ResearchPad - 8 https://www.researchpad.co Default RSS Feed en-us © 2020 Newgen KnowledgeWorks <![CDATA[Linking Motoneuron PIC Location to Motor Function in Closed-Loop Motor Unit System Including Afferent Feedback: A Computational Investigation]]> https://www.researchpad.co/article/elastic_article_8062 The goal of this study is to investigate how the activation location of persistent inward current (PIC) over motoneuron dendrites is linked to motor output in the closed-loop motor unit. Here, a physiologically realistic model of a motor unit including afferent inputs from muscle spindles was comprehensively analyzed under intracellular stimulation at the soma and synaptic inputs over the dendrites during isometric contractions over a full physiological range of muscle lengths. The motor output of the motor unit model was operationally assessed by evaluating the rate of force development, the degree of force potentiation and the capability of self-sustaining force production. Simulations of the model motor unit demonstrated a tendency for a faster rate of force development, a greater degree of force potentiation, and greater capacity for self-sustaining force production under both somatic and dendritic stimulation of the motoneuron as the PIC channels were positioned farther from the soma along the path of motoneuron dendrites. Interestingly, these effects of PIC activation location on force generation significantly differed among different states of muscle length. The rate of force development and the degree of force potentiation were systematically modulated by the variation of PIC channel location for shorter-than-optimal muscles but not for optimal and longer-than-optimal muscles. Similarly, the warm-up behavior of the motor unit depended on the interplay between PIC channel location and muscle length variation. These results suggest that the location of PIC activation over motoneuron dendrites may be distinctively reflected in the motor performance during shortening muscle contractions.

]]>
<![CDATA[Microfluidic automated plasmid library enrichment for biosynthetic gene cluster discovery]]> https://www.researchpad.co/article/N77bfd511-0a9f-457b-9ccb-92d6875a2225 Microbial biosynthetic gene clusters are a valuable source of bioactive molecules. However, because they typically represent a small fraction of genomic material in most metagenomic samples, it remains challenging to deeply sequence them. We present an approach to isolate and sequence gene clusters in metagenomic samples using microfluidic automated plasmid library enrichment. Our approach provides deep coverage of the target gene cluster, facilitating reassembly. We demonstrate the approach by isolating and sequencing type I polyketide synthase gene clusters from an Antarctic soil metagenome. Our method promotes the discovery of functional-related genes and biosynthetic pathways.

]]>
<![CDATA[Single-Pulse TMS over the Parietal Cortex Does Not Impair Sensorimotor Perturbation-Induced Changes in Motor Commands]]> https://www.researchpad.co/article/Nddedcc16-ead8-4853-9aa6-c2c8f0c52134

Abstract

Intermittent exposure to a sensorimotor perturbation, such as a visuomotor rotation, is known to cause a directional bias on the subsequent movement that opposes the previously experienced perturbation. To date, it is unclear whether the parietal cortex is causally involved in this postperturbation movement bias. In a recent electroencephalogram study, Savoie et al. (2018) observed increased parietal activity in response to an intermittent visuomotor perturbation, raising the possibility that the parietal cortex could subserve this change in motor behavior. The goal of the present study was to causally test this hypothesis. Human participants (N = 28) reached toward one of two visual targets located on either side of a fixation point, while being pseudorandomly submitted to a visuomotor rotation. On half of all rotation trials, single-pulse transcranial magnetic stimulation (TMS) was applied over the right (N = 14) or left (N = 14) parietal cortex 150 ms after visual feedback provision. To determine whether TMS influenced the postperturbation bias, reach direction was compared on trials that followed rotation with (RS + 1) and without (R + 1) TMS. It was hypothesized that interfering with parietal activity would reduce the movement bias following rotated trials. Results revealed a significant and robust postrotation directional bias compared with both rotation and null rotation trials. Contrary to our hypothesis, however, neither left nor right parietal stimulation significantly impacted the postrotation bias. These data suggest that the parietal areas targeted here may not be critical for perturbation-induced motor output changes to emerge.

]]>
<![CDATA[Aging But Not Age-Related Hearing Loss Dominates the Decrease of Parvalbumin Immunoreactivity in the Primary Auditory Cortex of Mice]]> https://www.researchpad.co/article/N025967a7-fa74-44ba-a9c0-fbe5dd9d3ed0 <![CDATA[Paired Associative Stimulation Fails to Induce Plasticity in Freely Behaving Intact Rats]]> https://www.researchpad.co/article/Nd59c3908-3060-45f8-a4a4-8f3b78060647

Abstract

Paired associative stimulation (PAS) has been explored in humans as a noninvasive tool to drive plasticity and promote recovery after neurologic insult. A more thorough understanding of PAS-induced plasticity is needed to fully harness it as a clinical tool. Here, we tested the efficacy of PAS with multiple interstimulus intervals in an awake rat model to study the principles of associative plasticity. Using chronically implanted electrodes in motor cortex and forelimb, we explored PAS parameters to effectively drive plasticity. We assessed changes in corticomotor excitability using a closed-loop, EMG-controlled cortical stimulation paradigm. We tested 11 PAS intervals, chosen to force the coincidence of neuronal activity in the motor cortex and spinal cord of rats with timings relevant to the principles of Hebbian spike timing-dependent plasticity. However, despite a relatively large number of stimulus pairings (300), none of the tested intervals reliably changed corticospinal excitability relative to control conditions. Our results question PAS effectiveness under these conditions.

]]>
<![CDATA[An Unexpected Dependence of Cortical Depth in Shaping Neural Responsiveness and Selectivity in Mouse Visual Cortex]]> https://www.researchpad.co/article/N267cf9ce-5fe0-4735-a374-0629094d3f1d

Abstract

Two-photon imaging studies in mouse primary visual cortex (V1) consistently report that around half of the neurons respond to oriented grating stimuli. However, in cats and primates, nearly all neurons respond to such stimuli. Here we show that mouse V1 responsiveness and selectivity strongly depends on neuronal depth. Moving from superficial layer 2 down to layer 4, the percentage of visually responsive neurons nearly doubled, ultimately reaching levels similar to what is seen in other species. Over this span, the amplitude of neuronal responses also doubled. Moreover, stimulus selectivity was also modulated, not only with depth but also with response amplitude. Specifically, we found that orientation and direction selectivity were greater in stronger responding neurons, but orientation selectivity decreased with depth whereas direction selectivity increased. Importantly, these depth-dependent trends were found not just between layer 2/3 and layer 4 but at different depths within layer 2/3 itself. Thus, neuronal depth is an important factor to consider when pooling neurons for population analyses. Furthermore, the inability to drive the majority of cells in superficial layer 2/3 of mouse V1 with grating stimuli indicates that there may be fundamental differences in the micro-circuitry and role of V1 between rodents and other mammals.

]]>
<![CDATA[The Operant Plantar Thermal Assay: A Novel Device for Assessing Thermal Pain Tolerance in Mice]]> https://www.researchpad.co/article/N52646525-83a8-405f-8ab1-b4c7def14b2f

Abstract

Pain is a multidimensional experience of sensory-discriminative, cognitive, and affective processes; however, current basic research methods rely heavily on response to threshold stimuli, bypassing the supraspinal processing that ultimately gives rise to the pain experience. We developed the operant plantar thermal assay (OPTA), which utilizes a novel, conflict-based operant task requiring evaluation and active decision-making to obtain reward under thermally aversive conditions to quantify thermal pain tolerance. In baseline measures, male and female mice exhibited similar temperature preferences, however in the OPTA, female mice exhibited greater temperature-dependent tolerance, as defined by choice time spent in an adverse thermal condition to obtain reward. Increasing reward salience (4% vs 10% sucrose solution) led to increased thermal tolerance for males but not females. To determine whether neuropathic and inflammatory pain models alter thermal tolerance, animals with chronic constriction injury (CCI) or complete Freund’s adjuvant (CFA), respectively, were tested in the OPTA. Surprisingly, neuropathic animals exhibited increased thermal tolerance, as shown by greater time spent in the reward zone in an adverse thermal condition, compared with sham animals. There was no effect of inflammation on thermal tolerance. Administration of clonidine in the CCI model led to increased thermal tolerance in both injured and sham animals. In contrast, the non-steroidal anti-inflammatory meloxicam was anti-hyperalgesic in the CFA model, but reduced thermal pain tolerance. These data support the feasibility of using the OPTA to assess thermal pain tolerance to gain new insights into complex pain behaviors and to investigate novel aspects of analgesic efficacy.

]]>
<![CDATA[Cerebral Contribution to the Execution, But Not Recalibration, of Motor Commands in a Novel Walking Environment]]> https://www.researchpad.co/article/N939577c6-9a69-47b0-8b76-b37814c63e4e

Abstract

Human movements are flexible as they continuously adapt to changes in the environment. The recalibration of corrective responses to sustained perturbations (e.g., constant force) altering one’s movement contributes to this flexibility. We asked whether the recalibration of corrective actions involve cerebral structures using stroke as a disease model. We characterized changes in muscle activity in stroke survivors and control subjects before, during, and after walking on a split-belt treadmill moving the legs at different speeds. The recalibration of corrective muscle activity was comparable between stroke survivors and control subjects, which was unexpected given the known deficits in feedback responses poststroke. Also, the intact recalibration in stroke survivors contrasted their limited ability to adjust their muscle activity during steady-state split-belt walking. Our results suggest that the recalibration and execution of motor commands are partially dissociable: cerebral lesions interfere with the execution, but not the recalibration, of motor commands on novel movement demands.

]]>
<![CDATA[West Nile virus-associated vasculitis and intracranial hemorrhage]]> https://www.researchpad.co/article/N6dffed8d-72b9-4602-b49b-afd05388e805 ]]> <![CDATA[A Very Fast Time Scale of Human Motor Adaptation: Within Movement Adjustments of Internal Representations during Reaching]]> https://www.researchpad.co/article/N919cc048-0fd7-4694-87d7-2fb1ec52fb65

Humans and other animals adapt motor commands to predictable disturbances within tens of trials in laboratory conditions. A central question is how does the nervous system adapt to disturbances in natural conditions when exactly the same movements cannot be practiced several times. Because motor commands and sensory feedback together carry continuous information about limb dynamics, we hypothesized that the nervous system could adapt to unexpected disturbances online.

]]>
<![CDATA[Function, Innervation, and Neurotransmitter Signaling in Mice Lacking Type-II Taste Cells]]> https://www.researchpad.co/article/Nc4cfc42f-4a10-4b6b-a17c-a3dab0c5326d

Abstract

The Skn-1a transcription factor (Pou2f3) is required for Type II taste cell differentiation in taste buds. Taste buds in Skn-1a-/- mice lack Type II taste cells but have a concomitant expansion of Type III cells, providing an ideal model to determine the relative role of taste cell types in response specificity. We confirmed that chorda tympani responses to sweet, bitter, and umami stimuli were greatly reduced in the knock-outs (KOs) compared with wild-type (WT) littermates. Skn-1a-/- mice also had reductions to NaCl that were partially amiloride-insensitive, suggesting that both Type II and Type III cells contribute to amiloride-insensitive salt detection in anterior tongue. We also confirmed that responses to sour stimuli are equivalent in the KOs, despite the large increase in the number of Type III taste cells. To examine their innervation, we crossed the Htr3a-GFP (5-HT3A-GFP) reporter mouse with the Skn-1a-/- mice and examined geniculate ganglion neurons for GFP expression and responses to 5-HT. We found no change in the number of 5-HT3A-expressing neurons with KO of Skn-1a. Calcium imaging showed that only 5-HT3A-expressing neurons respond to exogenous 5-HT, while most neurons respond to ATP, similar to WT mice. Interestingly, despite loss of all Type II cells, the P2X3 antagonist AF353 blocked all chorda tympani responses. These data collectively raise questions pertaining the source of ATP signaling in the absence of Type II taste cells and whether the additional Type III cells are innervated by fibers that would have normally innervated Type II cells.

]]>
<![CDATA[A Comparison between Mouse, In Silico, and Robot Odor Plume Navigation Reveals Advantages of Mouse Odor Tracking]]> https://www.researchpad.co/article/N9644a4e2-0487-4ca0-9d2e-2fd363069795

Localization of odors is essential to animal survival, and thus animals are adept at odor navigation. In natural conditions animals encounter odor sources in which odor is carried by air flow varying in complexity. We sought to identify potential minimalist strategies that can effectively be used for odor-based navigation and asses their performance in an increasingly chaotic environment.

]]>
<![CDATA[Maternal Fluoxetine Exposure Alters Cortical Hemodynamic and Calcium Response of Offspring to Somatosensory Stimuli]]> https://www.researchpad.co/article/Nd207bfc7-3c89-4609-9cc9-52b3f145e7b1

Epidemiological studies have found an increased incidence of neurodevelopmental disorders in populations prenatally exposed to selective serotonin reuptake inhibitors (SSRIs). Optical imaging provides a minimally invasive way to determine if perinatal SSRI exposure has long-term effects on cortical function. Herein we probed the functional neuroimaging effects of perinatal SSRI exposure in a fluoxetine (FLX)-exposed mouse model.

]]>
<![CDATA[Eye Movements during Visuomotor Adaptation Represent Only Part of the Explicit Learning]]> https://www.researchpad.co/article/N78fd0e29-3611-4a2c-aacb-1004273fcf9e

Abstract

Visuomotor rotations are learned through a combination of explicit strategy and implicit recalibration. However, measuring the relative contribution of each remains a challenge and the possibility of multiple explicit and implicit components complicates the issue. Recent interest has focused on the possibility that eye movements reflects explicit strategy. Here we compared eye movements during adaptation to two accepted measures of explicit learning: verbal report and the exclusion test. We found that while reporting, all subjects showed a match among all three measures. However, when subjects did not report their intention, the eye movements of some subjects suggested less explicit adaptation than what was measured in an exclusion test. Interestingly, subjects whose eye movements did match their exclusion could be clustered into the following two subgroups: fully implicit learners showing no evidence of explicit adaptation and explicit learners with little implicit adaptation. Subjects showing a mix of both explicit and implicit adaptation were also those where eye movements showed less explicit adaptation than did exclusion. Thus, our results support the idea of multiple components of explicit learning as only part of the explicit learning is reflected in the eye movements. Individual subjects may use explicit components that are reflected in the eyes or those that are not or some mixture of the two. Analysis of reaction times suggests that the explicit components reflected in the eye movements involve longer reaction times. This component, according to recent literature, may be related to mental rotation.

]]>
<![CDATA[Dose–response characteristics of noninvasive ventilation in acute respiratory failure]]> https://www.researchpad.co/article/N243c0d7e-9ae3-417b-94e1-b798949ab3c1

Acute noninvasive ventilation (NIV) is a well-established therapy for acute respiratory failure but the dose–response characteristics of this therapy have not been defined. The aim of this study was to define this dose–response relationship.

This study was a retrospective review of patients receiving NIV for acute respiratory failure in a tertiary hospital respiratory high-dependency unit between July 2012 and June 2017. Mask-on time (rather than the period that NIV was in use) as the “dose” was compared with hospital survival as the “response”.

654 patients were included, 594 (91%) with hypercapnic respiratory failure (HCRF). NIV was used for a median (interquartile range (IQR)) duration of 2.74 (1.51–4.73) days and median (IQR) mask-on time was 34 (18–60) h (56.1% (41.2–69.5%) of treatment time). There was evidence of a dose–response relationship in the HCRF group up to a ceiling of 24 h mask-on time, but not in the hypoxaemic respiratory failure (HRF) group. There was a difference in survival with as little as 2 h mask-on time (92% compared with 73%; p<0.001). Patients requiring NIV for 80–100% of therapy time had lower survival.

We conclude that there is evidence of a dose–response relationship between cumulative NIV usage (mask-on time) and survival from as little as 2 h to a ceiling of ∼24 h in HCRF, but not in HRF.

]]>
<![CDATA[Evaluating the Burstlet Theory of Inspiratory Rhythm and Pattern Generation]]> https://www.researchpad.co/article/N293c9188-38c6-40b9-9809-266fe7ff0443

Abstract

The preBötzinger complex (preBötC) generates the rhythm and rudimentary motor pattern for inspiratory breathing movements. Here, we test “burstlet” theory (Kam et al., 2013a), which posits that low amplitude burstlets, subthreshold from the standpoint of inspiratory bursts, reflect the fundamental oscillator of the preBötC. In turn, a discrete suprathreshold process transforms burstlets into full amplitude inspiratory bursts that drive motor output, measurable via hypoglossal nerve (XII) discharge in vitro. We recap observations by Kam and Feldman in neonatal mouse slice preparations: field recordings from preBötC demonstrate bursts and concurrent XII motor output intermingled with lower amplitude burstlets that do not produce XII motor output. Manipulations of excitability affect the relative prevalence of bursts and burstlets and modulate their frequency. Whole-cell and photonic recordings of preBötC neurons suggest that burstlets involve inconstant subsets of rhythmogenic interneurons. We conclude that discrete rhythm- and pattern-generating mechanisms coexist in the preBötC and that burstlets reflect its fundamental rhythmogenic nature.

]]>
<![CDATA[Predicted Position Error Triggers Catch-Up Saccades during Sustained Smooth Pursuit]]> https://www.researchpad.co/article/Na74d072e-f514-495a-a9e5-1e2152bd77e3

Abstract

For humans, visual tracking of moving stimuli often triggers catch-up saccades during smooth pursuit. The switch between these continuous and discrete eye movements is a trade-off between tolerating sustained position error (PE) when no saccade is triggered or a transient loss of vision during the saccade due to saccadic suppression. de Brouwer et al. (2002b) demonstrated that catch-up saccades were less likely to occur when the target re-crosses the fovea within 40–180 ms. To date, there is no mechanistic explanation for how the trigger decision is made by the brain. Recently, we proposed a stochastic decision model for saccade triggering during visual tracking (Coutinho et al., 2018) that relies on a probabilistic estimate of predicted PE (PEpred). Informed by model predictions, we hypothesized that saccade trigger time length and variability will increase when pre-saccadic predicted errors are small or visual uncertainty is high (e.g., for blurred targets). Data collected from human participants performing a double step-ramp task showed that large pre-saccadic PEpred (>10°) produced short saccade trigger times regardless of the level of uncertainty while saccade trigger times preceded by small PEpred (<10°) significantly increased in length and variability, and more so for blurred targets. Our model also predicted increased signal-dependent noise (SDN) as retinal slip (RS) increases; in our data, this resulted in longer saccade trigger times and more smooth trials without saccades. In summary, our data supports our hypothesized predicted error-based decision process for coordinating saccades during smooth pursuit.

]]>
<![CDATA[Atti del 52° Congresso Nazionale]]> https://www.researchpad.co/article/N40742df4-0c85-42be-960e-c80df7e02214

Nel promuovere e gestire i cambiamenti necessari per coniugare pratiche sicure ed efficaci con l’efficienza, l’equità e la sostenibilità dei servizi sanitari, essenziale è la conoscenza, la diffusione e l’adesione alle raccomandazioni per la pratica professionale derivanti da linee guida (LG). In Italia la Legge 24/2017 (“Disposizioni in materia di sicurezza delle cure e della persona assistita, nonché in materia di responsabilità professionale degli esercenti le professioni sanitarie”), stabilendo che “gli esercenti le professioni sanitarie, nell’esecuzione delle prestazioni sanitarie con finalità preventive, diagnostiche, terapeutiche, palliative, riabilitative e di medicina legale, si attengono, salve le specificità del caso concreto, alle raccomandazioni previste dalle linee guida pubblicate ed elaborate da enti e istituzioni pubblici e privati nonché dalle società scientifiche e dalle associazioni tecnico-scientifiche delle professioni sanitarie iscritte in apposito elenco”, ha rinnovato l’impulso legislativo, culturale, professionale e scientifico alla diffusione delle LG nel Servizio Sanitario Nazionale. L’attuale quadro regolamentare italiano prevede che la loro produzione venga garantita sulla base degli standard di predisposizione e valutazione della qualità metodologica definiti dal Centro Nazionale per l’Eccellenza Clinica (CNEC) dell’Istituto Superiore di Sanità, punto di riferimento per l’attuazione del nuovo Sistema Nazionale Linee Guida (istituito con il DM 27 febbraio 2018) (https://snlg.iss.it).

Secondo la vigente definizione adottata dal CNEC, le LG sono uno “strumento di supporto decisionale finalizzato a consentire che, fra opzioni alternative, sia adottata quella che offre un migliore bilancio fra benefici ed effetti indesiderati, tenendo conto della esplicita e sistematica valutazione delle prove disponibili, commisurandola alle circostanze peculiari del caso concreto e condividendola-laddove possibile-con il paziente o i caregiver”. Le linee guida servono dunque a supportare i processi decisionali che connotano la pratica professionale preventiva, diagnostica, terapeutica e assistenziale, ma anche le scelte manageriali e le politiche sanitarie. Ai diversi livelli del sistema sanitario, infatti, la disponibilità di LG è fondamentale per contrastare alcune delle criticità sistemiche della sanità connesse, tra l’altro, all’erogazione di cure di qualità sub-ottimale, alla variazione ingiustificata di pratiche ed esiti e alle diseguaglianze, in un quadro di risorse limitate.

Se dunque oggi il valore delle linee guida per la pratica clinica è indiscutibile in tutti gli ambiti disciplinari della medicina, peculiare è il significato, professionale e organizzativo, che le stesse possono assumere nello sviluppo e nella specifica applicazione alla sanità pubblica. In particolare, la sanità pubblica si caratterizza per: la forte eterogeneità nelle evidenze scientifiche disponibili (non di rado costituite solamente da studi osservazionali), l’adozione di un approccio di population health e la frequente individuazione di target costituiti da persone sane, la molteplicità (anche in relazione all’importanza attribuita dagli stakeholder coinvolti) degli ambiti di produzione di linee guida (www.who.int/publications/guidelines), degli interventi sanitari e degli outcome individuati nei contesti reali (e non di ricerca), condizionati da una molteplicità di variabili culturali, organizzative, socio-economiche e ambientali.

Spesso le raccomandazioni prodotte in sanità pubblica sono destinate ad avere un impatto quali-quantitativamente molto rilevante sul sistema sanitario e necessitano di modelli in grado di prevederne l’implementazione, non sempre agevolmente correlabili alle evidenze scientifiche disponibili a priori. Altresì, il percorso di costruzione del consenso e implementazione degli interventi è articolato e complesso. In misura maggiore rispetto ad altre discipline mediche, i comportamenti degli operatori non si basano solo sulle conoscenze tecnico-scientifiche disponibili (talora limitate e non sempre esplicitamente generalizzabili), ma risentono e sono condizionati da dettati normativi, meccanismi di consenso locale, eterogeneità di strutture erogatrici e risorse (professionali, organizzative e tecnologiche), nonché da relazioni con una molteplicità di portatori di interesse dentro e fuori il sistema sanitario (che a loro volta esprimono valori e preferenze anche contrastanti).

Il metodo scelto dal CNEC (e adottato anche dall’Agenzia Italiana del Farmaco per le valutazioni di propria competenza) per la produzione di linee guida è il metodo GRADEGrading of Recommendations Assessment, Development and Evaluation – che costituisce oggi la principale cornice riferimento per la valutazione di affidabilità delle prove scientifiche e per la formulazione di raccomandazioni cliniche basate sulle evidenze in sanità: viene utilizzato da più di 100 organizzazioni in tutto il mondo comprendenti anche l’Organizzazione Mondiale della Sanità e il National Institute for Health and Care Excellence (www.gradeworkinggroup.org). Il GRADE assicura standardizzazione e trasparenza della procedura con cui viene valutata la qualità delle prove disponibili e la forza delle raccomandazioni per la produzione di linee guida, favorendo una valutazione integrata della qualità metodologica delle prove disponibili con altri aspetti che devono essere considerati per sviluppare e stabilire la forza di una raccomandazione, mediante i cosiddetti Evidence to Decision Framework, quali: priorità della problematica trattata (es. impatto sanitario, variabilità, costi), benefici e rischi attesi, valori e preferenze dei pazienti, costo-efficacia, accettabilità, fattibilità ed equità. Il GRADE offre un approccio flessibile e pragmatico che può essere applicato sia alla produzione di una linea guida ex novo che all’adattamento di linee guida già esistenti, per le quali si applicano gli schemi di GRADE-ADOLOPMENT, calibrati su un determinato contesto culturale e organizzativo. Il panel di esperti (gruppi di lavoro multidisciplinari e multistakeholder che sistematicamente devono coinvolgere anche utenti/cittadini) definisce chiaramente la domanda di ricerca, il protocollo condiviso secondo l’acronimo PICO (Patient-Intervention-Comparator-Outcome) per l’analisi della qualità delle prove di evidenza ed esprimere giudizi sui diversi criteri di valutazione necessari alla formulazione e valutazione della forza delle raccomandazioni. Mediante una gestione trasparente (e una particolare attenzione alla disclosure e alla gestione dei conflitti di interesse dei membri dei panel), fortemente ancorata al mondo reale, con il processo di “evidence to decision” il GRADE si pone l’obiettivo di ordinare per gradi la forza delle raccomandazioni espresse dai panel di esperti in modo da offrire strumenti interpretativi e decisionali per pazienti/utenti, clinici e decisori sanitari. La rappresentatività e il coinvolgimento con modalità strutturate di tutte le figure competenti e rilevanti per i quesiti e sulle raccomandazioni in oggetto costituisce un aspetto fondamentale di qualità e credibilità della linea guida.

Accanto alla chiara affinità tra metodo GRADE e logiche epidemiologiche e di centralità di un approccio multidimensionale, multidisciplinare e inter-professionale che caratterizza il processo decisionale in sanità pubblica, è interessante evidenziare l’opportunità della promozione dell’applicazione del GRADE per gli igienisti sia nella veste di proponenti, esperti per gli ambiti tecnico-scientifici di propria competenza e destinatari “professionali” delle raccomandazioni, che in qualità di manager e decisori che possono essere coinvolti nei panel (anche su pratiche di non esclusiva pertinenza della sanità pubblica), nonché, naturalmente di metodologi, parte dei team di revisione della letteratura e a supporto dell’utilizzo del metodo stesso che richiede una specifica formazione e competenza.

Gli indirizzi sulle LG comprendono anche la fase di implementazione attinente come a partire dalle raccomandazioni prodotte e diffuse si riesce ad incidere sui comportamenti professionali, ovvero colmare il gap tra ricerca e pratica professionale. Questo richiede leadership e facilitazione del giusto mix di interventi (preferibilmente multifattoriali) di supporto al cambiamento (audit & feedback, interventi formativi mirati, processi di consenso locali, uso di strumenti di comunicazione, ecc), calibrati su ostacoli e fattori favorenti l’adozione delle linee guida. L’implementazione di LG promuove la gestione e la condivisione di informazioni, conoscenze e pratiche che favoriscono un approccio trasversale rispetto alle funzioni e ai team di lavoro che promuove l’integrazione (sia all’interno che con l’esterno delle organizzazioni sanitarie) e può assicurare processi decisionali più affidabili ed efficienti.

La coerenza tra raccomandazioni per l’ottimizzazione dell’efficacia e altre dimensioni della qualità dell’intervento sanitario (quali sicurezza, accessibilità ed equità) con le esigenze di efficienza e razionalità organizzativa dei servizi configura un importante ancoraggio delle LG al paradigma emergente del valore in sanità. Costruire una sanità basata sul valore implica una chiara analisi del profilo di efficacia degli interventi sanitari e la disponibilità di robusti strumenti valutativi e infrastrutture digitali di supporto alla misurazione accurata e tempestiva dei dati epidemiologici della popolazione, da trasformare in informazioni cliniche rilevanti per integrare e analizzare tutti i passaggi (e i risultati ottenuti) del ciclo di assistenza in oggetto e da correlare costantemente con i costi sostenuti dal sistema sanitario. Massimizzare il valore, ovvero gli esiti prodotti in relazione alle risorse a disposizione, per gli individui e le popolazioni presuppone l’adozione di criteri di finanziamento e di gestione delle risorse (umane e organizzative) e soluzioni tecnologiche che facilitino la costruzione di reti e percorsi, da coniugare con la capacità di tradurre i risultati della ricerca sanitaria e le best practice in raccomandazioni. D’altro canto, la diffusione di pratiche sicure, efficaci e appropriate consente di concorrere in maniera determinante all’uniformità di tassonomia, modelli e comportamenti professionali in contesti decisionali affini, ovvero di contribuire a standardizzare l’operatività dei servizi, aspetto quest’ultimo rilevante nel contesto della sanità pubblica italiana e delle sue articolazioni operative territoriali.

L’adozione di linee guida ovviamente presenta anche aspetti di criticità, legati all’effettiva traduzione dei risultati della ricerca e dell’innovazione in comportamenti professionali diffusi e virtuosi; ma anche all’adeguatezza delle LG e dei correlati processi decisionali di fronte a quesiti o target di popolazione per loro natura complessi, come quelli che si incontrano per esempio nel produrre indirizzi che siano effettivamente rispondenti alle esigenze di prevenzione e personalizzazione dell’assistenza del “paziente complesso”. A ciò vanno aggiunte alcune difficoltà organizzative e professionali che connotano l’odierna fase di avvio della concreta applicazione del metodo GRADE allo sviluppo delle raccomandazioni per la pratica clinica proposto nel “nuovo Sistema Nazionale Linee Guida”. Per esempio, rispetto alla sanità pubblica, pur esistendo oggi molte LG autorevoli e di diffusa applicazione, queste spesso risultano essere datate e realizzate con meccanismi di consenso e formulazione delle raccomandazioni di tipo tradizionale, rendendo dunque necessari aggiornamenti e adattamenti secondo le menzionate modalità di lavoro proposte a livello nazionale e internazionale per produrre linee guida di alta qualità.

Per operare nel quadro della nuova cornice metodologica sulle LG, ai medici e agli altri professionisti sanitari, ai manager e ai policy maker della sanità, al mondo accademico e alle società scientifiche è richiesto un investimento prioritario nella gestione di conoscenze fondate su un approccio scientifico, strutturato e trasparente alla definizione dell’efficacia e dell’appropriatezza degli interventi medici. In questo contesto nazionale, per gli igienisti in collaborazione con tutti gli attori della Sanità Pubblica, è strategico un impegno permanente sulla tematica delle linee guida, da sostenere anche mediante azioni di formazione, condivisione di conoscenza e di comunicazione. Valorizzare l’applicazione critica di strumenti per governare i processi decisionali secondo logiche di partecipazione e fiducia reciproca tra gli stakeholder è fondamentale per il perseguimento degli obiettivi di ottimizzazione della qualità e della sostenibilità nel Servizio Sanitario Nazionale, a beneficio dei cittadini-pazienti e della società nella sua globalità.

]]>
<![CDATA[Electroencephalographic Signatures of the Neural Representation of Speech during Selective Attention]]> https://www.researchpad.co/article/Na0742e59-95b8-4c35-ba95-9b75647b6dc2

Abstract

The ability to selectively attend to speech in the presence of other competing talkers is critical for everyday communication; yet the neural mechanisms facilitating this process are poorly understood. Here, we use electroencephalography (EEG) to study how a mixture of two speech streams is represented in the brain as subjects attend to one stream or the other. To characterize the speech-EEG relationships and how they are modulated by attention, we estimate the statistical association between each canonical EEG frequency band (delta, theta, alpha, beta, low-gamma, and high-gamma) and the envelope of each of ten different frequency bands in the input speech. Consistent with previous literature, we find that low-frequency (delta and theta) bands show greater speech-EEG coherence when the speech stream is attended compared to when it is ignored. We also find that the envelope of the low-gamma band shows a similar attention effect, a result not previously reported with EEG. This is consistent with the prevailing theory that neural dynamics in the gamma range are important for attention-dependent routing of information in cortical circuits. In addition, we also find that the greatest attention-dependent increases in speech-EEG coherence are seen in the mid-frequency acoustic bands (0.5–3 kHz) of input speech and the temporal-parietal EEG sensors. Finally, we find individual differences in the following: (1) the specific set of speech-EEG associations that are the strongest, (2) the EEG and speech features that are the most informative about attentional focus, and (3) the overall magnitude of attentional enhancement of speech-EEG coherence.

]]>
<![CDATA[Promoting Accrual of Older Patients with Cancer to Clinical Trials: An Alliance for Clinical Trials in Oncology Member Survey (A171602)]]> https://www.researchpad.co/article/5c8ef0bed5eed0c484f03f2c

This article describes a web‐based survey of the Alliance for Clinical Trials in Oncology membership, including physicians, nurses, patient advocates, project managers, statisticians, leadership, and administrative staff. The goal of the survey was to identify new strategies to effect change in accrual for older patients with cancer by eliciting the opinions of a national sample of the oncology clinical research workforce and patient advocates who participate in high‐impact cancer clinical research.

]]>