Lack of guidelines and translational knowledge is hindering the implementation of psychiatric genetic counseling and testing within Europe - A multi-professional survey study

Genetic research has identified a large number of genetic variants, both rare and common, underlying neurodevelopmental disorders (NDD) and major psychiatric disorders. Currently, these findings are being translated into clinical practice. However, there is a lack of knowledge and guidelines for psychiatric genetic testing (PsychGT) and genetic counseling (PsychGC). The European Union-funded COST action EnGagE (CA17130) network was started to investigate the current implementation status of PsychGT and PsychGC across 35 participating European countries. Here, we present the results of a pan-European online survey in which we gathered the opinions, knowledge, and practices of a self-selected sample of professionals involved/interested in the field. We received answers from 181 respondents. The three main occupational categories were genetic counselor (21.0%), clinical geneticist (24.9%), and researcher (25.4%). Of all 181 respondents, 106 provide GC for any psychiatric disorder or NDD, corresponding to 58.6% of the whole group ranging from 43.2% in Central Eastern Europe to 66.1% in Western Europe. Overall, 65.2% of the respondents reported that genetic testing is offered to individuals with NDD, and 26.5% indicated the same for individuals with major psychiatric disorders. Only 22.1% of the respondents indicated that they have guidelines for PsychGT. Pharmacogenetic testing actionable for psychiatric disorders was offered by 15%. Interestingly, when genetic tests are fully covered by national health insurance, more genetic testing is provided for individuals with NDD but not those with major psychiatric disorders. Our qualitative analyses of responses highlight the lack of guidelines and knowledge on utilizing and using genetic tests and education and training as the major obstacles to implementation. Indeed, the existence of psychiatric genetic training courses was confirmed by only 11.6% of respondents. The question on the relevance of up-to-date education and training in psychiatric genetics on everyday related practice was highly relevant. We provide evidence that PsychGC and PsychGT are already in use across European countries, but there is a lack of guidelines and education. Harmonization of practice and development of guidelines for genetic counseling, testing, and training professionals would improve equality and access to quality care for individuals with psychiatric disorders within Europe

Rectangles are nonnegative juntas

We develop a new method to prove communication lower bounds for composed functions of the form fgn where f is any boolean function on n inputs and g is a sufficiently hard two-party gadget. Our main structure theorem states that each rectangle in the communication matrix of fgn can be simulated by a nonnegative combination of juntas. This is the strongest yet formalization for the intuition that each low-communication randomized protocol can only query few inputs of f as encoded by the gadget g. Consequently, we characterize the communication complexity of f o gn in all known one-sided zero-communication models by a corresponding query complexity measure of f. These models in turn capture important lower bound techniques such as corruption, smooth rectangle bound, relaxed partition bound, and extended discrepancy. As applications, we resolve several open problems from prior work: We show that SBPcc (a class characterized by corruption) is not closed under intersection. An immediate corollary is that MAcc ≠ SBPcc. These results answer questions of Klauck (CCC 2003) and Böhler et al. (JCSS 2006). We also show that approximate nonnegative rank of partial boolean matrices does not admit efficient error reduction. This answers a question of Kol et al. (ICALP 2014) for partial matrices

Rectangles are nonnegative juntas

We develop a new method to prove communication lower bounds for composed functions of the form fogn, where f is any boolean function on n inputs and g is a sufficiently hard two-party gadget. Our main structure theorem states that each rectangle in the communication matrix of fogn can be simulated by a nonnegative combination of juntas. This is a new formalization for the intuition that each low-communication randomized protocol can only query a few inputs of f as encoded by the gadget g. Consequently, we characterize the communication complexity of fogn in all known one-sided (i.e., not closed under complement) zero-communication models by a corresponding query complexity measure of f. These models in turn capture important lower bound techniques such as corruption, smooth rectangle bound, relaxed partition bound, and extended discrepancy. As applications, we resolve several open problems from prior work. We show that SBPcc (a class characterized by corruption) is not closed under intersection. An immediate corollary is that MAcc ≠= SBPcc. These results answer questions of Klauck [Proceedings of the 18th Conference on Computational Complexity (CCC), IEEE Computer Society, Los Alamitos, CA, 2003, pp. 118-134] and Böhler, Glasser, and Meister [J. Comput. System Sci., 72 (2006), pp. 1043-1076]. We also show that the approximate nonnegative rank of partial boolean matrices does not admit efficient error reduction. This answers a question of Kol et al. [Proceedings of the 41st International Colloquium on Automata, Languages, and Programming (ICALP), Springer, Berlin, 2014, pp. 701-712] for partial matrices. In subsequent work, our structure theorem has been applied to resolve the communication complexity of the clique versus independent set problem

Rectangles are nonnegative juntas

We develop a new method to prove communication lower bounds for composed functions of the form fogn, where f is any boolean function on n inputs and g is a sufficiently hard two-party gadget. Our main structure theorem states that each rectangle in the communication matrix of fogn can be simulated by a nonnegative combination of juntas. This is a new formalization for the intuition that each low-communication randomized protocol can only query a few inputs of f as encoded by the gadget g. Consequently, we characterize the communication complexity of fogn in all known one-sided (i.e., not closed under complement) zero-communication models by a corresponding query complexity measure of f. These models in turn capture important lower bound techniques such as corruption, smooth rectangle bound, relaxed partition bound, and extended discrepancy. As applications, we resolve several open problems from prior work. We show that SBPcc (a class characterized by corruption) is not closed under intersection. An immediate corollary is that MAcc ≠= SBPcc. These results answer questions of Klauck [Proceedings of the 18th Conference on Computational Complexity (CCC), IEEE Computer Society, Los Alamitos, CA, 2003, pp. 118-134] and Böhler, Glasser, and Meister [J. Comput. System Sci., 72 (2006), pp. 1043-1076]. We also show that the approximate nonnegative rank of partial boolean matrices does not admit efficient error reduction. This answers a question of Kol et al. [Proceedings of the 41st International Colloquium on Automata, Languages, and Programming (ICALP), Springer, Berlin, 2014, pp. 701-712] for partial matrices. In subsequent work, our structure theorem has been applied to resolve the communication complexity of the clique versus independent set problem

Epidemiology and Transmitted HIV-1 Drug Resistance among Treatment-Naïve Individuals in Israel, 2010–2018

Despite the low prevalence of HIV-1 in Israel, continuous waves of immigration may have impacted the local epidemic. We characterized all people diagnosed with HIV-1 in Israel in 2010–2018. The demographics and clinical data of all individuals (n = 3639) newly diagnosed with HIV-1 were retrieved. Subtypes, transmitted drug-resistance mutations (TDRM), and phylogenetic relations, were determined in >50% of them. In 39.1%, HIV-1 transmission was through heterosexual contact; 34.3% were men who have sex with men (MSM); and 10.4% were people who inject drugs. Many (>65%) were immigrants. Israeli-born individuals were mostly (78.3%) MSM, whereas only 9% of those born in Sub-Saharan Africa (SSA), Eastern Europe and Central Asia (EEU/CA), were MSM. The proportion of individuals from SSA decreased through the years 2010–2018 (21.1% in 2010–2012; 16.8% in 2016–2018) whereas those from EEU/CA increased significantly (21% in 2010–2012; 27.8% in 2016–2018, p < 0.001). TDRM were identified in 12.1%; 3.7, 3.3 and 6.6% had protease inhibitors (PI), nucleotide reverse transcriptase inhibitors (NRTI), and non-nucleoside reverse transcriptase inhibitors (NNRTI) TDRM, respectively, with the overall proportion remaining stable in the studied years. None had integrase TDRM. Subtype B was present in 43.9%, subtype A in 25.2% (A6 in 22.8 and A1 in 2.4%) and subtype C in 17.1% of individuals. Most MSM had subtype B. Subtype C carriers formed small clusters (with one unexpected MSM cluster), A1 formed a cluster mainly of locally-born patients with NNRTI mutations, and A6 formed a looser cluster of individuals mainly from EEU. Israelis, <50 years old, carrying A1, had the highest risk for having TDRM. In conclusion, an increase in immigrants from EEU/CA and a decrease in those from SSA characterized the HIV-1 epidemic in 2010–2018. Baseline resistance testing should still be recommended to identify TDRM, and improve surveillance and care