The Association Between Tobacco Use and Risk of COVID-19 Infection and Clinical Outcomes in Sweden: A Population-Based Study.

Background: The association between tobacco use and COVID-19 is controversial. During the early course of the pandemic, limited testing prevented studying a wide spectrum of clinical manifestations. Objective: To examine the potential causal association between tobacco use and COVID-19 during the second wave (1 October 2020-30 June 2021) of the pandemic in Stockholm, Sweden. Methods: A population-based cohort study was conducted in the Stockholm region of Sweden, with information on tobacco use collected prior to the pandemic. Adjusted relative risks (RR) of COVID-19 and 95% confidence intervals (CI) were calculated, contrasting current smokers and snus users to non-users of tobacco. Results: Compared with non-users of tobacco, current smokers had a lower risk of COVID-19 (RR 0.78, 95% CI = 0.75-0.81) and of hospitalisation for the disease. Current snus users had a higher risk of COVID-19. Heavy smokers and snus users had longer hospital stays than non-users of tobacco. Conclusion: Tobacco use may have a different impact on the risk of being infected with SARS-CoV-2 and the risk of developing severe clinical manifestations. Further research is needed to determine the underlying mechanisms.

Current tobacco use and COVID-19 diagnoses in a cohort of adult clients of public dental clinics in Sweden.

Smoking has been linked with both increased and decreased risk of COVID-19, prompting the hypothesis of a protective role of nicotine in the pathogenesis of the disease. Studies of the association between use of smokeless tobacco and COVID-19 would help refining this hypothesis. We analysed data from 424,386 residents in the Stockholm Region, Sweden, with information on smoking and smokeless tobacco (snus) use prior to the pandemic obtained from dental records. Diagnoses of COVID-19 between February and October 2020 were obtained from health-care registers. We estimated the risk of receiving a diagnosis of COVID-19 for current smokers and for current snus users relative to non-users of tobacco, adjusting for potential confounders (aRR). The aRR of COVID -19 was elevated for current snus users (1.09 ;95%CI = 0.99-1.21 among men and 1.15; 95%CI = 1.00-1.33 among women). The risk for women consuming more than 1 can/day was twice as high as among non-users of tobacco. Current smoking was negatively associated with risk of COVID-19 (aRR = 0.68; 95% CI = 0.61-0.75); including hospital admission (aRR = 0.60; 95% CI = 0.47-0.76) and intensive care (aRR = 0.43; 95% CI = 0.21-0.89). The hypothesis of a protective effect of tobacco nicotine on COVID-19 was not supported by the findings. The negative association between smoking and COVID-19 remains unexplained.

The InSight HP3 Penetrator (Mole) on Mars: Soil Properties Derived from the Penetration Attempts and Related Activities.

The NASA InSight Lander on Mars includes the Heat Flow and Physical Properties Package HP3 to measure the surface heat flow of the planet. The package uses temperature sensors that would have been brought to the target depth of 3-5 m by a small penetrator, nicknamed the mole. The mole requiring friction on its hull to balance remaining recoil from its hammer mechanism did not penetrate to the targeted depth. Instead, by precessing about a point midway along its hull, it carved a 7 cm deep and 5-6 cm wide pit and reached a depth of initially 31 cm. The root cause of the failure - as was determined through an extensive, almost two years long campaign - was a lack of friction in an unexpectedly thick cohesive duricrust. During the campaign - described in detail in this paper - the mole penetrated further aided by friction applied using the scoop at the end of the robotic Instrument Deployment Arm and by direct support by the latter. The mole tip finally reached a depth of about 37 cm, bringing the mole back-end 1-2 cm below the surface. It reversed its downward motion twice during attempts to provide friction through pressure on the regolith instead of directly with the scoop to the mole hull. The penetration record of the mole was used to infer mechanical soil parameters such as the penetration resistance of the duricrust of 0.3-0.7 MPa and a penetration resistance of a deeper layer ( > 30 cm depth) of 4.9 ± 0.4 MPa . Using the mole's thermal sensors, thermal conductivity and diffusivity were measured. Applying cone penetration theory, the resistance of the duricrust was used to estimate a cohesion of the latter of 2-15 kPa depending on the internal friction angle of the duricrust. Pushing the scoop with its blade into the surface and chopping off a piece of duricrust provided another estimate of the cohesion of 5.8 kPa. The hammerings of the mole were recorded by the seismometer SEIS and the signals were used to derive P-wave and S-wave velocities representative of the topmost tens of cm of the regolith. Together with the density provided by a thermal conductivity and diffusivity measurement using the mole's thermal sensors, the elastic moduli were calculated from the seismic velocities. Using empirical correlations from terrestrial soil studies between the shear modulus and cohesion, the previous cohesion estimates were found to be consistent with the elastic moduli. The combined data were used to derive a model of the regolith that has an about 20 cm thick duricrust underneath a 1 cm thick unconsolidated layer of sand mixed with dust and above another 10 cm of unconsolidated sand. Underneath the latter, a layer more resistant to penetration and possibly containing debris from a small impact crater is inferred. The thermal conductivity increases from 14 mW/m K to 34 mW/m K through the 1 cm sand/dust layer, keeps the latter value in the duricrust and the sand layer underneath and then increases to 64 mW/m K in the sand/gravel layer below. Supplementary Information: The online version contains supplementary material available at 10.1007/s11214-022-00941-z.

Smaller hippocampal volume following sexual assault in women is associated with post-traumatic stress disorder.

OBJECTIVE: Exposure to sexual assault is a significant risk factor to develop post-traumatic stress disorder (PTSD) in females. The early neurobiological changes leading to the development of PTSD remain understudied and unclear in this population. METHODS: Participants were 27 adult females recruited within a month following exposure to sexual assault (T1) and 20 age-matched non-exposed controls. Among the victims, 10 participants met (PTSD+) and 15 did not meet (PTSD-) DSM-IV criteria for PTSD 6 months post-trauma (T2). At both visits, hippocampal and amygdala volumes were extracted from magnetic resonance imaging scans, and indices of total diurnal cortisol changes were derived from individual areas under the curve relative to the ground (AUCg). Measures at T1 were compared between groups at T1, measures at T2 between groups at T2, and measures at T1 between groups at T2. RESULTS: At T1, victims had significantly smaller bilateral hippocampal volumes, but not AUCg, than controls. At T2, neither hippocampal volume nor AUCg significantly differed among the groups. However, the PTSD+ group had significantly smaller hippocampal volumes at T1 than the control group, but not compared to the PTSD- group. CONCLUSIONS: This study indicates that having smaller hippocampal volumes is a risk factor to develop PTSD in females exposed to sexual assault.

Reduction in resource use with the misoprostol vaginal insert vs the dinoprostone vaginal insert for labour induction: a model-based analysis from a United Kingdom healthcare perspective.

BACKGROUND: In view of the increasing pressure on the UK's maternity units, new methods of labour induction are required to alleviate the burden on the National Health Service, while maintaining the quality of care for women during delivery. A model was developed to evaluate the resource use associated with misoprostol vaginal inserts (MVIs) and dinoprostone vaginal inserts (DVIs) for the induction of labour at term. METHODS: The one-year Markov model estimated clinical outcomes in a hypothetical cohort of 1397 pregnant women (parous and nulliparous) induced with either MVI or DVI at Southmead Hospital, Bristol, UK. Efficacy and safety data were based on published and unpublished results from a phase III, double-blind, multicentre, randomised controlled trial. Resource use was modelled using data from labour induction during antenatal admission to patient discharge from Southmead Hospital. The model's sensitivity to key parameters was explored in deterministic multi-way and scenario-based analyses. RESULTS: Over one year, the model results indicated MVI use could lead to a reduction of 10,201 h (28.9%) in the time to vaginal delivery, and an increase of 121% and 52% in the proportion of women achieving vaginal delivery at 12 and 24 h, respectively, compared with DVI use. Inducing women with the MVI could lead to a 25.2% reduction in the number of midwife shifts spent managing labour induction and 451 fewer hospital bed days. These resource utilisation reductions may equate to a potential 27.4% increase in birthing capacity at Southmead Hospital, when using the MVI instead of the DVI. CONCLUSIONS: Resource use, in addition to clinical considerations, should be considered when making decisions about labour induction methods. Our model analysis suggests the MVI is an effective method for labour induction, and could lead to a considerable reduction in resource use compared with the DVI, thereby alleviating the increasing burden of labour induction in UK hospitals.

The initial stage of reversal learning is impaired in mice hemizygous for the vesicular glutamate transporter (VGluT1).

Behavioral flexibility is a complex cognitive function that is necessary for survival in changeable environments. Patients with schizophrenia or Parkinson's disease often suffer from cognitive rigidity, reducing their capacity to function in society. Patients and rodent models with focal lesions in the prefrontal cortex (PFC) show similar rigidity, owing to the loss of PFC regulation of subcortical reward circuits involved in behavioral flexibility. The vesicular glutamate transporter (VGluT1) is preferentially expressed at modulatory synapses, including PFC neurons that project to components of the reward circuit (such as the nucleus accumbens, NAc). VGluT1(+/-) mice display behavioral phenotypes matching many symptoms of schizophrenia, and VGluT1 expression is reduced in the PFC of patients with schizophrenia and Parkinson's disease. Thus, it appears likely that VGluT1-expressing synapses from PFC play a key role in behavioral flexibility. To examine this hypothesis, we studied behavioral flexibility in VGluT1(+/-) mice by testing reversal learning in a visual discrimination task. Here, we show that VGluT1(+/-) mice acquired the initial visual discrimination at the same rate as controls. However, they failed to suppress responses to the previously rewarded stimulus following reversal of reward contingencies. Thus, our genetic disruption of modulatory glutamatergic signaling, including that arising from PFC, appears to have impaired the first stage of reversal learning (extinguishing responses to previously rewarded stimuli). Our data show that this deficit stems from a preservative phenotype. These findings suggest that glutamatergic regulation from the cortex is important for behavioral flexibility and the disruption of this pathway may be relevant in diseases such as schizophrenia.

fMRI investigation of visual change detection in adults with autism.

People with autism spectrum disorders (ASD) may show unusual reactions to unexpected changes that appear in their environment. Although several studies have highlighted atypical auditory change processing in ASD, little is known in this disorder about the brain processes involved in visual automatic change detection. The present fMRI study was designed to localize brain activity elicited by unexpected visual changing stimuli in adults with ASD compared to controls. Twelve patients with ASD and 17 healthy adults participated in the experiment in which subjects were presented with a visual oddball sequence while performing a concurrent target detection task. Combined results across participants highlight the involvement of both occipital (BA 18/19) and frontal (BA 6/8) regions during visual change detection. However, adults with ASD display greater activity in the bilateral occipital cortex and in the anterior cingulate cortex (ACC) associated with smaller activation in the superior and middle frontal gyri than controls. A psychophysiological interaction (PPI) analysis was performed with ACC as the seed region and revealed greater functionally connectivity to sensory regions in ASD than in controls, but less connectivity to prefrontal and orbito-frontal cortices. Thus, compared to controls, larger sensory activation associated with reduced frontal activation was seen in ASD during automatic visual change detection. Atypical psychophysiological interactions between frontal and occipital regions were also found, congruent with the idea of atypical connectivity between these regions in ASD. The atypical involvement of the ACC in visual change detection can be related to abnormalities previously observed in the auditory modality, thus supporting the hypothesis of an altered general mechanism of change detection in patients with ASD that would underlie their unusual reaction to change.

Cerebral functional asymmetry and phonological performance in dyslexic adults.

Developmental dyslexia is a frequent language-based learning disorder characterized by difficulty in reading. The predominant etiologic view postulates that reading impairment is related to phonological and orthographic dysfunction. The aim of this fMRI study was to evaluate the neural bases of phonological processing impairment in remediated dyslexic adults (DD). We used a rhyming words judgment task contrasted with an unreadable fonts font-matching judgment task to compare patterns of activation and functional asymmetry in DD and normal-reading young adults. We found evidence of a link between asymmetry in inferior frontal gyrus and performance during the phonological processing. We also observed that DD recruit a network including regions involved in articulatory control in order to achieve rhyme judgment suggesting that, due to a lack of hemispheric specialization, DD recruit the latter network to achieve rhyme judgment.

Brain correlates of automatic visual change detection.

A number of studies support the presence of visual automatic detection of change, but little is known about the brain generators involved in such processing and about the modulation of brain activity according to the salience of the stimulus. The study presented here was designed to locate the brain activity elicited by unattended visual deviant and novel stimuli using fMRI. Seventeen adult participants were presented with a passive visual oddball sequence while performing a concurrent visual task. Variations in BOLD signal were observed in the modality-specific sensory cortex, but also in non-specific areas involved in preattentional processing of changing events. A degree-of-deviance effect was observed, since novel stimuli elicited more activity in the sensory occipital regions and at the medial frontal site than small changes. These findings could be compared to those obtained in the auditory modality and might suggest a "general" change detection process operating in several sensory modalities.

Functional morphological imaging of autism spectrum disorders: current position and theories proposed.

Autism is a pervasive disorder of childhood development. Polymorphous clinical profiles combining various degrees of communication and social interaction with restricted and stereotyped behaviour are grouped under the heading of 'autism spectrum disorders' (ASD). Many teams are trying to pick out the underlying cerebral abnormalities in order to understand the neuronal networks involved in relationships with others. Here we review the morphological, spectroscopic and functional abnormalities in the amygdala-hippocampal circuit, the caudate nuclei, the cerebellum, and the frontotemporal regions, which have been described in subjects with ASD. White matter abnormalities have also been described in diffusion tensor imaging, leading to suspected damage to the subjacent neural networks, such as mirror neurones or the social brain.

Influence of age on the dynamics of fMRI activations during a semantic fluency task.

PURPOSE: Age-related fMRI changes have not been extensively studied for language, whereas important adaptive mechanisms have been seen in other cognitive fields. This study examined age-related changes in fMRI activation during language tasks and, in particular, their dynamic course. PATIENTS AND METHODS: fMRI was performed on 22 young and 21 old healthy right-handed subjects during a silent category word-generation task. Activation and dynamics of BOLD signals were studied separately during the first and second portions of each 30-s block. RESULTS: Activation of the left frontal lobe was initially similar in young and old participants; however, it decreased after 30 s in the old participants. On the other hand, additional areas were initially involved only in old subjects and especially in the default mode network. CONCLUSION: This study showed age-related differences in the dynamics of fMRI activation during a silent word-generation task, suggesting a different pattern of language function with aging.

Acquisition and interactive 3D exploration of the internal structure of a dissected specimen.

We present a system to keep track of a destructive process such as a medical specimen dissection, from data acquisition to interactive and immersive visualization, in order to build ground truth models. Acquisition is a two-step process, first involving a 3D laser scanner to get a 3D surface, and then a high resolution camera for capturing the texture. This acquisition process is repeated at each step of the dissection, depending on the expected accuracy and the specific objects to be studied. Thanks to fiducial markers, surfaces are registered on each others. Experts can then explore data using interaction hardware in an immersive 3D visualization. An interactive labeling tool is provided to the anatomist, in order to identify regions of interest on each acquired surface. 3D objects can then be reconstructed according to the selected surfaces. We aim to produce ground truths which for instance can be used to validate data acquired with MRI. The system is applied to the specific case of white fibers reconstruction in the human brain.

Unique structure and optics of the lesser eyes of the box jellyfish Tripedalia cystophora.

The visual system of box jellyfish comprises a total of 24 eyes. These are of four types and each probably has a special function. To investigate this hypothesis the morphology and optics of the lesser eyes, the pit and slit eyes, were examined. The pit eyes hold one cell type only and are probably mere light meters. The slit eyes, comprising four cell types, are complex and highly asymmetric. They also hold a lens-like structure, but its optical power is minute. Optical modeling suggests spatial resolution, but only in one plane. These unique and intriguing traits support strong peripheral filtering.

Current dynamics during disruptions in large tokamaks.

Self-consistent modeling of the evolution of the plasma current during disruptions in large tokamaks is presented, taking into account both the generation of runaway electrons and their backreaction on the electric field. It is found that the current profile changes dramatically, so that the postdisruption current carried by runaway electrons is much more peaked than the thermal predisruption current. Although only a fraction of the thermal current is converted into runaway electrons, the central current density increases significantly for typical parameters in JET and ITER. It is also shown that the radial runaway profile can easily become filamented in the radial direction.

Budesonide/formoterol in a single inhaler (Symbicort) reduces healthcare costs compared with separate inhalers in the treatment of asthma over 12 months.

This open, multinational, randomised, parallel-group, six-month extension conducted in the Swedish centres of a previous six-month study compared the costs of a total of 12 months of treatment with budesonide/formoterol in a single inhaler with budesonide plus formoterol separate inhalers in 320 adults with asthma. Patients received budesonide/formoterol (Symbicort Turbuhaler) 160/4.5 mg delivered doses, two inhalations b.i.d., or corresponding doses of budesonide (Pulmicort Turbuhaler) plus formoterol (Oxis Turbuhaler). Direct costs and indirect costs were estimated. Budesonide/formoterol treatment was associated with reduced healthcare service utilisation and statistically significant reductions in direct (SEK1595, p=0.0004) and total costs (SEK1884, p=0.043) per person per year compared with budesonide plus formoterol. Budesonide/formoterol reduced the average annual emergency room admission cost per person by SEK489.7 (31% of direct cost reduction) and physician costs by SEK235.4 (15%).The direct cost of study, relief and other medication was reduced by SEK893.8 (47% of total reduction). There were no statistically significant differences in efficacy and safety parameters following treatment with budesonide/formoterol from single or separate inhalers, other than a significantly lower proportion of withdrawals with the single inhaler (9.2% vs 19.4%, p=0.008). In summary, budesonide/formoterol treatment from a single inhaler reduced 12-month treatment costs compared with separate inhalers, while maintaining at least as good control of asthma.

The costs of exacerbations in chronic obstructive pulmonary disease (COPD).

Exacerbations are the key drivers in the costs of chronic obstructive pulmonary disease (COPD). The objective was to examine the costs of COPD exacerbations in relation to differing degrees of severity of exacerbations and of COPD. We identified 202 subjects with COPD, defined according to the BTS and ERS criteria. Exacerbations were divided into mild (self-managed), mild/moderate (telephone contact with a health-care centre and/or the use of antibiotics/systemic corticosteroids), moderate (health-care centre visits) and severe (emergency care visit or hospital admission). Exacerbations were identified by sending the subjects a letter inquiring whether they had any additional respiratory problems or influenza the previous winter. At least one exacerbation was reported by 61 subjects, who were then interviewed about resource use for these events. The average health-care costs per exacerbation were SEK 120 (95% C=39-246), SEK 354 (252-475), SEK 2111 (1673-2612) and SEK 21852 (14436-29825) for mild, mild/moderate, moderate and severe exacerbations, respectively. Subjects with impaired lung function experienced more severe exacerbations, which was also reflected in the cost of exacerbations per severity of the disease during the 4 1/2 month study period (ranging from SEK 224 for mild to SEK 13708 for severe cases, median SEK 940). Exacerbations account for 35-45% of the total per capita health-care costs for COPD. In conclusion, costs varied considerably with the severity of the exacerbation as well as with the severity of COPD. The prevention of moderate-to-severe exacerbations could be very cost-effective and improve the quality of life.

The cost-effectiveness of ramipril in the treatment of patients at high risk of cardiovascular events: a Swedish sub-study to the HOPE study.

OBJECTIVE: To evaluate if long-term treatment with ramipril is cost-effective in patients at high risk of cardiovascular events. DESIGN: Randomized double-blind and placebo controlled. Information was gathered prospectively for a number of direct medical, direct nonmedical and indirect costs. SETTING AND SUBJECT: This is a sub-study to the Heart Outcomes Prevention Evaluation (HOPE) study performed in Swedish patients. All Swedish centres (19; n= 554) were invited to take part and 18 centres agreed to do so (n=537). The patients were managed in a specialist setting with a mean follow-up period of 4.5 years. Main outcome measures. The number of life-years saved was derived from the global HOPE study (n=9297) and subsequently the estimated life expectancy of those who completed the clinical study alive was added to the calculation. Direct medical costs related to cardiovascular disease only were considered in the primary analysis, whilst all kinds of costs and costs for all kinds of diseases were included in subsequent analyses. The cost of added years of life, according to the future cost method, was included in sensitivity analyses. RESULTS: The cost per life-year gained was SEK 16 600 (Euro 1940) when direct medical costs for cardiovascular reasons only were considered and SEK 45 400 (Euro 5300) when direct medical costs for all diseases were considered. The corresponding costs when direct nonmedical and indirect cost were added to the estimate were SEK 16 100 (Euro 1880) and SEK 54 600 (Euro 6380), respectively. When the future cost method was applied, the cost per life-year gained was SEK 208 300 (Euro 24 300). CONCLUSION: Ramipril is highly cost-effective in the treatment of patients at high risk of cardiovascular events.

Approximate solutions of two-way diffusion equations.

In this paper, a general and systematic scheme is formulated for finding approximate solutions of two-way diffusion equations. This expansion scheme is valid for arbitrary mean-free path and can be carried out to any desired accuracy. Its potential is demonstrated by constructing approximate solutions for two problems concerning the kinetics of an electron beam, and the accuracy is found to be very good even when only a few terms are included in the expansion. The approximate solutions found are compared with numerical calculations and previous analytical work in the literature.

The whole story: treatment outcomes with Symbicort.

Asthma is a chronic inflammatory disorder of the airways that has a considerable socioeconomic impact. Asthma management guidelines have been introduced to help provide better long-term control of asthma. Although recommended guidelines may increase the direct medication costs, the overall direct costs of asthma may be reduced due to fewer exacerbations. In addition, indirect costs due to lost productivity and mortality are reduced and patients have an improved quality of life. Inhaled corticosteroids are first-line therapy in the treatment of persistent asthma. Against this background, we have assessed the cost-effectiveness of Symbicort (budesonide and formoterol in a single inhaler), a treatment that provides better control of asthma compared with budesonide alone. While the prescribing costs of Symbicort were found to be higher than for budesonide alone, these were partially offset by reduced costs due to fewer asthma exacerbations and a reduced need for other medications. Combined long-term therapy with budesonide and formoterol also improves patient quality of life compared with budesonide alone. Two other factors associated with asthma treatment success and cost-effectiveness are patient/physic an education and good patient adherence to prescribed therapy. The introduction of a single inhaler that is easy to use in simple treatment regimens may improve patient adherence to prescribed medication, thus resulting in improved asthma control and fewer exacerbations. Treatment with Symbicort is more cost-effective than treatment with budesonide alone.

Health economic guidelines--similarities, differences and some implications.

OBJECTIVE: To classify, summarize, and compare the health economic guidelines (HE) issued in Europe, North America, and Australia to clarify similarities and differences between them. MATERIALS AND METHODS: In a literature review HE guidelines were classified according to whether they were 1) formalized, 2) informal, or 3) guidelines for health economic methods. All the guidelines were summarized in a table format according to 15 important methodological aspects. The aspects were compared both within and between the three groups. RESULTS: A total of 25 guidelines were identified, seven formalized, eight informal, and 10 guidelines for HE methods. The levels of agreement for methodological aspects within groups were 40% to 100%, 25% to 100% and 30% to 100% for the formalized, informal, and HE guidelines, respectively. The formal guidelines were slightly more homogenous than the other groups. The between-group comparison showed that the guidelines were in agreement for about 75% of methodological aspects. Disagreement between guidelines was found in choice of perspective, resources, and costs that should be included in the analysis, and in methods of evaluating resources used. CONCLUSION: A harmonization of methodological requirements and recommendations exists both within and between the guideline groups. This review provides information concerning the core of agreements that have been reached. A number of policy implications for various parties, mainly the pharmaceutical industry, were identified.