Acceptance and timeliness of standard vaccination in children with chronic neurological deficits in north-western Switzerland

There are no special recommendations for basic vaccinations in patients with chronic neurological deficits distinct from the nationwide advocated schedule in Switzerland. Reports describing adverse neurological events possibly related to vaccinations have attracted public attention. It is unclear if patients with chronic neurological deficits are more reluctantly vaccinated compared to healthy children. We therefore investigated the acceptance of vaccinations in such patients and healthy controls in a retrospective case-control study. At the University Children's Hospital, Basel, Switzerland we investigated 100 patients with chronic neurological deficits and 200 age-matched healthy controls regarding the issue of vaccination rates and ages. The total number of administered vaccinations against diphtheria, tetanus, pertussis, polio, Haemophilus influenzae type b (Hib), mumps, measles, rubella and hepatitis B were significantly lower in patients compared to healthy controls ( P <0.01 for each of the respective vaccines). Patients had an increased risk to receive the third pertussis, diphtheria, and tetanus vaccinations (relative risks (RR) for late vaccination 1.53, 1.53, and 1.54 respectively, P <0.01 for all comparisons), the second (RR=1.60, P <0.05) and third Hib vaccinations (RR=1.52, P <0.05), and the third polio vaccination (RR=1.43, P <0.05) later than controls. Conclusion:Children with chronic neurological deficits received fewer vaccinations than healthy controls. In addition, patients received vaccinations later than healthy children. Hence, it may be assumed that children with chronic neurological deficits are at an increased risk to acquire preventable infections. Therefore, vaccination should be promoted as part of the consultation during a routine appointment with the specialis

Training Fully Connected Neural Networks is ∃R\exists\mathbb{R}-Complete

We consider the algorithmic problem of finding the optimal weights and biases for a two-layer fully connected neural network to fit a given set of data points. This problem is known as empirical risk minimization in the machine learning community. We show that the problem is $\exists\mathbb{R}$-complete. This complexity class can be defined as the set of algorithmic problems that are polynomial-time equivalent to finding real roots of a polynomial with integer coefficients. Our results hold even if the following restrictions are all added simultaneously. $\bullet$ There are exactly two output neurons. $\bullet$ There are exactly two input neurons. $\bullet$ The data has only 13 different labels. $\bullet$ The number of hidden neurons is a constant fraction of the number of data points. $\bullet$ The target training error is zero. $\bullet$ The ReLU activation function is used. This shows that even very simple networks are difficult to train. The result offers an explanation (though far from a complete understanding) on why only gradient descent is widely successful in training neural networks in practice. We generalize a recent result by Abrahamsen, Kleist and Miltzow [NeurIPS 2021]. This result falls into a recent line of research that tries to unveil that a series of central algorithmic problems from widely different areas of computer science and mathematics are $\exists\mathbb{R}$-complete: This includes the art gallery problem [JACM/STOC 2018], geometric packing [FOCS 2020], covering polygons with convex polygons [FOCS 2021], and continuous constraint satisfaction problems [FOCS 2021].Comment: 38 pages, 18 figure

The Complexity of Recognizing Geometric Hypergraphs

As set systems, hypergraphs are omnipresent and have various representations ranging from Euler and Venn diagrams to contact representations. In a geometric representation of a hypergraph $H=(V,E)$, each vertex $v\in V$ is associated with a point $p_v\in \mathbb{R}^d$ and each hyperedge $e\in E$ is associated with a connected set $s_e\subset \mathbb{R}^d$ such that $\{p_v\mid v\in V\}\cap s_e=\{p_v\mid v\in e\}$ for all $e\in E$. We say that a given hypergraph $H$ is representable by some (infinite) family $F$ of sets in $\mathbb{R}^d$, if there exist $P\subset \mathbb{R}^d$ and $S \subseteq F$ such that $(P,S)$ is a geometric representation of $H$. For a family F, we define RECOGNITION(F) as the problem to determine if a given hypergraph is representable by F. It is known that the RECOGNITION problem is $\exists\mathbb{R}$-hard for halfspaces in $\mathbb{R}^d$. We study the families of translates of balls and ellipsoids in $\mathbb{R}^d$, as well as of other convex sets, and show that their RECOGNITION problems are also $\exists\mathbb{R}$-complete. This means that these recognition problems are equivalent to deciding whether a multivariate system of polynomial equations with integer coefficients has a real solution.Comment: Appears in the Proceedings of the 31st International Symposium on Graph Drawing and Network Visualization (GD 2023) 17 pages, 11 figure

PREDICTING PARTICIPATION IN AND SUCCESS OF A CONCURRENT SMOKING CESSATION PROGRAM DURING INPATIENT TREATMENT FOR ALCOHOL DEPENDENCE

Background: Predicting participation in and success of smoking cessation programs in alcohol dependent patients has yielded heterogeneous results. Moreover, these findings have rarely been based on prospective studies from clinical routine settings. Identifying predictors in prospective studies could help to tailor interventions that increase participation and success rates of smoking cessation therapies for these patients at a high risk for alcohol- and smoking-related morbidities and mortalities. Subjects and methods: During inpatient alcohol dependence treatment, 99 nicotine dependent patients were recruited. 73 patients chose to participate in a voluntary smoking cessation program. Interviews and questionnaires were used at baseline and at discharge to assess a large set of variables covering smoking and alcohol related factors, general psychopathology, quality of life and personality traits. Multiple logistic regression models were calculated to predict participation in the smoking cessation program and smoking abstinence at follow-up three months after discharge. Results: Participation in the smoking cessation program was predicted by higher stage of change, higher confidence in abstaining from smoking and lower perceived stress. Successful smoking cessation at follow-up was predicted by higher expectations of negative physical feelings due to smoking and lower expectations of temptations to smoke at baseline, and by lower number of daily smoked cigarettes at discharge. Conclusion: Despite the small sample size, this prospective study gives a first indication of clinically relevant predictors of participation in and success of a smoking cessation program by exploring many previously reported predictors simultaneously. The findings and their implications for treatment allocation and optimization are discussed. Key words

Prevalence Estimates of ADHD in a Sample of Inpatients With Alcohol Dependence

Objective: ADHD is common in patients with alcohol dependence, but prevalence results are inconsistent. We investigated ADHD prevalence in a complex design to avoid over- or underdiagnosing. Method: Patients with alcohol dependence starting long-term residential treatment were included. A structured interview (Diagnostic Interview for ADHD in Adults [DIVA]) was conducted on all patients. DIVA results indicating childhood or adulthood ADHD were assessed in successive diagnostic interviews by two expert clinicians. Results: 415 of 488 patients had completed the entire diagnostic assessment. ADHD prevalence was 20.5%. DIVA results correlated moderately with experts’ diagnoses. In patients with ADHD, a higher comorbid illicit substance use was prevalent and alcohol dependence started earlier and was more severe. Conclusion: This study provides the largest sample on ADHD prevalence in alcohol dependent inpatients. Despite great efforts to avoid overestimation, we found every fifth patient to have ADHD. ADHD diagnosis should not be based solely on a structured interview but should be clinically confirmed. (J. of Att. Dis. 2020; 24(14) 2072–2083

The Complexity of Recognizing Geometric Hypergraphs

As set systems, hypergraphs are omnipresent and have various representations. In a geometric representation of a hypergraph H=(V,E), each vertex v∈V is a associated with a point pv∈Rd and each hyperedge e∈E is associated with a connected set se⊂Rd such that {pv∣v∈V}∩se={pv∣v∈e} for all e∈E. We say that a given hypergraph H is representable by some (infinite) family F of sets in Rd, if there exist P⊂Rd and S⊆F such that (P,S) is a geometric representation of H. For a family F, we define RECOGNITION(F) as the problem to determine if a given hypergraph is representable by F. It is known that the RECOGNITION problem is ER-hard for halfspaces in Rd. We study the families of balls and ellipsoids in Rd, as well as other convex sets, and show that their RECOGNITION problems are also ER-complete. This means that these recognition problems are equivalent to deciding whether a multivariate system of polynomial equations with integer coefficients has a real solution

Inducible Gene Manipulations in Brain Serotonergic Neurons of Transgenic Rats

The serotonergic (5-HT) system has been implicated in various physiological processes and neuropsychiatric disorders, but in many aspects its role in normal and pathologic brain function is still unclear. One reason for this might be the lack of appropriate animal models which can address the complexity of physiological and pathophysiological 5-HT functioning. In this respect, rats offer many advantages over mice as they have been the animal of choice for sophisticated neurophysiological and behavioral studies. However, only recently technologies for the targeted and tissue specific modification of rat genes - a prerequisite for a detailed study of the 5-HT system - have been successfully developed. Here, we describe a rat transgenic system for inducible gene manipulations in 5-HT neurons. We generated a Cre driver line consisting of a tamoxifen-inducible CreERT2 recombinase under the control of mouse Tph2 regulatory sequences. Tissue-specific serotonergic Cre recombinase expression was detected in four transgenic TPH2-CreERT2 rat founder lines. For functional analysis of Cre-mediated recombination, we used a rat Cre reporter line (CAG-loxP.EGFP), in which EGFP is expressed after Cre-mediated removal of a loxP-flanked lacZ STOP cassette. We show an in-depth characterisation of this rat Cre reporter line and demonstrate its applicability for monitoring Cre-mediated recombination in all major neuronal subpopulations of the rat brain. Upon tamoxifen induction, double transgenic TPH2-CreERT2/CAG-loxP.EGFP rats show selective and efficient EGFP expression in 5-HT neurons. Without tamoxifen administration, EGFP is only expressed in few 5-HT neurons which confirms minimal background recombination. This 5-HT neuron specific CreERT2 line allows Cre-mediated, inducible gene deletion or gene overexpression in transgenic rats which provides new opportunities to decipher the complex functions of the mammalian serotonergic system

Tetracycline Inducible Gene Manipulation in Serotonergic Neurons

The serotonergic (5-HT) neuronal system has important and diverse physiological functions throughout development and adulthood. Its dysregulation during development or later in adulthood has been implicated in many neuropsychiatric disorders. Transgenic animal models designed to study the contribution of serotonergic susceptibility genes to a pathological phenotype should ideally allow to study candidate gene overexpression or gene knockout selectively in serotonergic neurons at any desired time during life. For this purpose, conditional expression systems such as the tet-system are preferable. Here, we generated a transactivator (tTA) mouse line (TPH2-tTA) that allows temporal and spatial control of tetracycline (Ptet) controlled transgene expression as well as gene deletion in 5-HT neurons. The tTA cDNA was inserted into a 196 kb PAC containing a genomic mouse Tph2 fragment (177 kb) by homologous recombination in E. coli. For functional analysis of Ptet-controlled transgene expression, TPH2-tTA mice were crossed to a Ptet-regulated lacZ reporter line (Ptet-nLacZ). In adult double-transgenic TPH2-tTA/Ptet-nLacZ mice, TPH2-tTA founder line L62-20 showed strong serotonergic β-galactosidase expression which could be completely suppressed with doxycycline (Dox). Furthermore, Ptet-regulated gene expression could be reversibly activated or inactivated when Dox was either withdrawn or added to the system. For functional analysis of Ptet-controlled, Cre-mediated gene deletion, TPH2-tTA mice (L62-20) were crossed to double transgenic Ptet-Cre/R26R reporter mice to generate TPH2-tTA/Ptet-Cre/R26R mice. Without Dox, 5-HT specific recombination started at E12.5. With permanent Dox administration, Ptet-controlled Cre-mediated recombination was absent. Dox withdrawal either postnatally or during adulthood induced efficient recombination in serotonergic neurons of all raphe nuclei, respectively. In the enteric nervous system, recombination could not be detected. We generated a transgenic mouse tTA line (TPH2-tTA) which allows both inducible and reversible transgene expression and inducible Cre-mediated gene deletion selectively in 5-HT neurons throughout life. This will allow precise delineation of serotonergic gene functions during development and adulthood

Standard of hygiene and immune adaptation in newborn infants

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