A multi-compartment model for interneurons in the dorsal lateral geniculate nucleus

GABAergic interneurons (INs) in the dorsal lateral geniculate nucleus (dLGN) shape the information flow from retina to cortex, presumably by controlling the number of visually evoked spikes in geniculate thalamocortical (TC) neurons, and refining their receptive field. The INs exhibit a rich variety of firing patterns: Depolarizing current injections to the soma may induce tonic firing, periodic bursting or an initial burst followed by tonic spiking, sometimes with prominent spike-time adaptation. When released from hyperpolarization, some INs elicit rebound bursts, while others return more passively to the resting potential. A full mechanistic understanding that explains the function of the dLGN on the basis of neuronal morphology, physiology and circuitry is currently lacking. One way to approach such an understanding is by developing a detailed mathematical model of the involved cells and their interactions. Limitations of the previous models for the INs of the dLGN region prevent an accurate representation of the conceptual framework needed to understand the computational properties of this region. We here present a detailed compartmental model of INs using, for the first time, a morphological reconstruction and a set of active dendritic conductances constrained by experimental somatic recordings from INs under several different current-clamp conditions. The model makes a number of experimentally testable predictions about the role of specific mechanisms for the firing properties observed in these neurons. In addition to accounting for the significant features of all experimental traces, it quantitatively reproduces the experimental recordings of the action-potential- firing frequency as a function of injected current. We show how and why relative differences in conductance values, rather than differences in ion channel composition, could account for the distinct differences between the responses observed in two different neurons, suggesting that INs may be individually tuned to optimize network operation under different input conditions

Sofosbuvir based treatment of chronic hepatitis C genotype 3 infections-A Scandinavian real-life study

Background and aims Chronic hepatitis C virus (HCV) genotype 3 infection with advanced liver disease has emerged as the most challenging to treat. We retrospectively assessed the treatment outcome of sofosbuvir (SOF) based regimes for treatment of HCV genotype 3 infections in a real life setting in Scandinavia. Methods Consecutive patients with chronic HCV genotype 3 infection were enrolled at 16 treatment centers in Denmark, Sweden, Norway and Finland. Patients who had received a SOF containing regimen were included. The fibrosis stage was evaluated by liver biopsy or transient liver elastography. The following treatments were given according availability and local guidelines: 1) SOF + ribavirin (RBV) for 24 weeks, 2) SOF + daclatasvir (DCV) +/-RBV for 12-24 weeks, 3) SOF + pegylated interferon alpha (peg-IFN-a) + RBV for 12 weeks or 4) SOF/ledipasvir (LDV) + RBV for 12-16 weeks. The primary endpoint was sustained virological response (SVR) assessed at week 12 (SVR12) after end of treatment. Results We included 316 patients with a mean age of 55 years (range 24-79), 70% men, 49% treatment experienced, 58% with compensated cirrhosis and 12% with decompensated cirrhosis. In the modified intention to treat (mITT) population SVR12 was achieved in 284/311 91%) patients. Among 26 treatment failures, five had non-response, 3 breakthrough and 18 relapse. Five patients were not included in the mITT population. Three patients died from reasons unrelated to treatment and two were lost to follow-up. The SVR12 rate was similar for all treatment regimens, but lower in men (p = 0.042), and in patients with decompensated liver disease (p = 0.004). Conclusion We found that sofosbuvir based treatment in a real-life setting could offer SVR rates exceeding 90% in patients with HCV genotype 3 infection and advanced liver disease.Peer reviewe

Fiskeriakustikk og akustisk målklassifisering - Rapport frå COGMAR/CRIMAC arbeidsmøte om maskinlæring og fiskeriakustikk

Source at https://www.hi.no/hi/nettrapporter/rapport-fra-havforskningen-en-2021-25This report documents a workshop organised by the COGMAR and CRIMAC projects. The objective of the workshop was twofold. The first objective was to give an overview of ongoing work using machine learning for Acoustic Target Classification (ATC). Machine learning methods, and in particular deep learning models, are currently being used across a range of different fields, including ATC. The objective was to give an overview of the status of the work. The second objective was to familiarise participants with machine learning background to fisheries acoustics and to discuss a way forward towards a standard framework for sharing data and code. This includes data standards, standard processing steps and algorithms for efficient access to data for machine learning frameworks. The results from the discussion contributes to the process in ICES for developing a community standard for fisheries acoustics data

The Changing Landscape for Stroke\ua0Prevention in AF: Findings From the GLORIA-AF Registry Phase 2

Background GLORIA-AF (Global Registry on Long-Term Oral Antithrombotic Treatment in Patients with Atrial Fibrillation) is a prospective, global registry program describing antithrombotic treatment patterns in patients with newly diagnosed nonvalvular atrial fibrillation at risk of stroke. Phase 2 began when dabigatran, the first non\u2013vitamin K antagonist oral anticoagulant (NOAC), became available. Objectives This study sought to describe phase 2 baseline data and compare these with the pre-NOAC era collected during phase 1. Methods During phase 2, 15,641 consenting patients were enrolled (November 2011 to December 2014); 15,092 were eligible. This pre-specified cross-sectional analysis describes eligible patients\u2019 baseline characteristics. Atrial fibrillation disease characteristics, medical outcomes, and concomitant diseases and medications were collected. Data were analyzed using descriptive statistics. Results Of the total patients, 45.5% were female; median age was 71 (interquartile range: 64, 78) years. Patients were from Europe (47.1%), North America (22.5%), Asia (20.3%), Latin America (6.0%), and the Middle East/Africa (4.0%). Most had high stroke risk (CHA2DS2-VASc [Congestive heart failure, Hypertension, Age  6575 years, Diabetes mellitus, previous Stroke, Vascular disease, Age 65 to 74 years, Sex category] score  652; 86.1%); 13.9% had moderate risk (CHA2DS2-VASc = 1). Overall, 79.9% received oral anticoagulants, of whom 47.6% received NOAC and 32.3% vitamin K antagonists (VKA); 12.1% received antiplatelet agents; 7.8% received no antithrombotic treatment. For comparison, the proportion of phase 1 patients (of N = 1,063 all eligible) prescribed VKA was 32.8%, acetylsalicylic acid 41.7%, and no therapy 20.2%. In Europe in phase 2, treatment with NOAC was more common than VKA (52.3% and 37.8%, respectively); 6.0% of patients received antiplatelet treatment; and 3.8% received no antithrombotic treatment. In North America, 52.1%, 26.2%, and 14.0% of patients received NOAC, VKA, and antiplatelet drugs, respectively; 7.5% received no antithrombotic treatment. NOAC use was less common in Asia (27.7%), where 27.5% of patients received VKA, 25.0% antiplatelet drugs, and 19.8% no antithrombotic treatment. Conclusions The baseline data from GLORIA-AF phase 2 demonstrate that in newly diagnosed nonvalvular atrial fibrillation patients, NOAC have been highly adopted into practice, becoming more frequently prescribed than VKA in Europe and North America. Worldwide, however, a large proportion of patients remain undertreated, particularly in Asia and North America. (Global Registry on Long-Term Oral Antithrombotic Treatment in Patients With Atrial Fibrillation [GLORIA-AF]; NCT01468701

Reduced peak oxygen uptake and implications for cardiovascular health and quality of life in patients with schizophrenia

Background: Peak oxygen uptake (VO2peak) is a strong predictor of cardiovascular disease (CVD) and all-cause mortality, but is inadequately described in patients with schizophrenia. The aim of this study was to evaluate treadmill VO2peak, CVD risk factors and quality of life (QOL) in patients with schizophrenia (ICD-10, F20-29). Methods: 33 patients, 22 men (33.7 ± 10.4 years) and 11 women (35.9 ± 11.5 years), were included. Patients VO2peak were compared with normative VO2peak in healthy individuals from the Nord-Trøndelag Health Study (HUNT). Risk factors were compared above and below the VO2peak thresholds; 44.2 and 35.1 ml·kg-1·min-1 in men and women, respectively. Results: VO2peak was 37.1 ± 9.2 ml·kg-1·min-1 in men with schizophrenia; 74 ± 19% of normative healthy men (p < 0.001). VO2peak was 35.6 ± 10.7 ml·kg-1·min-1 in women with schizophrenia; 89 ± 25% of normative healthy women (n.s.). Based on odds ratio patients were 28.3 (95% CI = 1.6-505.6) times more likely to have one or more CVD risk factors if they were below the VO2peak thresholds. VO2peak correlated with the SF-36 physical functioning (r = 0.58), general health (r = 0.53), vitality (r = 0.47), social function (r = 0.41) and physical component score (r = 0.51). Conclusion: Men with schizophrenia have lower VO2peak than the general population. Patients with the lowest VO2peak have higher odds of having one or more risk factors for cardiovascular disease. VO2peak should be regarded as least as important as the conventional risk factors for CVD and evaluation of VO2peak should be incorporated in clinical practice

Therapeutic effects of maximal strength training on walking efficiency in patients with schizophrenia - a pilot study

Background Patients with schizophrenia frequently have disabling gait deficits. The net mechanical efficiency of walking (ϵ net ) is an accurate measure often used to evaluate walking performance. Patients with gait deficits have a reduced ϵ net with excessive energy expenditure during sub-maximal walking. Maximal strength training (MST) improves ϵ net in healthy individuals and is associated with reduced risk of mortality. The aim of this study was to investigate whether MST improves ϵ net in patients with schizophrenia. Methods Patients (ICD-10 schizophrenia, schizotypal or delusional disorders (F20-F29)) were included in a non-randomized trial. Patients were assigned to one of two groups: 1) MST consisting of 4x4 repetitions at 85-90% one repetition maximum (1RM) performed in a leg press apparatus or 2) playing computer games (CG). Both groups carried out their activity three days per week for eight weeks. 1RM, ϵ net at 60 watt walking, peak oxygen uptake (VO2peak), the Positive and Negative Syndrome Scale (PANSS) and the 36-items short form (SF-36) were measured pre and post intervention. Results The baseline ϵ net was 17.3 ± 1.2% and 19.4 ± 3.0% in the MST (n = 6) and CG groups (n = 7), respectively, which is categorized as mechanical inefficiency. The MST group improved 1RM by 79 kg (p = 0.006) and ϵ net by 3.4% (p = 0.046) more than the CG group. The MST group improved 1RM and ϵ net , by a mean of 83 kg (p = 0.028) and 3.4% (p = 0.028), respectively. VO2peak at baseline was 34.2 ± 10.2 and 38.3 ± 9.8 ml·kg-1·min-1 in the MST and CG groups, respectively, and did not change (p > 0.05). No change was observed in PANSS or SF-36 (p > 0.05). Conclusions MST improves 1RM and ϵ net in patients with schizophrenia. MST could be used as a therapeutic intervention for patients with schizophrenia to normalize their reduced ϵ net

Therapeutic effects of maximal strength training on walking efficiency in patients with schizophrenia – a pilot study

Abstract Background Patients with schizophrenia frequently have disabling gait deficits. The net mechanical efficiency of walking (ϵnet) is an accurate measure often used to evaluate walking performance. Patients with gait deficits have a reduced ϵnet with excessive energy expenditure during sub-maximal walking. Maximal strength training (MST) improves ϵnet in healthy individuals and is associated with reduced risk of mortality. The aim of this study was to investigate whether MST improves ϵnet in patients with schizophrenia. Methods Patients (ICD-10 schizophrenia, schizotypal or delusional disorders (F20-F29)) were included in a non-randomized trial. Patients were assigned to one of two groups: 1) MST consisting of 4x4 repetitions at 85-90% one repetition maximum (1RM) performed in a leg press apparatus or 2) playing computer games (CG). Both groups carried out their activity three days per week for eight weeks. 1RM, ϵnet at 60 watt walking, peak oxygen uptake (VO2peak), the Positive and Negative Syndrome Scale (PANSS) and the 36-items short form (SF-36) were measured pre and post intervention. Results The baseline ϵnet was 17.3 ± 1.2% and 19.4 ± 3.0% in the MST (n = 6) and CG groups (n = 7), respectively, which is categorized as mechanical inefficiency. The MST group improved 1RM by 79 kg (p = 0.006) and ϵnet by 3.4% (p = 0.046) more than the CG group. The MST group improved 1RM and ϵnet, by a mean of 83 kg (p = 0.028) and 3.4% (p = 0.028), respectively. VO2peak at baseline was 34.2 ± 10.2 and 38.3 ± 9.8 ml·kg-1·min-1 in the MST and CG groups, respectively, and did not change (p > 0.05). No change was observed in PANSS or SF-36 (p > 0.05). Conclusions MST improves 1RM and ϵnet in patients with schizophrenia. MST could be used as a therapeutic intervention for patients with schizophrenia to normalize their reduced ϵnet.</p

Mechanisms behind rebound bursting.

<p>All panels show responses to strong hyperpolarizing synaptic input (50 synapses, activated with 10 ms intervals, during 300 ms). Rebound bursts were not elicited by P1 (<b>A1</b>) or P2 (<b>A2</b>), starting from their normal resting potentials of -63 mV and -69 mV, respectively. From a -57 mV holding potential, P1 (<b>B1</b>) elicited a rebound burst following hyperpolarization, while P2 did not (<b>B2</b>). Interchanging either the <i>I_h</i> conductance (<b>C</b>) or the <i>Ca_T</i> conductance (<b>D</b>) between P1 and P2, leaving all other parameters the same, reduced the rebound response in P1, and increased it in P2. Interchanging both the <i>I_h</i> and <i>Ca_T</i> conductances between P1 and P2, also interchanged their bursting abilities completely (<b>E</b>). The scale bar applies to all panels. When conductance values were changed, the resting potential was kept at the original level by small compensatory current injections.</p

Experimental data.

<p>Somatic voltage responses in IN1, resting at -63 mV (<b>A1</b>), and IN2, resting at -69 mV (<b>A2</b>) to 7 current pulses of different intensity. When IN1 was held at -57 mV, a strong hyperpolarizing current injection was followed by a rebound burst (<b>B1</b>). When IN2 was held at -58 mV, a strong hyperpolarizing current injection did not cause a burst (<b>B2</b>). Current injections were applied as 900 ms step pulses to the soma, with intensities as indicated below the traces. Two repetitions were made of each CC-experiment, whereof one is shown. The voltage scale bar applies to all panels (A-B). <i>I_h</i> was measured at different potentials from -130 mV with 5 mV steps, in three different neurons. Recordings are shown for one neuron (<b>C</b>).</p