Introduction L’association des tumeurs multiples a été décrite dans la littérature, en dehors des causes syndromiques. Observation Nous rapportons le cas d’un homme de 64 ans, évaluée en 2015, avec ...antécédents de : maladie de Still (corticothérapie pendant 12 ans), syndrome coronarien aigu (2015–4 stents actifs), double prothèse de la hanche, stents iliaques bilatérales (2009), diabète de type 2, tabac 20PA. Dans les antécédents familiaux, on remarque : leucémie chez sa mère décédée à l’âge de 52 ans, leucémie et thyroïdectomie (goitre multinodulaire) chez sa sœur (68 ans). Un scanner TAP effectué pour des douleurs lombaires retrouvait : nodule rénal droit de 22 mm, deux nodules prostatiques, neurinome L1-L2, multiples angiomes hépatiques, un adénome surrénalien gauche (le bilan réalisée ne montre pas d’hyper sécrétion hormonale). L’échographie e ffectuée suite à un examen cervical pathologique, montrait : nodule droit (24 × 28 × 44 mm) TIRAD 4A et nodule gauche (19 × 24 × 31 mm) TIRADS 4B, sans adénomégalie cervicale. Le patient est en hyperthyroïdie, la scintigraphie thyroïdienne montrant un nodule chaud droit. Tous ces nodules sont stables en dimensions 6 mois après leur découverte. La biopsie des nodules a été temporisée (patient sous double anti-agrégation KARDEGIC/EFIENT, qu’on arrêtera temporairement en juin 2016, selon l’avis cardiologique). Un PET-FDG a été programmé en attente. Discussion La littérature médicale décrit quelques cas de tumeurs primitifs synchrones ; il n’y a pas d’article sur les nodules multiples non cancéreux. Il n’y a pas de cause génétique signalé, mais les antécédents de leucémie pourraient nous faire pousser les explorations, en fonction des résultats du PET-FDG et des biopsies.
Introduction La pancréatite aiguë n’est pas une complication classique du syndrome de Cushing. Observation Nous rapport le cas d’une femme de 45 ans, évaluée en 2014 dans le Service d’Endocrinologie ...du CHU Iasi, avec antécédents de diabète de type 2 et HTA, sans notion d’intoxication etanolique ou litiase vésiculaire. L’examen clinique a retrouvé les signes d’hypercortisolism (hypotrophie musculaire des membres inférieures, vergetures pourpres d’apparition récente, echimoses multiples), l’obésité morbide avec distribution androïde, TA 160/90 mmHg. Le bilan hormonal fait le diagnostic positif d’hypercortisolism et identifie son caractère ACTH dépendant : cortisol matinal 39ug/dl (N : 5- 25), ACTH 97 pg/ml (N 0-46), cortisol matinal après DXM 1 mg 16ug/dl (N < 1,8 ug/dl), cortisol matinal après DXM 2mgx2 : 2,1ug/dl. Cette inhibition de l’axe corticotrope est plutôt en faveur de la Maladie de Cushing. Le 30/04/2014, pendant l’hospitalisation dans notre service, la patiente a présenté une douleur épigastrique d’apparition brutale. Le bilan biochimique (lipasemie, amilazurie) était en faveur d’une pancréatite aiguë. L’échographie abdominale n’a pas révélé les calculs biliaires peuvent expliquer la survenue de la pancréatite. La patiente a été transférée dans le Service de Gastro-Entérologie. Discussion Jusqu’à présent, la littérature médicale décrit quelques dizaines de cas d’hypercortisolisme exogène associés à une pancréatite aiguë. L’association de celle-ci au Syndrome de Cushing est beaucoup moins fréquente. Ce cas clinique ne peut pas établir une relation cause-effet hypercortisolisme endogène-pancréatite aiguë, mais soulève la souspicion d’un rôle favorisant ou déclanchateur.
Anodic oxidation of niobium has been investigated in an electrolyte solution containing calcium phosphate and calcium acetate. The oxide layer morphology has been determined by combining 3D Atomic ...Force Microscopy images and cross-sectional Field Emission SEM measurements. The surface sensitivity of high-resolution X-ray Photoemission Spectroscopy has been exploited to evaluate the chemical composition of the outermost oxide surface, a key feature in view of implant development. Anodic Spark Deposition (ASD) results in the formation of micrometer-thick oxide layers showing a porous morphology suitable for osseointegration purposes. Increasing the maximum potential attained during oxidation leads to an increase of the oxide thickness and pore size accompanied by a noticeable surface enrichment with calcium and phosphorus. Remarkably, a maximal Ca/P ratio of 1.8 was achieved for anodization at 250 V, promising for osseointegration thanks to the similarity with hydroxyapatite stoichiometry. Parallel experiments performed on titanium under the same conditions indicated a maximal Ca/P ratio of 1.3 and pores of smaller dimensions. The comparative analysis suggests that niobium may represent a promising alternative to titanium to be explored for implant development.
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•3D AFM mapping of porous oxide layers•High-resolution XPS analysis of the outermost oxide surfaces•Pore size, layer thickness, Ca and P inclusions tunable by anodizing potential•Maximal Ca/P ratio of ~1.8 at anodizing potential of 250 V
Abstract
We report on the results of an extensive campaign of optical and mechanical characterization of the ion-beam sputtered oxide layers (Ta
2
O
5
, TiO
2
, Ta
2
O
5
–TiO
2
, SiO
2
) within the ...high-reflection coatings of the Advanced LIGO, Advanced Virgo and KAGRA gravitational-wave detectors: refractive index, thickness, optical absorption, composition, density, internal friction and elastic constants have been measured; the impact of deposition rate and post-deposition annealing on coating internal friction has been assessed. For Ta
2
O
5
and SiO
2
layers, coating internal friction increases with the deposition rate, whereas the annealing treatment either erases or largely reduces the gap between samples with different deposition history. For Ta
2
O
5
–TiO
2
layers, the reduction of internal friction due to TiO
2
doping becomes effective only if coupled with annealing. All measured samples showed a weak dependence of internal friction on frequency
ϕ
c
(
f
) =
af
b
, with −0.208 <
b
< 0.140 depending on the coating material considered. SiO
2
films showed a mode-dependent loss branching, likely due to spurious losses at the coated edge of the samples. The reference loss values of the Advanced LIGO and Advanced Virgo input (ITM) and end (ETM) mirror HR coatings have been updated by using our estimated value of Young’s modulus of Ta
2
O
5
–TiO
2
layers (120 GPa) and are about 10% higher than previous estimations.
Introduction La pseudohypoparathyroïdie est une maladie génétique héréditaire rare subdivisée en plusieurs entités distinctes caractérisées par résistance à l’action de la parathormone, accompagnée ...par des malformations squelettiques et de développement distinctes. Observations Nous rapportons le cas d’un garçon de 8 ans, évalué en juin 2013, avec antécédents d’hypospadias, cryptorchidie, plusieurs épisodes de convulsions considérées d’origine épileptique. Un retard dans le développement du langage avait conduit au diagnostic d’autisme. L’examen clinique a révélé une taille petite (–1,7 DS), obésité (+4,4 DS), dimorphisme avec le visage arrondi, cou court, pyramide nasale aplatie, développement des dents retardé, brachymétacarpie bilatérale du cinquième doigt, suggestif pour Ostéodystrophie Héréditaire Albright. Le bilan biologique plaidait pour une résistance à la PTH avec hypocalcémie (Ca T = 5,84 mg/dL, Ca ionisé = 0,7 mmol/L), hyperphosphatémie (phosphore = 11,6 mg/dL), PTH élevée (414 pg/mL), associée avec d’autres probables résistances (TSH, GnRH). Un scanner cérébral antérieur montrait des calcifications du noyau lenticulaire. Discussions Ce cas clinique met en évidence la difficulté d’un diagnostic précoce correct de la pseudohypoparathyroïdie. Il est possible que le retard mental et le retard du développement du langage soient dus à la maladie, les convulsions représentant probablement une première manifestation de l’hypocalcémie. Un examen clinique détaillé aurait pu observer l’aspect phénotypique spécifique et avec un bilan biologique adéquate, aurait pu établir précocement le diagnostic. Une prise en charge précoce de l’hypocalcémie aurait pu éviter les conséquences majeures sur l’évolution de l’enfant..
Non–small-cell lung cancers (NSCLCs) containing EGFR mutations are exquisitely sensitive to epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs). This is the case of the most ...common EGFR mutations affecting exon 18 (G719X), 19 (inframe deletions), and 21 (L858R and L861Q). However, the frequency of compound (i.e., double or complex) EGFR mutations—where an EGFR TKI sensitizing or other mutation is identified together with a mutation of unknown clinical significance—and their pattern of response/resistance to EGFR TKIs are less well described.
We analyzed the EGFR mutation pattern of 79 cases of NSCLC harboring EGFR mutations and compiled the genotype-response data for patients with NSCLCs with compound EGFR mutations treated with EGFR TKIs.
Of the 79 EGFR-mutated tumors identified, 11 (14%) had compound mutations. Most involved the EGFR TKI–sensitizing G719X (n = 3, plus S768I or E709A), L858R (n = 4, plus L747V, R776H, T790M, or A871G), L861Q (n = 1, plus E709V), and delL747_T751 (n = 1, plus R776H). Eight patients received an EGFR TKI: three cases with G719X plus another mutation had partial responses (PRs) to erlotinib; of three cases with L858R plus another mutation, two displayed PRs and one (with EGFR-L858R+A871G) progressive disease (PD) to erlotinib; one NSCLC with EGFR-L861Q+E709A and one with delL747_T751+R776S had PRs to EGFR TKIs.
Compound EGFR mutations comprised 14% of all mutations identified during routine sequencing of exons 18–21 of EGFR in our cohort. Most patients with an EGFR TKI–sensitizing mutation (G719X, exon 19 deletion, L858R, and L861Q) in addition to an atypical mutation responded to EGFR TKIs. Reporting of the genotype-response pattern of NSCLCs with EGFR compound and other rare mutations, and the addition of this information to searchable databases, will be helpful to select the appropriate therapy for EGFR-mutated NSCLC.
Objective: The bidirectional communication between the user and the prosthesis is an important requirement when developing prosthetic hands. Proprioceptive feedback is fundamental to perceiving ...prosthesis movement without the need for constant visual attention. We propose a novel solution to encode wrist rotation using a vibromotor array and Gaussian interpolation of vibration intensity. The approach generates tactile sensation that smoothly rotates around the forearm congruently with prosthetic wrist rotation. The performance of this scheme was systematically assessed for a range of parameter values (number of motors and Gaussian standard deviation). Methods: Fifteen able-bodied subjects and one individual with congenital limb deficiency used vibrational feedback to control the virtual hand in the target-achievement test. Performance was assessed by end-point error and efficiency as well as subjective impressions. Results: The results showed a preference for smooth feedback and a higher number of motors (8 and 6 versus 4). With 8 and 6 motors, the standard deviation, determining the sensation spread and continuity, could be modulated through a broad range of values (0.1 - 2) without a significant performance loss (error: ∼ 10%; efficiency: ∼ 30%). For low values of standard deviation (0.1-0.5), the number of motors could be reduced to 4 without a significant performance decrease. Conclusion: The study demonstrated that the developed strategy provided meaningful rotation feedback. Moreover, the Gaussian standard deviation can be used as an independent parameter to encode an additional feedback variable. Significance: The proposed method is a flexible and effective approach to providing proprioceptive feedback while adjusting the trade-off between sensation quality and the number of vibromotors.
Hereditary transthyretin amyloidosis (ATTRv, v for variant) is a late-onset, autosomal dominant disease caused by progressive extracellular deposition of transthyretin amyloid fibrils, leading to ...organ damage and death. For other late-onset fatal diseases, as Huntington's disease, protocols for pre-symptomatic genetic testing (PST) are available since decades. For ATTRv, limited experience has been reported to date, mostly gathered before the availability of approved therapies. We aimed at developing recommendations for a safe and feasible PST protocol in ATTRv in the era of emerging treatments, taking also into account Italian patients' characteristics and healthcare system rules. After an initial survey on ongoing approaches to PST for ATTRv in Italy, two roundtable meetings were attended by 24 experts from 16 Italian centers involved in the diagnosis and care of this disease. Minimal requirements for PST offer and potential critical issues were highlighted. By November 2019, 457 families affected by ATTRv with 209 molecularly confirmed pre-symptomatic carriers were counted. The median age at PST was 41.3 years of age, regardless of the specific mutation. Half of the Italian centers had a multidisciplinary team, including a neurologist, an internist, a cardiologist, a medical geneticist and a psychologist, although in most cases not all the specialists were available in the same center. A variable number of visits was performed at each site. Experts agreed that PST should be offered only in the context of genetic counselling to at risk individuals aged 18 or older. Advertised commercial options for DNA testing should be avoided. The protocol should consist of several steps, including a preliminary clinical examination, a pre-test information session, an interval time, the genetic test and a post-test session with the disclosure of the test results, in the context of an experienced multidisciplinary team. Recommendations for best timing were also defined. Protocols for PST in the context of ATTRv can be refined to offer at risk individuals the best chance for early diagnosis and timely treatment start, while respecting autonomous decisions and promoting safe psychological adjustment to the genetic result.
Our current approaches to resource management are not sustainable. Businesses typically follow a linear approach where resources are not well utilized. Maritime ports are part of the problem, as they ...need to optimize the use of resources and generate negative externalities. However, they can also be important drivers of sustainability if they effectively transition to Circular Economy (CE). In this study, eight principles of CE and ten CBMs, are discussed and used to analyze ports in three areas of intervention. This paper analyzes current CE practices in European ports and the potential to adopt Circular Business Models (CBMs) to create value for port stakeholders and contribute to the United Nations Sustainable Development Goals (SDGs). Drivers and barriers to CE were analyzed, and the level of development was assessed. The ports studied are in Europe and are generally regarded as Maritime Industrial Ports (MIP). The methodology includes a Semi-Systematic Literature Review (SSLR) and a SWOT analysis to examine CE practices in maritime ports. This methodology helped enhance the analysis of Drivers and Barriers to CE transition. This study concludes that ports are developing circular practices and business models on the technical and biological flows, but the level of implementation is moderated to low. Six drivers for adopting CE principles were identified, including European ports' experience in circular activities and the Quality & Environmental Management System (EMS). In addition, seven barriers to CE were highlighted, including the diversity of port characteristics and the different interests and ambitions of port stakeholders that make it difficult to standardize measurements and transition to circularity. Circular development goals in ports should be integrated, and development must balance social, economic, and environmental sustainability. The findings and implications of this study will help Port Authorities (PA) in the strategy, policy development, and implementation of CBMs.
Replacing the human hand with artificial devices of equal capability and effectiveness is a long-standing challenge. Even the most advanced hand prostheses, which have several active degrees of ...freedom controlled by the electrical signals of the stump's residual muscles, do not achieve the complexity, dexterity, and adaptability of the human hand. Thus, prosthesis abandonment rate remains high due to poor embodiment. Here, we report a prosthetic hand called Hannes that incorporates key biomimetic properties that make this prosthesis uniquely similar to a human hand. By means of an holistic design approach and through extensive codevelopment work involving researchers, patients, orthopaedists, and industrial designers, our proposed device simultaneously achieves accurate anthropomorphism, biomimetic performance, and human-like grasping behavior that outperform what is required in the execution of activities of daily living (ADLs). To evaluate the effectiveness and usability of Hannes, pilot trials on amputees were performed. Tests and questionnaires were used before and after a period of about 2 weeks, in which amputees could autonomously use Hannes domestically to perform ADLs. Last, experiments were conducted to validate Hannes's high performance and the human likeness of its grasping behavior. Although Hannes's speed is still lower than that achieved by the human hand, our experiments showed improved performance compared with existing research or commercial devices.
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