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Background and Purpose Although onset-to-treatment time is associated with early clinical recovery in acute ischemic stroke (AIS) patients treated with intravenous tissue plasminogen activator (tPA), the effect of the timing of tPA-induced recanalization on functional outcomes remains debatable. Methods We conducted a multicenter, prospective observational cohort study to determine whether early (within 1-hour from tPA-bolus) complete or partial recanalization assessed during 2-hour real-time transcranial Doppler monitoring is associated with improved outcomes in patients with proximal occlusions. Outcome events included dramatic clinical recovery (DCR) within 2 and 24-hours from tPA-bolus, 3-month mortality, favorable functional outcome (FFO) and functional independence (FI) defined as modified Rankin Scale (mRS) scores of 0–1 and 0–2 respectively. Results We enrolled 480 AIS patients (mean age 66±15 years, 60% men, baseline National Institutes of Health Stroke Scale score 15). Patients with early recanalization (53%) had significantly (jos-2019-01648P

Abstract Background Study aimed to characterise treatment and outcomes for patients with hormone receptor positive (HR+), human epidermal growth factor 2 negative (HER2-) metastatic breast cancer (MBC) within a large regional cancer centre, as a benchmark for evaluating real-world impact of novel therapies. Methods Retrospective longitudinal cohort, using electronic patient records of adult females with a first diagnosis of HR+/HER2- MBC January 2012–March 2018. Results One hundred ninety-six women were identified with HR+/HER2- MBC. Median age was 67 years, 85.2% were post-menopausal and median time between primary diagnosis and metastasis was 5.4 years. Most (75.1%) patients received endocrine therapy as first line systemic treatment (1st LoT); use of 1st LoT chemotherapy halved between 2012 and 2017. Patients receiving 1st LoT chemotherapy were younger and more likely to have visceral metastasis (p

This paper presents a comprehensive multiwavelength investigation of the intermediate-age open cluster NGC 1912. We identified 401 member stars for NGC 1912 using K-nearest neighbour and Gaussian Mixture Model machine learning techniques. The fundamental parameters determined for the cluster are metallicity (z) = 0.0141 |$\pm$| 0.0006, log(age) = 8.519 |$\pm$| 0.040, binary fraction (⁠|$b_{\text{frac}}$|⁠) = 0.445 |$\pm$| 0.035, visual extinction (⁠|$A_V$|⁠) = 0.864 |$\pm$| 0.033 mag, total-to-selective extinction ratio (⁠|$R_V$|⁠) = 3.007 |$\pm$| 0.096, distance = 1096 |$\pm$| 15 pc. The central density (⁠|$\rho _o$|⁠), core radius (⁠|$r_c$|⁠), tidal radius (⁠|$r_t$|⁠), and background density (⁠|$\rho _{\mathrm{bg}}$|⁠) for the cluster are obtained as 0.643 |$\pm$| 0.067 stars arcmin |$^{-2}$| , 7.743 |$\pm$| 0.784 arcmin, 84.633 |$\pm$| 7.188 arcmin, and 0.001 |$\pm$| 0.000 stars arcmin |$^{-2}$| , respectively. Dynamical mass segregation study revealed a concentration of some apparently massive stars towards the cluster centre. Polarimetric analysis of 90 stars in |$BVR_cI_c$| wavelength bands revealed that the observed polarization in NGC 1912 is not solely attributed to interstellar dust. The Galactic magnetic field is dominant in this region. Dust grain sizes within the intracluster region are found to be relatively smaller than that of the general ISM. The extinction map revealed the existence of a potential 'interstellar bubble' located close to the cluster region. Towards the periphery of the probable bubble region, which displays an ovoid-like geometry, 16 probable young stellar objects have been detected, suggesting the ongoing triggering of secondary star formation events in this region. [ABSTRACT FROM AUTHOR]

Social media has credence value for a brand, and one way a firm might provide cues to consumers is through design elements on its website. A second way a firm might signal its social presence is to expose customers to testimonials about a social media experience with the company. Findings from two studies examining these two tactics demonstrate that positive social media cues lead to favorable perceptions of a brand's warmth and competence. Implications for managing consumers' snap judgments through strategic social media cues are offered. [ABSTRACT FROM AUTHOR]

Abstract Aggregation of alpha-synuclein (α-SYN) is the pathological hallmark of several diseases named synucleinopathies, including Parkinson’s disease (PD), which is the most common neurodegenerative motor disorder. Alpha-SYN has been linked to synaptic function both in physiological and pathological conditions. However, the exact link between neuronal activity, α-SYN toxicity and disease progression in PD is not clear. In this study, we aimed to investigate the effect of chronic neuromodulation in an α-SYN-based rat model for PD using chemogenetics. To do this, we expressed excitatory Designer Receptors Exclusively Activated by Designer Drugs (DREADDs) combined with mutant A53T α-SYN, using two different recombinant adeno-associated viral (rAAV) vectors (serotypes 2/7 and 2/8) in rat substantia nigra (SN) and investigated the effect on motor behavior, synapses and neuropathology. We found that chronic neuromodulation aggravates motor deficits induced by α-SYN, without altering dopaminergic neurodegeneration. In addition, neuronal activation led to changes in post-translational modification and subcellular localization of α-SYN, linking neuronal activity to the pathophysiological role of α-SYN in PD.

Unlike general anaesthesia, neuraxial anaesthesia (NA) reduces the burden and risk of respiratory adverse events in the post-operative period. However, both patients affected by chronic obstructive pulmonary disease (COPD) and chest wall disorders and/or neuromuscular diseases may experience the development or the worsening of respiratory failure, even during surgery performed under NA; this latter negatively affects the function of accessory respiratory muscles, resulting in a blunted central response to hypercapnia and possibly in an exacerbation of cardiac dysfunction (NA-induced relative hypovolemia). According to European Respiratory Society (ERS) and American Thoracic Society (ATS) guidelines, non-invasive ventilation (NIV) is effective in the post-operative period for the treatment of both impaired pulmonary gas exchange and ventilation, while the intra-operative use of NIV in association with NA is just anecdotally reported in the literature. Whilst NIV does not assure a protected patent airway and requires the patient’s cooperation, it is a handy tool during surgery under NA: NIV is reported to be successful for treatment of acute respiratory failure; it may be delivered through the patient’s home ventilator, may reverse hypoventilation induced by sedatives or inadvertent spread of anaesthetic up to cervical dermatomes, and allow the avoidance of intubation in patients affected by chronic respiratory failure, prolonging the time of non-invasiveness of respiratory support (i.e., neuromuscular patients needing surgery). All these advantages could make NIV preferable to oxygen in carefully selected patients.

Background and Purpose Current guidelines do not provide firm directions on atrial fibrillation (AF) screening after ischemic stroke (IS). We sought to investigate the association of implantable cardiac monitoring (ICM) duration with the yield of AF detection in IS patients. Methods We included studies reporting AF detection rates by ICM in IS patients with negative initial AF screening. We excluded studies reporting prolonged cardiac monitoring with devices other than ICM, not providing AF detection rates or monitoring duration, and reporting overlapping data for the same population. The random-effects model was used for all pooled estimates and meta-regression analyses. Results We included 28 studies (4,531 patients, mean age 65 years). In meta-regression analyses, the proportion of AF detection by ICM was independently associated with monitoring duration (coefficient=0.015; 95% confidence interval [CI], 0.005 to 0.024) and mean patient age (coefficient=0.009; 95% CI, 0.003 to 0.015). No associations were detected with other patient characteristics, including IS subtype (cryptogenic vs. embolic stroke of undetermined source) or time from IS onset to CM implantation. In subgroup analyses, significant differences (P12 and ≤24 months: 26% [95% CI, 22% to 31%]; >24 months: 34% [95% CI, 29% to 39%]). Conclusions Extended duration of ICM monitoring and increased patient age are factors that substantially increase AF detection in IS patients with initial negative AF screening.

Con este trabajo se pretende abordar el funcionamiento de la economía occidental en el periodo comprendido entre 1950 y 1973. Con esas coordenadas espaciales y temporales en mente, se propone un esquema tripartito. En una primera parte, se procederá a una descripción de esa etapa de super-crecimiento económico que abarcó el tercer cuarto del siglo XX, prestando especial atención al desarrollo industrial y a la innovación productiva. Luego, en una segunda sección, se ensayará una explicación para esta fase de excepcional bonanza. En ese segmento del texto, se tomará distancia de un “ofertismo ciego”, explorando las condiciones que condujeron a una auténtica explosión de la demanda (reestructuración del capitalismo y primer jalón de la globalización). Finalmente, en un tercer momento, se propone una aproximación a las causas que dieron fin a los “años dorados”, modelando una narrativa en la que se hilvanan factores monetarios, demográficos, sociales y económicos. En términos metodológicos, en tanto material de cátedra, el artículo se nutre de la literatura sobre el tema, pero también de fuentes estadísticas, recursos cartográficos e imágenes de época.

Andrea Saporito,1 José Aguirre,2 Alain Borgeat,2 Andreas Perren,3 Luciano Anselmi,1 Roberto Poggi,4 Bruno Minotti,5 Stefano Cafarotti,6 Davide La Regina,7 Samuele Ceruti81Service of Anesthesiology, Ospedale Regionale di Bellinzona e Valli, Bellinzona, Switzerland; 2Department of Anesthesiology, Balgrist University Hospital, Zürich, Switzerland; 3Department of Intensive Care, Ospedale Regionale di Bellinzona e Valli, Bellinzona, Switzerland; 4Service of Anesthesiology, Ospedale Regionale di Lugano, Lugano, Switzerland; 5Department of Emergency Medicine, St Gallen General Hospital, St Gallen, Switzerland; 6Service of Thoracic Surgery, Ospedale Regionale di Bellinzona e Valli, Bellinzona, Switzerland; 7Service of Visceral Surgery, Ospedale Regionale di Bellinzona e Valli, Bellinzona, Switzerland; 8Department of Intensive Care, Geneva University Hospital (HUG), Geneva, SwitzerlandIntroduction: Breast surgery is associated with persistent postsurgical pain; usually related to poorly treated acute pain. Paravertebral block has been successfully employed in analgesic protocols for breast surgery; its impact on postdischarge pain (PDP) has not been investigated. The aim of this study was to assess characteristics of PDP after breast surgery, the development of chronic postoperative pain (CPP) and its impact on health care costs.Methods: We conducted a retrospective, observational study on a continuous cohort of adult female patients undergoing local breast cancer surgery under combined anesthesia. All patients were interviewed 6 months after hospital discharge. The survey was specifically conceived to assess incidence, features and duration of PDP. The overall cost of additional healthcare resources consumed with a specific relationship to persistent PDP was estimated.Results: A database of 244 patients was preliminarily analyzed. Of these, 188 were included in the following statistical analysis; 123 patients (65.2%) reported significant PDP, with a median intensity on NRS of 6 (IQR=2), more frequently described as burning and associated with paresthesia and/or hyperalgesia (87 patients, 46%). One hundred and six patients (56.5%) reported this pain as interfering with their normal daily activities, work and sleep. In 26.8% of cases (50 patients) symptoms lasted more than 1 month and in 28 patients (15.0%) pain became chronic. The majority of patients self-treated their pain with non-steroideal anti-inflammatory drugs, but in 50 patients (26.8%) this therapy was reported as ineffective. This additional consumption of healthcare resources led to a significant economical impact.Conclusion: PDP and CPP seem to be common complications after breast cancer surgery, even if a combined anesthesia technique with a thoracic paravertebral block is performed, leading to severe consequences on patients’ quality of life and increasing consumption of healthcare resources after discharge.Trial number: NCT03618459 (www.clinicaltrials.gov).Keywords: breast surgery, paravertebral block, regional anesthesia, postoperative pain

Prostate cancer is the fourth most common cancer worldwide with definitive diagnosis reliant on biopsy and human-graded histopathology. As with other pathologies, grading based on classical haematoxylin and eosin (H&E) staining of formalin fixed paraffin-embedded material can be prone to variation between pathologists, prompting investigation of biomolecular markers. Comprising around 50% of cellular mass, and with known metabolic variations in cancer, lipids provide a promising target for molecular pathology. Here we apply isomer-resolved lipidomics in combination with imaging mass spectrometry to interrogate tissue sections from radical prostatectomy specimens. Guided by the histopathological assessment of adjacent tissue sections, regions of interest are investigated for molecular signatures associated with lipid metabolism, especially desaturation and elongation pathways. Monitoring one of the most abundant cellular membrane lipids within these tissues, phosphatidylcholine (PC) 34:1, high positive correlation was observed between the n-9 isomer (site of unsaturation 9-carbons from the methyl terminus) and epithelial cells from potential pre-malignant lesions, while the n-7 isomer abundance was observed to correlate with immune cell infiltration and inflammation. The correlation of lipid isomer signatures with human disease states in tissue suggests a future role for isomer-resolved mass spectrometry imaging in assisting pathologists with prostate cancer diagnoses and patient stratification.

Self-efficacy is an important predictor of people’s behaviour and wellbeing. In this longitudinal study we investigated patterns of stability and change in early childhood educator self-efficacy (ESE) in child-centred educational practice and its predictors. Early childhood educators completed a questionnaire twice. Latent profile analysis yielded four profiles: decrease profile (21.2%), increase profile (25.0%), low profile (9.6%), and high profile (44.2%). Profiles were used as the outcome of a multinomial logistic regression analysis. The analyses showed that educators’ experience, number of hours worked per week, and institution are significant predictors for profile membership: educators with less professional experience and fewer working hours per week have a higher probability of being in the low profile. Family-based educators have a higher probability of being in the decrease profile than centre-based educators. The lack of opportunities to increase self-efficacy available to less experienced, part-time educators and family-based working educators are discussed in frame of Bandura’s (1997) sources of self-efficacy. Practical interventions such as coaching and tandem building are proposed to strengthen ESE.

The nature of research on speech communication in asymmetrical interactions, such as those between a speech therapist and patient, is discussed and some general approaches to therapy are noted. The situation of the aphasic is then considered, in which intervention is particularly difficult due to the lack of some important aspects of interpersonal communication. A study of three interaction situations is then reported. In the study, the language of three individuals (speech therapist, teacher, and spouse) in interaction with an aphasic was analyzed for evidence of individual differences. The results are used to illustrate the importance of individual differences in communication style in the effectiveness of the interaction. Contains 10 references. (MSE)

This paper investigates the feasibility of using a linear current sensing (LCS) technique integrated on an unmanned aerial system (UAS) for detecting and mapping underground infrastructure rapidly and cost-effectively. The LCS technique is based on data from a wide band of electromagnetic induction frequencies (50 kHz to 2 MHz) using a vector magnetic field gradiometer. This technique takes advantage of a slowly decaying secondary magnetic field in order to achieve greater standoff detection distance (1R2 vs. 1R6 for compact metallic targets during EMI sensing, where R is the distance from a target to the sensor). These secondary magnetic fields are produced by the excite current on long conductors, allowing detection at a distance of 10 meters or more. The system operates between tens of kHz to a few MHz and uses either an active EMI source or existing EM fields to excite this linear current on a long metallic subsurface target. Once excited, these linear currents produce a secondary magnetic field that is detected with an above ground triaxial magnetic field gradiometer. By moving and tracking its geolocation, the system outputs rich datasets sufficient to support high-fidelity forward and inverse EMI models for estimating the depth and orientation of deep underground long linear metallic infrastructure. The system’s hardware and its integration to a UAS system are outlined, along with the formulation of LCS theory, and numerical and experimental data are presented. The results illustrate that the LCS technique offers large standoff detection, is adaptable to UAS, and could be used effectively for detecting deep underground infrastructure such as wires and pipes.

Abstract Background Alpha-synuclein is a key protein implicated in the pathogenesis of Parkinson's disease (PD). It is the main component of the Lewy bodies, a cardinal neuropathological feature in the disease. In addition, whole locus multiplications and point mutations in the gene coding for alpha-synuclein lead to autosomal dominant monogenic PD. Over the past decade, research on PD has impelled the development of new animal models based on alpha-synuclein. In this context, transgenic mouse lines have failed to reproduce several hallmarks of PD, especially the strong and progressive dopaminergic neurodegeneration over time that occurs in the patients. In contrast, viral vector-based models in rats and non-human primates display prominent, although highly variable, nigral dopaminergic neuron loss. However, the few studies available on viral vector-mediated overexpression of alpha-synuclein in mice report a weak neurodegenerative process and no clear Lewy body-like pathology. To address this issue, we performed a comprehensive comparative study of alpha-synuclein overexpression by means of recombinant adeno-associated viral vectors serotype 2/7 (rAAV2/7) at different doses in adult mouse substantia nigra. Results We noted a significant and dose-dependent alpha-synucleinopathy over time upon nigral viral vector-mediated alpha-synuclein overexpression. We obtained a strong, progressive and dose-dependent loss of dopaminergic neurons in the substantia nigra, reaching a maximum of 82% after 8 weeks. This effect correlated with a reduction in tyrosine hydroxylase immunoreactivity in the striatum. Moreover, behavioural analysis revealed significant motor impairments from 12 weeks after injection on. In addition, we detected the presence of alpha-synuclein-positive aggregates in the remaining surviving neurons. When comparing wild-type to mutant A53T alpha-synuclein at the same vector dose, both induced a similar degree of cell death. These data were supported by a biochemical analysis that showed a net increase in soluble and insoluble alpha-synuclein expression over time to the same extent for both alpha-synuclein variants. Conclusions In conclusion, our in vivo data provide evidence that strong and significant alpha-synuclein-induced neuropathology and progressive dopaminergic neurodegeneration can be achieved in mouse brain by means of rAAV2/7.