T6SS) in a symbiotic strain of the genus Bradyrhizobium is described. T6SS of Bradyrhizobium sp. LmicA16 (A16) is necessary for efficient nodulation with Lupinus micranthus and Lupinus angustifolius. A mutant in the gene vgrG, coding for a component of the T6SS nanostructure, induced less nodules and smaller plants than the wild-type (wt) strain and was less competitive when co-inoculated with the wt strain. A16 T6SS genes are organized in a 26-kb DNA region in two divergent gene clusters of nine genes each. One of these genes codes for a protein (Tsb1) of unknown function but containing a methyltransferase domain. A tsb1 mutant showed an intermediate symbiotic phenotype regarding vgrG mutant and higher mucoidity than the wt strain in free-living conditions. T6SS promoter fusions to the lacZ reporter indicate expression in nodules but not in free-living cells grown in different media and conditions. The analysis of nodule structure revealed that the level of nodule colonization was significantly reduced in the mutants with respect to the wt strain.

Time-dependent cognitive and somatic symptoms of depression as predictors of new cardiac-related events in at-risk patients: the UPBEAT-UK cohort.

BACKGROUND: Evidence suggests that somatic rather than cognitive depressive symptoms are risk factors for recurrent cardiac events in at-risk patients. However, this has never been explored using a time-dependent approach in a narrow time-frame, allowing a cardiac event-free time-window. METHODS: The analysis was performed on 595 participants [70.6% male, median age 72 (27-98)] drawn from the UPBEAT-UK heart disease patient cohort with 6-monthly follow-ups over 3 years. Depressive symptomatology was measured using the Patient Health Questionnaire-9 (PHQ-9) (four somatic, five cognitive items). New cardiac events (NCEs) including cardiac-related mortality were identified by expert examination of patient records. Analyses were performed using Cox proportional hazard models with delayed entry, with time-dependent depressive dimensions and covariates measured 12-18 months (median: 14.1, IQR: 3.5) prior to the event, with a 12-month cardiac event-free gap. RESULTS: There were 95 NCEs during the follow-up [median time-to-event from baseline: 22.3 months (IQR: 13.4)]. Both the somatic (HR 1.12, 95% CI 1.05-1.20, p = 0.001) and cognitive dimensions (HR 1.11, 95% CI 1.03-1.18, p = 0.004) were time-dependent risk factors for an NCE in the multi-adjusted models. Specific symptoms (poor appetite/overeating for the somatic dimension, hopelessness and feeling like a failure for the cognitive dimension) were also significantly associated. CONCLUSION: This is the first study of the association between depressive symptom dimensions and NCEs in at-risk patients using a time-to-event standardised approach. Both dimensions considered apart were independent predictors of an NCE, along with specific items, suggesting regular assessments and tailored interventions targeting specific depressive symptoms may help to prevent NCEs in at-risk populations.

Multi-scale modeling of 2D GaSe FETs with strained channels.

Electronic devices based on bidimensional materials (2DMs) are the subject of an intense experimental research, that demands a tantamount theoretical activity. The latter must be hold up by a varied set of tools able to rationalize, explain and predict the operation principles of the devices. However, in the broad context of multi-scale computational nanoelectronics, there is currently a lack of simulation tools connecting atomistic descriptions with semi-classical mesoscopic device-level simulations and able to properly explain the performance of many state-of-the-art devices. To contribute to filling this gap we present a multi-scale approach that combines fine-level material calculations with a semi-classical drift-diffusion transport model. Its use is exemplified by assessing 2DM field effect transistors with strained channels, showing excellent capabilities to capture the changes in the crystal structure and their impact into the device performance. Interestingly, we verify the capacity of strain in monolayer GaSe to enhance the conduction of one type of carrier, enabling the possibility to mimic the effect of chemical doping on 2D materials. These results illustrate the great potential of the proposed approach to bridge levels of abstraction rarely connected before and thus contribute to the theoretical modeling of state-of-the-art 2DM-based devices.

Cross-cultural adaptation and validation of the neurogenic bladder symptom score for Spanish speakers.

AIM: To perform a cross-cultural adaptation and validation of the Neurogenic Bladder Symptom Score (NBSS) to Spanish in patients with neurogenic lower urinary tract dysfunction. MATERIALS AND METHODS: The questionnaire was culturally adapted according to international guidelines. It was applied, twice in a range of 14-28 days. Psychometric properties were tested such as content validity, construct validity, internal consistency, and test-retest reliability. RESULTS: A total of 82 patients between 18 and 78 years old (mean age of 43.9) participated in the study, and completed the first NBSS assessment; only 39 (32.19%) performed the test-retest study. The internal consistency was tested by Cronbach α with a result of 0.86 (95% CI, 0.81-0.90). The reliability was tested by interclass correlation coefficient with a result of 0.91 [0.87-0.95] (p < 0.0001). The construct validity was tested by Pearson correlation between NBSS and Qualiveen-SF, which showed a moderate correlation with a result of 0.57 (p < 0.0001). One-way analysis of variance with trend analysis demonstrated that patients who reported having a more severe problem with their bladder function had a higher NBSS total score (p < 0.001). CONCLUSION: The results of this study demonstrated that the Spanish version of the NBSS has a good internal consistency and reliability, proving its applicability.

[Effects of the COVID-19 pandemic on a cohort of patients with vein occlusion]. / Efectos de la pandemia por SARS-CoV-2 en una cohorte de pacientes con obstrucción venosa retiniana.

BACKGROUND AND OBJECTIVES: A new coronavirus disease in humans, COVID-19, caused by SARS-CoV-2, emerged in December 2019. It has been associated with the development of thrombotic phenomena. Retinal vein occlusion (RVO) is mainly a consequence of vascular risk factors (VRF). This study aimed to analyze cases of COVID-19 in a cohort of patients with RVO (Valdecilla cohort). PATIENTS AND METHODS: Between December 2008 and December 2020, 429 patients with RVO were attended to in our clinic. Ten patients had COVID-19, one of which did not have VRF or thrombophilia. The remaining nine patients had RVO prior to the infection and VRF, six had carotid atherosclerosis, and four had antiphospholipid syndrome. The infection did not cause thrombotic phenomena in any of them. CONCLUSIONS: RVO is a rare manifestation of COVID-19. In our cohort of patients with RVO, COVID-19 disease did not lead to thrombotic events.

Quenching of Exciton Recombination in Strained Two-Dimensional Monochalcogenides.

We predict that long-lived excitons with very large binding energies can also exist in a single or few layers of monochalcogenides such as GaSe. Our theoretical study shows that excitons confined by a radial local strain field are unable to recombine despite electrons and holes coexisting in space. The localized single-particle states are calculated in the envelope function approximation based on a three-band k·p Hamiltonian obtained from density-functional-theory calculations. The binding energy and the decay rate of the exciton ground state are computed after including correlations in the basis of electron-hole pairs. The interplay between the localized strain and the caldera-type valence band characteristic of few-layered monochalcogenides creates localized electron and hole states with very different quantum numbers which hinders the recombination even for singlet excitons.

Laser-Beam-Patterned Topological Insulating States on Thin Semiconducting MoS_{2}.

Identifying the two-dimensional (2D) topological insulating (TI) state in new materials and its control are crucial aspects towards the development of voltage-controlled spintronic devices with low-power dissipation. Members of the 2D transition metal dichalcogenides have been recently predicted and experimentally reported as a new class of 2D TI materials, but in most cases edge conduction seems fragile and limited to the monolayer phase fabricated on specified substrates. Here, we realize the controlled patterning of the 1T^{'} phase embedded into the 2H phase of thin semiconducting molybdenum-disulfide by laser beam irradiation. Integer fractions of the quantum of resistance, the dependence on laser-irradiation conditions, magnetic field, and temperature, as well as the bulk gap observation by scanning tunneling spectroscopy and theoretical calculations indicate the presence of the quantum spin Hall phase in our patterned 1T^{'} phases.

Ultrasound as a diagnostic and management tool in hidradenitis suppurativa patients: a multicentre study.

BACKGROUND: It has been reported that clinical evaluation consistently underestimates the severity of hidradenitis suppurativa (HS). OBJECTIVE: To determine the usefulness of ultrasound as a diagnostic tool in HS compared with clinical examination and to assess the subsequent modification of disease management. METHODS: Cross-sectional multicentre study. Severity classification and therapeutic approach according to clinical vs. ultrasound examination were compared. RESULTS: Of 143 HS patients were included. Clinical examination scored 38, 70 and 35 patients as Hurley stage I, II and III, respectively; with ultrasound examination, 21, 80 and 42 patients were staged with Hurley stage I, II and III disease, respectively (P < 0.01). In patients with stage I classification as determined by clinical examination, 44.7% changed to a more severe stage. Clinical examination indicated that 44.1%, 54.5% and 1.4% of patients would maintain, increase or decrease treatment, respectively. For ultrasound examination, these percentages were 31.5%, 67.1% and 1.4% (P < 0.01). Concordance between clinical and ultrasound intra-rater examination was 22.8% (P < 0.01); intra-rater and inter-rater (radiologist) ultrasound agreement was 94.9% and 81.7%, respectively (P < 0.01). LIMITATIONS: The inability to detect lesions that measure ≤0.1 mm or with only epidermal location. CONCLUSION: Ultrasound can modify the clinical staging and therapeutic management in HS by detecting subclinical disease.

Modified SureSelectQXT Target Enrichment Protocol for Illumina Multiplexed Sequencing of FFPE Samples.

BACKGROUND: Personalised medicine is nowadays a major objective in oncology. Molecular characterization of tumours through NGS offers the possibility to find possible therapeutic targets in a time- and cost-effective way. However, the low quality and complexity of FFPE DNA samples bring a series of disadvantages for massive parallel sequencing techniques compared to high-quality DNA samples (from blood cells, cell cultures, etc.). RESULTS: We performed several experiments to understand the behaviour of FFPE DNA samples during the construction of SureSelectQXT libraries. First, we designed a quality checkpoint for FFPE DNA samples based on the quantification of their amplification capability (qcPCR). We observed that FFPE DNA samples can be classified according to DIN value and qcPCR concentration into unusable, or low-quality (LQ) and good-quality (GQ) DNA. For GQ samples, we increased the amount of input DNA to 150 ng and the digestion time to 30 min, whereas for LQ samples, we used 50 ng of DNA as input but we decreased the digestion time to 1 min. In all cases, we increased the cycles of the pre-hyb PCR to 10 but decreased the cycles of the post-hyb PCR to 8. In addition, we confirmed that using half of the volume of reagents can be beneficial. Finally, in order to obtain better results, we designed a decision flow-chart to achieve a seeding concentration of 12-14 pM for MiSeq Reagent Kit v2. CONCLUSIONS: Our experiments allowed us to unveil the behaviour of low-quality FFPE DNA samples during the construction of SureSelectQXT libraries. Sequencing results showed that, using our modified SureSelectQXT protocol, the final percentage of usable reads for low-quality samples was increased more than three times allowing to reach median depth/million reads values of 76.35. This value is equivalent to ~ 0.9 and ~ 0.7 of the values obtained for good-quality FFPE and high-quality DNA respectively.

Graphene flakes obtained by local electro-exfoliation of graphite with a STM tip.

Graphite surfaces can be manipulated by several methods to create graphene structures of different shapes and sizes. Scanning tunneling microscopy (STM) can be used to create these structures either through mechanical contact between the tip and the surface or through electro-exfoliation. In the latter, the mechanisms involved in the process of exfoliation at an applied voltage are not fully understood. Here, we show how a graphite surface can be locally exfoliated in a systematic manner by applying an electrostatic force with a STM tip at the edge of a terrace, forming triangular flakes several nanometers in length. We demonstrate, through experiments and simulations, how these flakes are created by a two-step process: first a voltage ramp must be applied at the edge of the terrace, and then the tip must be scanned perpendicular to the edge. Ab initio electrostatic calculations reveal that the presence of charges on the graphite surface weakens the interaction between layers allowing for exfoliation at voltages in the same range as those used experimentally. Molecular dynamics simulations show that a force applied locally on the edge of a step produces triangular flakes such as those observed under STM. Our results provide new insights into surface modification that can be extended to other layered materials.

A child with resistant Kawasaki disease successfully treated with anakinra: a case report.

BACKGROUND: Kawasaki disease (KD) is an acute self-limited systemic vasculitis of unknown etiology. Intravenous immunoglobulin (IVIG) is an effective treatment and decreases the risk of cardiac complications to less than 5%. In spite of its effectiveness, some children do not respond to this therapy and still develop coronary aneurysms (CAA). The optimal treatment for IVIG non-responsive patients remains controversial although corticoids have been suggested to be an effective treatment in some patients. For those patients still resistant to IVIG and corticoids, interleukin-1 receptor antagonists (IL-1RA) such anakinra could be an alternative. CASE PRESENTATION: We present a 3 year-old Caucasian patient with KD without cardiac complications but with important resistance to treatment. After becoming resistant to IVIG and corticoids, anakinra proved to be an effective treatment. CONCLUSIONS: To our knowledge, this is the first report of the utility of IL-1RA in refractory KD without coronary impairment. The patient fulfilled the classical criteria for KD and, after becoming resistant to first and second line treatments, anakinra proved to be an effective treatment. Further studies are required to determine if this is an effective treatment option for other cases of resistant Kawasaki disease.

Neuroanatomic and behavioral correlates of urinary dysfunction induced by vaginal distension in rats.

The aim of the present study was to use a model of simulated human childbirth in rats to determine the damage to genitourinary structures and behavioral signs of urinary dysfunction induced by vaginal distension (VD) in female rats. In experiment 1, the length of the genitourinary tract and the nerves associated with it were measured immediately after simulated human delivery induced by VD or sham (SH) procedures. Electroneurograms of the dorsal nerve of the clitoris (DNC) were also recorded. In experiment 2, histological characteristics of the bladder and major pelvic ganglion of VD and SH rats were evaluated. In experiment 3, urinary parameters were determined in conscious animals during 6 h of dark and 6 h of light before and 3 days after VD or SH procedures. VD significantly increased distal vagina width (P < 0.001) and the length of the motor branch of the sacral plexus (P < 0.05), DNC (P < 0.05), and vesical nerves (P < 0.01) and decreased DNC frequency and amplitude of firing. VD occluded the pelvic urethra, inducing urinary retention, hematomas in the bladder, and thinness of the epithelial (P < 0.05) and detrusor (P < 0.01) layers of the bladder. Major pelvic ganglion parameters were not modified after VD. Rats dripped urine in unusual places to void, without the stereotyped behavior of micturition after VD. The neuroanatomic injuries after VD occur alongside behavioral signs of urinary incontinence as determined by a new behavioral tool for assessing micturition in conscious animals.

Evidence for effective interventions to reduce mental health-related stigma and discrimination in the medium and long term: systematic review.

BACKGROUND: Most research on interventions to counter stigma and discrimination has focused on short-term outcomes and has been conducted in high-income settings. AIMS: To synthesise what is known globally about effective interventions to reduce mental illness-based stigma and discrimination, in relation first to effectiveness in the medium and long term (minimum 4 weeks), and second to interventions in low- and middle-income countries (LMICs). METHOD: We searched six databases from 1980 to 2013 and conducted a multi-language Google search for quantitative studies addressing the research questions. Effect sizes were calculated from eligible studies where possible, and narrative syntheses conducted. Subgroup analysis compared interventions with and without social contact. RESULTS: Eighty studies (n = 422 653) were included in the review. For studies with medium or long-term follow-up (72, of which 21 had calculable effect sizes) median standardised mean differences were 0.54 for knowledge and -0.26 for stigmatising attitudes. Those containing social contact (direct or indirect) were not more effective than those without. The 11 LMIC studies were all from middle-income countries. Effect sizes were rarely calculable for behavioural outcomes or in LMIC studies. CONCLUSIONS: There is modest evidence for the effectiveness of anti-stigma interventions beyond 4 weeks follow-up in terms of increasing knowledge and reducing stigmatising attitudes. Evidence does not support the view that social contact is the more effective type of intervention for improving attitudes in the medium to long term. Methodologically strong research is needed on which to base decisions on investment in stigma-reducing interventions.

[Ultrasound examination of hidradenitis suppurativa]. / Ecografía de la hidradenitis supurativa.

Hidradenitis suppurativa is a debilitating chronic, recurrent, inflammatory cutaneous disease of the hair follicle that usually presents with painful, deep and inflamed lesions in the areas of the body with apocrine glands, most frequently the axillary, groin and anogenital regions. This entity is difficult to manage since it can be difficult to determine the true nature and extension of the lesions. Cutaneous ultrasound allows real-time visualization of the cutaneous structures under examination, defining the type of lesion, its anatomical extension, and the degree of inflammatory activity, which affects adequate patient management. The present review analyses the importance of ultrasound in the assessment of patients with hidradenitis suppurativa.

[Ultrasound in the management of inflammatory dermatosis]. / Ecografía aplicada al manejo de las dermatosis inflamatorias.

Cutaneous ultrasound is a dermatological diagnostic imaging technique based on the interaction of high-frequency ultrasounds with the skin. Because it is non-invasive, rapid and accessible, it has increasingly wide clinical applications. This article reviews its use in the management of inflammatory dermatological diseases.

DNA copy number profiling reveals extensive genomic loss in hereditary BRCA1 and BRCA2 ovarian carcinomas.

BACKGROUND: Few studies have attempted to characterise genomic changes occurring in hereditary epithelial ovarian carcinomas (EOCs) and inconsistent results have been obtained. Given the relevance of DNA copy number alterations in ovarian oncogenesis and growing clinical implications of the BRCA-gene status, we aimed to characterise the genomic profiles of hereditary and sporadic ovarian tumours. METHODS: High-resolution array Comparative Genomic Hybridisation profiling of 53 familial (21 BRCA1, 6 BRCA2 and 26 non-BRCA1/2) and 15 sporadic tumours in combination with supervised and unsupervised analysis was used to define common and/or specific copy number features. RESULTS: Unsupervised hierarchical clustering did not stratify tumours according to their familial or sporadic condition or to their BRCA1/2 mutation status. Common recurrent changes, spanning genes potentially fundamental for ovarian carcinogenesis, regardless of BRCA mutations, and several candidate subtype-specific events were defined. Despite similarities, greater contribution of losses was revealed to be a hallmark of BRCA1 and BRCA2 tumours. CONCLUSION: Somatic alterations occurring in the development of familial EOCs do not differ substantially from the ones occurring in sporadic carcinomas. However, some specific features like extensive genomic loss observed in BRCA1/2 tumours may be of clinical relevance helping to identify BRCA-related patients likely to respond to PARP inhibitors.

Functional and expression analysis of the metal-inducible dmeRF system from Rhizobium leguminosarum bv. viciae.

A gene encoding a homolog to the cation diffusion facilitator protein DmeF from Cupriavidus metallidurans has been identified in the genome of Rhizobium leguminosarum UPM791. The R. leguminosarum dmeF gene is located downstream of an open reading frame (designated dmeR) encoding a protein homologous to the nickel- and cobalt-responsive transcriptional regulator RcnR from Escherichia coli. Analysis of gene expression showed that the R. leguminosarum dmeRF genes are organized as a transcriptional unit whose expression is strongly induced by nickel and cobalt ions, likely by alleviating the repressor activity of DmeR on dmeRF transcription. An R. leguminosarum dmeRF mutant strain displayed increased sensitivity to Co(II) and Ni(II), whereas no alterations of its resistance to Cd(II), Cu(II), or Zn(II) were observed. A decrease of symbiotic performance was observed when pea plants inoculated with an R. leguminosarum dmeRF deletion mutant strain were grown in the presence of high concentrations of nickel and cobalt. The same mutant induced significantly lower activity levels of NiFe hydrogenase in microaerobic cultures. These results indicate that the R. leguminosarum DmeRF system is a metal-responsive efflux mechanism acting as a key element for metal homeostasis in R. leguminosarum under free-living and symbiotic conditions. The presence of similar dmeRF gene clusters in other Rhizobiaceae suggests that the dmeRF system is a conserved mechanism for metal tolerance in legume endosymbiotic bacteria.