Corrigendum for health-related quality of life and hospitalizations in chronic thromboembolic pulmonary hypertension versus idiopathic pulmonary arterial hypertension: And analysis from the Pulmonary Hypertension Association Registry.

[This corrects the article DOI: 10.1177/20458940211053196.].

ESMO expert consensus statements on the management of EGFR mutant non-small-cell lung cancer.

The European Society for Medical Oncology (ESMO) held a virtual consensus-building process on epidermal growth factor receptor (EGFR)-mutant non-small-cell lung cancer in 2021. The consensus included a multidisciplinary panel of 34 leading experts in the management of lung cancer. The aim of the consensus was to develop recommendations on topics that are not covered in detail in the current ESMO Clinical Practice Guideline and where the available evidence is either limited or conflicting. The main topics identified for discussion were: (i) tissue and biomarkers analyses; (ii) early and locally advanced disease; (iii) metastatic disease and (iv) clinical trial design, patient's perspective and miscellaneous. The expert panel was divided into four working groups to address questions relating to one of the four topics outlined above. Relevant scientific literature was reviewed in advance. Recommendations were developed by the working groups and then presented to the entire panel for further discussion and amendment before voting. This manuscript presents the recommendations developed, including findings from the expert panel discussions, consensus recommendations and a summary of evidence supporting each recommendation.

Early-childhood social reticence predicts SCR-BOLD coupling during fear extinction recall in preadolescent youth.

Social Reticence (SR) is a temperament construct identified in early childhood that is expressed as shy, anxiously avoidant behavior and, particularly when stable, robustly associated with risk for anxiety disorders. Threat circuit function may develop differently for children high on SR than low on SR. We compared brain function and behavior during extinction recall in a sample of 11-to-15-year-old children characterized in early childhood on a continuum of SR. Three weeks after undergoing fear conditioning and extinction, participants completed a functional magnetic resonance imaging extinction recall task assessing memory and threat differentiation for conditioned stimuli. Whereas self-report and psychophysiological measures of differential conditioning, extinction, and extinction recall were largely similar across participants, SR-related differences in brain function emerged during extinction recall. Specifically, childhood SR was associated with a distinct pattern of hemodynamic-autonomic covariation in the brain when recalling extinguished threat and safety cues. SR and attention focus impacted associations between trial-by-trial variation in autonomic responding and in brain activation. These interactions occurred in three main brain areas: the anterior insular cortex (AIC), the anterior subdivision of the medial cingulate cortex (aMCC), and the dorsolateral prefrontal cortex (dlPFC). This pattern of SCR-BOLD coupling may reflect selective difficulty tracking safety in a temperamentally at-risk population.

SEIS: Insight's Seismic Experiment for Internal Structure of Mars.

By the end of 2018, 42 years after the landing of the two Viking seismometers on Mars, InSight will deploy onto Mars' surface the SEIS (Seismic Experiment for Internal Structure) instrument; a six-axes seismometer equipped with both a long-period three-axes Very Broad Band (VBB) instrument and a three-axes short-period (SP) instrument. These six sensors will cover a broad range of the seismic bandwidth, from 0.01 Hz to 50 Hz, with possible extension to longer periods. Data will be transmitted in the form of three continuous VBB components at 2 sample per second (sps), an estimation of the short period energy content from the SP at 1 sps and a continuous compound VBB/SP vertical axis at 10 sps. The continuous streams will be augmented by requested event data with sample rates from 20 to 100 sps. SEIS will improve upon the existing resolution of Viking's Mars seismic monitoring by a factor of ∼ 2500 at 1 Hz and ∼ 200 000 at 0.1 Hz. An additional major improvement is that, contrary to Viking, the seismometers will be deployed via a robotic arm directly onto Mars' surface and will be protected against temperature and wind by highly efficient thermal and wind shielding. Based on existing knowledge of Mars, it is reasonable to infer a moment magnitude detection threshold of M w ∼ 3 at 40 ∘ epicentral distance and a potential to detect several tens of quakes and about five impacts per year. In this paper, we first describe the science goals of the experiment and the rationale used to define its requirements. We then provide a detailed description of the hardware, from the sensors to the deployment system and associated performance, including transfer functions of the seismic sensors and temperature sensors. We conclude by describing the experiment ground segment, including data processing services, outreach and education networks and provide a description of the format to be used for future data distribution. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s11214-018-0574-6) contains supplementary material, which is available to authorized users.

Associations between asthma trigger reports, mental health conditions, and asthma morbidity among world trade center rescue and recovery workers.

Aim: There is limited information regarding asthma triggers in World Trade Center (WTC) rescue and recovery workers (RRW) or how mental health conditions affect the perception of triggers. Methods: We included 372 WTC workers with asthma. The Asthma Trigger Inventory (ATI) assessed triggers along five domains: psychological, allergens, physical activity, infection, and pollution. We administered the Structured Clinical Interview to diagnose post-traumatic stress disorder (PTSD), major depression and panic disorder (PD). The Asthma Control Questionnaire (ACQ) and Mini Asthma Quality of Life Questionnaire (AQLQ) measured asthma control and quality of life, respectively. Linear regression models were fitted to examine the association of ATI total and subdomain scores with mental health conditions as well as the percent of ACQ and AQLQ variance explained by ATI subscales. Results: The most common triggers were air pollution (75%) and general allergens (68%). PTSD was significantly associated with psychological triggers (partial r2=0.05, p < 0.01), physical activity (partial r2=0.03, p < 0.01) and air pollution (partial r2=0.02, p = 0.04) subscales while PD was significantly associated with air pollution (partial r2=0.03, p = 0.03) and general allergens (partial r2=0.02, p = 0.03). ATI subscales explained a large percentage of variance in asthma control (r2=0.37, p < 0.01) and quality of life scores (r2=0.40, p < 0.01). Psychological subscale scores explained the largest portion of the total variability in ACQ (partial r2= 0.11, p = 0.72) and AQLQ (partial r2=0.14, p = 0.64) scores. Conclusion: RRW with mental health conditions reported more asthma triggers and these triggers were associated with asthma morbidity. These data can help support interventions in RRW with asthma.

Facts and challenges in respiratory neurobiology.

Respiratory neurobiology has been a lead discipline in the field of neuroscience for almost a century. Despite this, research studies on the fundamental synaptic and cellular processes underlying the generation and modulation of breathing movements suffered a significant decline during the last decade. We still believe that respiratory neurobiology is one of the most exciting and imperative fields of neuroscience. With the first white paper concerned with the central control of breathing, we want to celebrate the global importance of breathing research.

A systematic review of care delivery models and economic analyses in lymphedema: health policy impact (2004-2011).

A project of the American Lymphedema Framework Project (ALFP), this review seeks to examine the policy and economic impact of caring for patients with lymphedema, a common side effect of cancer treatment. This review is the first of its kind undertaken to investigate, coordinate, and streamline lymphedema policy initiatives in the United States with potential applicability worldwide. As part of a large scale literature review aiming to systematically evaluate the level of evidence of contemporary peer-reviewed lymphedema literature (2004 to 2011), publications on care delivery models, health policy, and economic impact were retrieved, summarized, and evaluated by a team of investigators and clinical experts. The review substantiates lymphedema education models and clinical models implemented at the community, health care provider, and individual level that improve delivery of care. The review exposes the lack of economic analysis related to lymphedema. Despite a dearth of evidence, efforts towards policy initiatives at the federal and state level are underway. These initiatives and the evidence to support them are examined and recommendations for translating these findings into clinical practice are made. Medical and community-based disease management interventions, taking on a public approach, are effective delivery models for lymphedema care and demonstrate great potential to improve cancer survivorship care. Efforts to create policy at the federal, state, and local level should target implementation of these models. More research is needed to identify costs associated with the treatment of lymphedema and to model the cost outlays and potential cost savings associated with comprehensive management of chronic lymphedema.

In situ cleaning of instruments for the sensitive detection of organics on Mars.

A method is presented for in situ cleaning of spacecraft instruments that analyze planetary soil and rock. We have found that vibrating hardware, used to facilitate powder transport, was also effective at removing contamination. Surfaces can be cleaned below monolayer levels using vibrating surfaces in the presence of mineral powder. Both organic and particulate contamination is efficiently removed. Fine grained regolith from the planetary surface or an organic free reference material may serve as the powder used for cleaning. We present both analytical and experimental results for the contamination transfer fraction and the conditions required to clean the hardware prior to sensitive chemical analysis.

Intermittent pneumatic compression therapy: a systematic review.

Intermittent pneumatic compression (IPC) therapy is an effective modality to reduce the volume of the lymphedematous limbs alone or in conjunction with other modalities of therapy such as decongestive therapy. However, there is no consensus on the frequency or treatment parameters for IPC devices. We undertook a systematic review of contemporary peer-reviewed literature (2004-2011) to evaluate the evidence for use of IPC in the treatment of lymphedema. In select patients, IPC use may provide an acceptable home-based treatment modality in addition to wearing compression garments.

A preliminary randomized controlled study to determine the application frequency of a new lymphoedema bandaging system.

BACKGROUND: Bandaging plays an important role in the treatment of lymphoedema. OBJECTIVE: To investigate efficacy and safety of the 3M™ Coban™ 2 compression system (Coban 2 system) with different application frequencies in comparison to short-stretch bandaging. METHODS: A multicentre, randomized, prospective study was performed with 82 patients suffering from arm or leg lymphoedema stage II or late stage II. Patients were allocated to traditional short-stretch bandaging five times per week or to the Coban 2 system applied two, three or five times per week for 19 days. Limb volume and adverse events were recorded at each study visit. The primary endpoint was percentage volume reduction. RESULTS: The highest lymphoedema volume reduction was achieved with the Coban 2 system applied two times per week. A mean reduction of 18·7% (SD 14·5) in legs and 10·5% (SD 8·3) in arms was achieved. More frequent bandage changes of three and five times per week did not demonstrate additional benefits. Short-stretch bandaging five times per week showed a mean volume reduction of 10·9% (SD 5·2) and 8·2% (SD 3·1) for legs and arms, respectively. Bandage slippage was low for all treatment groups. A relevant change in overall mobility was achieved during the use of the Coban 2 system. The adverse reactions were in agreement with already known side-effects and did not differ remarkably between the treatment groups. CONCLUSION: The 3M™ Coban™ 2 compression system applied twice weekly demonstrated a high rate of volume reduction and a good safety profile. Oedema reduction was still effective with 4 days between bandage change, which allows a constant therapeutic effect in routine practice. This should give the patient a high degree of independence and mobility.

Perceptual comparison of features within and between objects: a new look.

The integration of spatially distinct elements into coherent objects is a fundamental process of vision. Yet notwithstanding an extensive literature on perceptual grouping, we still lack a clear understanding of the representational consequences of grouping disparate visual locations. We investigated this question in a feature comparison task; subjects identified matching features that belonged either to the same apparent object (within-object condition) or to different apparent objects (between-object condition). The stimulus was backward-masked at a variable SOA, to examine the consequences of changes in the perceptual organization of the segments over time. Critical to our aims, the two objects composing our stimulus were occluded to a variable extent, so that differences in within-object and between-object performance could be unequivocally related to the formation of objects. For certain stimulus arrangements, we found superior performance for within-object matches. The pattern of performance was, however, highly dependent on the stimulus orientation and was not related to the strength of the object percept. Using an oblique stimulus arrangement, we observed superior between-object comparisons that did vary with the object percept. We conclude that performance in our feature comparison task is strongly influenced by spatial relations between features that are independent of object properties. Indeed, this dominating effect may hide an underlying mechanism whereby formation of a visual object suppresses comparison of distinct features within the object.

High thermal conductivity of a hydrogenated amorphous silicon film.

We measured the thermal conductivity kappa of an 80 microm thick hydrogenated amorphous silicon film prepared by hot-wire chemical-vapor deposition with the 3omega (80-300 K) and the time-domain thermo-reflectance (300 K) methods. The kappa is higher than any of the previous temperature dependent measurements and shows a strong phonon mean free path dependence. We also applied a Kubo based theory using a tight-binding method on three 1000 atom continuous random network models. The theory gives higher kappa for more ordered models, but not high enough to explain our results, even after extrapolating to lower frequencies with a Boltzmann approach. Our results show that this material is more ordered than any amorphous silicon previously studied.

Vibron hopping and bond anharmonicity in hot dense hydrogen.

The Raman-active vibron of dense hydrogen has been shown to exhibit unexpected changes as a function of pressure and temperature to above 100 GPa. To understand these results we have performed supercell-based calculations using Van Kranendonk theory taking into account the renormalization of the hopping parameter by the lattice vibrations. We find that the major temperature dependence at this level of theory comes from the differences in populations of rotational states. The theory provides a fair description of the experimental results up to 70 GPa. We examine in detail a number of assumptions made in the application of the Van Kranendonk model to hydrogen as a function of pressure and temperature. We also present results of hybrid path integral molecular dynamics calculations in the fluid state at a low pressure (7 GPa) near the melting temperature. An amorphous-solid model of the fluid predicts that the Raman vibron frequencies change little upon melting, in agreement with experiment. The Van Kranendonk theory with fixed rotational identities of the molecules tends to predict more peaks in the Raman spectrum than are observed experimentally.

Cholinergic neurotransmission in the preBötzinger Complex modulates excitability of inspiratory neurons and regulates respiratory rhythm.

We investigated whether there is endogenous acetylcholine (ACh) release in the preBötzinger Complex (preBötC), a medullary region hypothesized to contain neurons generating respiratory rhythm, and how endogenous ACh modulates preBötCneuronal function and regulates respiratory pattern. Using a medullary slice preparation from neonatal rat, we recorded spontaneous respiratory-related rhythm from the hypoglossal nerve roots (XIIn) and patch-clamped preBötC inspiratory neurons. Unilateral microinjection of physostigmine, an acetylcholinesterase inhibitor, into the preBötC increased the frequency of respiratory-related rhythmic activity from XIIn to 116+/-13% (mean+/-S.D.) of control. Ipsilateral physostigmine injection into the hypoglossal nucleus (XII nucleus) induced tonic activity, increased the amplitude and duration of the integrated inspiratory bursts of XIIn to 122+/-17% and 117+/-22% of control respectively; but did not alter frequency. In preBötC inspiratory neurons, bath application of physostigmine (10 microM) induced an inward current of 6.3+/-10.6 pA, increased the membrane noise, decreased the amplitude of phasic inspiratory drive current to 79+/-16% of control, increased the frequency of spontaneous excitatory postsynaptic currents to 163+/-103% and decreased the whole cell input resistance to 73+/-22% of control without affecting the threshold for generation of action potentials. Bath application of physostigmine concurrently induced tonic activity, increased the frequency, amplitude and duration of inspiratory bursts of XIIn motor output. Bath application of 4-diphenylacetoxy-N-methylpiperidine methiodide (4-DAMP, 2 microM), a M3 muscarinic acetylcholine receptor (mAChR) selective antagonist, increased the input resistance of preBötC inspiratory neurons to 116+/-9% of control and blocked all of the effects of physostigmine except for the increase in respiratory frequency. Dihydro-beta-erythroidine (DH-beta-E; 0.2 microM), an alpha4beta2 nicotinic receptor (nAChR) selective antagonist, blocked all the effects of physostigmine except for the increase in inspiratory burst amplitude. In the presence of both 4-DAMP and DH-beta-E, physostigmine induced opposite effects, i.e. a decrease in frequency and amplitude of XIIn rhythmic activity. These results suggest that there is cholinergic neurotransmission in the preBötC which regulates respiratory frequency, and in XII nucleus which regulates tonic activity, and the amplitude and duration of inspiratory bursts of XIIn in neonatal rats. Physiologically relevant levels of ACh release, via mAChRs antagonized by 4-DAMP and nAChRs antagonized by DH-beta-E, modulate the excitability of inspiratory neurons and excitatory neurotransmission in the preBötC, consequently regulating respiratory rhythm.

Aberrant auditory processing and atypical planum temporale in developmental stuttering.

OBJECTIVE: To learn if people with persistent developmental stuttering and atypical anatomy of their auditory temporal cortex have, when compared to control subjects, changes in fluency induced with delayed auditory feedback (DAF). BACKGROUND: DAF improves fluency in many individuals who stutter, and induces dysfluency in some normal people. The planum temporale (PT), a portion of auditory temporal cortex, is anatomically atypical in some adults who stutter and atypical anatomy might induce aberrant function. Thus, the people who demonstrate the paradoxical response to DAF might be those who have atypical anatomy. METHODS: Experimental subjects were adults with developmental stuttering (n = 14) and control subjects (n = 14) matched for age, sex, education, and handedness. Volumetric MRI scans of all subjects were obtained and the PT was measured in the right and left hemispheres. Based on these scans, subjects were classified as typical (leftward PT asymmetry) or atypical (rightward PT asymmetry). Prose passages were read at baseline, with non-altered feedback (NAF), and with DAF, and fluency was measured in these three conditions. RESULTS: At baseline the adults with developmental stuttering were significantly more dysfluent than controls (p < 0.0005). Controls' fluency did not significantly change with DAF, but DAF improved fluency in adults with developmental stuttering (p < 0.0005). In the stutter group enhanced fluency was associated with atypical (rightward) PT asymmetry, and the presence of typical (leftward) PT asymmetry was not associated with any significant change in fluency. The individuals with atypical PT asymmetry also had more severe stuttering at baseline compared to the experimental subjects with typical PT anatomy. CONCLUSIONS: In adults with persistent developmental stuttering and atypical PT anatomy, fluency is improved with DAF. These experimental subjects who showed improvement had more severe stuttering at baseline. Anomalous PT anatomy may be a neural risk for developmental stuttering in some individuals. Although a number of explanations are tenable, it may be that atypical rightward PT asymmetry may alter speech feedback, and treatment with DAF might allow these people to compensate.

Incident hepatitis C virus in women with human immunodeficiency virus infection.

Individuals infected with human immunodeficiency virus type 1 (HIV-1) are frequently coinfected with hepatitis C virus (HCV). Acute HCV infection is often asymptomatic and poorly understood. We conducted a historical prospective study of HCV antibody and viremia in plasma samples obtained during 1994-1999 from a cohort of initially HIV-1-infected, HCV-uninfected women and from HIV-1-HCV-uninfected women. Twenty-two (1.5%) of 1517 experienced seroconversion. Of these, 14 (64%) truly acquired a new infection as assessed by enzyme immunoassay response and new-onset viremia. The incidence rate in HIV-1-infected women was 2.7 cases per 1000 person-years; it was 3.3 cases per 1000 person-years in HIV-1-seronegative women (relative risk, 1.21; P=.75). Acquisition of HCV was associated with any history of drug use (P<.01). Five of 12 viremic, seroconverting individuals cleared viremia. Incident HCV infection among HIV-1-infected and HIV-1-uninfected women was low. It was linked to drug use and commonly resolved.

Protective effects of centrally acting sympathomodulatory drugs on myocardial ischemia induced by sympathetic overactivity in rabbits.

It is recognized that an imbalance of the autonomic nervous system is involved in the genesis of ventricular arrhythmia and sudden death during myocardial ischemia. In the present study we investigated the effects of clonidine and rilmenidine, two centrally acting sympathomodulatory drugs, on an experimental model of centrally induced sympathetic hyperactivity in pentobarbital-anesthetized New Zealand albino rabbits of either sex (2-3 kg, N = 89). We also compared the effects of clonidine and rilmenidine with those of propranolol, a beta-blocker, known to induce protective cardiovascular effects in patients with ischemic heart disease. Central sympathetic stimulation was achieved by intracerebroventricular injection of the excitatory amino acid L-glutamate (10 micro mol), associated with inhibition of nitric oxide synthesis with L-NAME (40 mg/kg, iv). Glutamate triggered ventricular arrhythmia and persistent ST-segment shifts in the ECG, indicating myocardial ischemia. The intracisternal administration of clonidine (1 microg/kg) and rilmenidine (30 microg/kg) or of a nonhypotensive dose of rilmenidine (3 microg/kg) decreased the incidence of myocardial ischemia (25, 14 and 25%, respectively, versus 60% in controls) and reduced the mortality rate from 40% to 0.0, 0.0 and 12%, respectively. The total number of ventricular premature beats per minute fell from 30 +/- 9 in the control group to 7 +/- 3, 6 +/- 3 and 2 +/- 2, respectively. Intravenous administration of clonidine (10 micro g/kg), rilmenidine (300 microg/kg) or propranolol (500 microg/kg) elicited similar protective effects. We conclude that clonidine and rilmenidine present cardioprotective effects of central origin, which can be reproduced by propranolol, a lipophilic beta-blocking agent.