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Original Equipment Manufacturers (OEMs) have sought new supply chain paradigms that allowed them to focus on core activities, i.e. overall product design and commercialisation. This pursuit led to partnerships with a new generation of tier-1 strategic suppliers acting as integrators. Integrators are not only responsible for system supply, but also for system design. However, critical integrators were not able to live up to their new roles, which led to costly delays in development and production. These failures highlight the ineptitude of current risk management practices employed by OEMs. To support OEMs in implementing a more differentiated and suitable approach to the use of integrators, this paper proposes a mathematical programming model for Supply Chain Design (SCD). Instead of looking at the introduction of integrators as a dichotomous decision, the model suggests the optimal number of integrators, i.e. systems, and individual part suppliers. We propose new measures for integration risk, which build upon current risk assessment practices. Robust optimisation is used to study the effect of uncertainty over baseline risk values. All approaches were tested using both randomly generated instances and real data from a large European OEM in the aerospace industry. [ABSTRACT FROM AUTHOR]

SARS-CoV-2 infection ranges from mild to severe presentations, according to the intensity of the aberrant inflammatory response. Purinergic receptors dually control the inflammatory response: while adenosine A2A receptors (A2ARs) are anti-inflammatory, ATP P2X7 receptors (P2X7Rs) exert pro-inflammatory effects. The aim of this study was to assess if there were differences in allelic and genotypic frequencies of a loss-of-function SNP of ADORA2A (rs2298383) and a gain-of-function single nucleotide polymorphism (SNP) of P2RX7 (rs208294) in the severity of SARS-CoV-2-associated infection. Fifty-five individuals were enrolled and categorized according to the severity of the infection. Endpoint genotyping was performed in blood cells to screen for both SNPs. The TT genotype (vs. CT + CC) and the T allele (vs. C allele) of P2RX7 SNP were found to be associated with more severe forms of COVID-19, whereas the association between ADORA2A SNP and the severity of infection was not significantly different. The T allele of P2RX7 SNP was more frequent in people with more than one comorbidity and with cardiovascular conditions and was associated with colorectal cancer. Our findings suggest a more prominent role of P2X7R rather than of A2AR polymorphisms in SARS-CoV-2 infection, although larger population-based studies should be performed to validate our conclusions. [ABSTRACT FROM AUTHOR]

Objective: Mutations in the genes coding for succinate dehydrogenase (SDHx) are the most frequent germline alterations in pheochromocytomas and paragangliomas. Evidence for the advantages associated with presymptomatic screening for SDHx mutation carriers is scarce. This study describes a nationwide cohort of these mutation carriers and aims to compare patients with clinical manifestations of the disease and those diagnosed through genetic screening. DESIGN: Cross‐sectional study. Patients: SDHx mutation carriers (n = 118) followed through the Portuguese Oncology referral centres: 41 probands and 77 nonprobands. Measurements: All participants were subjected to biochemical and body imaging examinations for a complete assessment of the extent and spread of disease. Clinical data obtained this way were further analysed. Results: The mean age of this cohort was 44.5 ± 17.4 years, and more than half carried the same founder SDHB mutation. About 50.8% of the mutation carriers developed pheochromocytomas or paragangliomas. Compared to patients diagnosed through genetic screening, those diagnosed clinically were characterized by larger tumours (P <.001), more frequent metastases (P =.024), were more frequently subjected to surgery (P =.011) and radiotherapy (P =.013), and had worse outcomes, such as macroscopic positive margins (P =.034). Persistent and/or unresectable disease and disease‐related mortality were also more frequent in symptomatic patients compared to those diagnosed through genetic screening (P =.014). Conclusions: In this nationwide cohort study, a large proportion of mutation carriers were found to develop SDHx‐related neoplasia. Genetic testing and subsequent follow‐up resulted in the diagnosis of smaller and nonmetastatic tumours, fewer treatment procedures, fewer complications and greater number of disease‐free patients. [ABSTRACT FROM AUTHOR]

Introduction. The diagnostic value of calcitonin (CT) measurement in fine-needle aspirate washout (FNA-CT) for medullary thyroid cancer (MTC) lymph node (LN) metastases remains to be determined. It may increase the diagnostic sensitivity, but data on this subject is sparse. Objective. Our study aimed to evaluate the utility of FNA-CT in the diagnosis of LN metastases of MTC. Methods. We retrospectively investigated, in our institutional database, 69 consecutive FNA LN cytology from 42 patients who underwent FNA cytology and CT measurement in needle washout for suspicious LN between 2012 and 2017. Results. From the total of 69 FNA, 30 (43.4%) were performed in patients with personal history of MTC. MTC was detected in 19 FNA cytology (27.5%), and CT was detectable in needle washout in 23 cases (median = 2014 pg/mL; interquartile range = 490–15111 pg/mL). Based on the combined results of FNA-CT and FNA cytology, LN surgical resection was performed in 33 cases (47.8%). Histology reported MTC LN metastases in 21 lesions (63.6%). Regarding the diagnosis of MTC LN metastases, FNA cytology showed sensitivity of 81.8% and specificity of 97.9%, and FNA-CT demonstrated sensitivity of 100% and specificity of 97.9%. We determined through ROC analysis an optimal FNA-CT cut-off value of 23 pg/mL for the diagnosis of LN metastases (sensitivity 100%; specificity 100%). Conclusions. FNA-CT may be a valuable diagnostic tool for detection of MTC LN metastases, along with FNA cytology, and it should be included in the clinical workup of neck adenopathies in patients with MTC or with thyroid nodules. [ABSTRACT FROM AUTHOR]

Somatosensory tinnitus is a generally agreed subtype of tinnitus that is associated with activation of the somatosensory, somatomotor, and visual-motor systems. A key characteristic of somatosensory tinnitus is that is modulated by physical contact or movement. Although it seems common, its pathophysiology, assessment and treatment are not well defined. We present a scoping review on the pathophysiology, diagnosis, and treatment of somatosensory tinnitus, and identify priority directions for further research. Methods: Literature searches were conducted in Google Scholar, PubMed, and EMBASE databases. Additional broad hand searches were conducted with the additional terms etiology, diagnose, treatment. Results: Most evidence on the pathophysiology of somatosensory tinnitus suggests that somatic modulations are the result of altered or cross-modal synaptic activity within the dorsal cochlear nucleus or between the auditory nervous system and other sensory subsystems of central nervous system (e.g., visual or tactile). Presentations of somatosensory tinnitus are varied and evidence for the various approaches to treatment promising but limited. Discussion and Conclusions: Despite the apparent prevalence of somatosensory tinnitus its underlying neural processes are still not well understood. Necessary involvement of multidisciplinary teams in its diagnosis and treatment has led to a large heterogeneity of approaches whereby tinnitus improvement is often only a secondary effect. Hence there are no evidence-based clinical guidelines, and patient care is empirical rather than research-evidence-based. Somatic testing should receive further attention considering the breath of evidence on the ability of patients to modulate their tinnitus through manouvers. Specific questions for further research and review are indicated. [ABSTRACT FROM AUTHOR]

Objectives: Benign paroxysmal positioning vertigo (BPPV) has significant recurrence rates, mainly in older patients. The etiopathology of recurrent BPPV is possibly related to low serum vitamin D levels. Finding a therapeutic weapon will help with these complicated cases, reducing disability, falling risk and also health care costs. Study design:Clinical trial: one-year duration. Setting: Ten patients with diagnosis of BPPV made by history and physical examination and at least two episodes of documented BPPV in the previous two years and chronic complaints of dizziness. Neurologic and other otological diseases were excluded for these patients. Subjects and methods: Vitamin D was evaluated by measuring serum 25-hydroxyvitamin D (25-OHD). Levels below 20 ng/mL were considered deficiency and levels between 20 and 30 ng/mL were considered insufficiency. Half of the patients (treatment group) started a treatment with cholecalciferol while the remaining patients were the control group. All of the patients were reevaluated every three months. Results: All patients of the treatment group did not have any subsequent episode of positional vertigo, dizziness complaints or nystagmus evoked by provocative manoeuvers. At reevaluations, the mean value of serum 25-OHD for the treatment group had increased noticeably. It was also significantly higher than the mean value of control group. All patients of control group had positional vertigo episodes, as well as positional nystagmus at office reevaluations. Conclusion: These results support the need to systematically measure and correct vitamin D levels in patients with recurrent BPPV. [ABSTRACT FROM AUTHOR]

Abstract: Prenatal cocaine exposure causes alterations in auditory brainstem response in children and experimental animals and has adverse effects on auditory information processing and language skills in children. These effects may result from lesions in the cochlea since this organ is particularly sensitive to chemical insults during the development. We have thus studied here the effect of prenatal cocaine exposure on the maturation of the rat cochlea using the transient non-catecholaminergic expression of tyrosine hydroxylase in spiral ganglion neurons as an index of cochlear maturation and morphometry to evaluate the maturation of primary auditory neurons and the organ of Corti. We showed that prenatal cocaine exposure accelerated the cochlear maturation. In the basal coil of cochleas from PND8 cocaine-treated pups, the Kölliker''s organ had disappeared, the tunnel of Corti was opened, and the stria vascularis no longer contained undifferentiated marginal cells. The maximum expression of tyrosine hydroxylase in type I primary auditory neurons occurred at PND8 instead of PND12 in pair-fed controls. On the other hand, the prenatal cocaine exposure had no effect on the width and height of the organ of Corti, spiral ganglion volume and number and size of primary auditory neurons. In conclusion, our data suggest that prenatal cocaine exposure, though not lethal to primary auditory neurons, accelerates aspects of the cochlear sensorineural maturation. This accelerated cochlear maturation in cocaine-treated rat pups could cause auditory dysfunctions by desynchronizing the development of the whole auditory pathway. [Copyright &y& Elsevier]

Nontraumatic haematoma of parapharyngeal space is very rare and may cause dysphagia and dyspnea. The authors present a case report of a 74-year-old woman with sudden nontraumatic neck swelling without dyspnea and with left pharyngeal bulging and endolaryngeal displacement. Parathyroid hormone elevation and imaging exams confirmed bleeding from a parathyroid adenoma. Symptoms and signs resolved after one week of conservative treatment. There are few cases of parapharyngeal haematomas caused by parathyroid adenomas. Most patients can be managed without emergent surgery, but close airway monitoring is fundamental. [ABSTRACT FROM AUTHOR]

Self-efficacy can be defined as the trust that individuals carry in their abilities to perform certain task or their ability to organize and carry out activities in stressful situations, being determining in behavior modification. We evaluated the self-efficacy in 58 patients with tinnitus complaints. By using the t-test for equality of averages, for general self-efficacy, self-efficacy of initiation and persistence, and self-efficacy for adversity, it has been attained that self-efficacy perceived by men is higher than amongst women. For social self-efficacy there cannot be found any statistically significant differences. Through Pearson's Correlation it has been verified that there are correlations between the values obtained in the range of general self-efficacy and its subscales and age, years of schooling, time with the complaint of tinnitus, and QoL measured by THI, not existing correlations with the values of the VAS for the intensity of tinnitus. The obtained results confirm the existence of various relations between perceived self-efficacy and QoL values of individuals with tinnitus. Being a variable that has a cognitive component combined with emotional aspects, it may be helpful to find strategies to improve self-efficacy. The use of a physical instrument like a small manual, which the patient can be able to access whenever he has doubts or feels more upset about the tinnitus, and that may give him information about their problem, as well as strategies to improve how to deal with it more efficiently, can be an asset for these patients. [ABSTRACT FROM AUTHOR]