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Numerous areas of skull base neurosurgery and interventional neuroradiology overlap. Interventional neuroradiology techniques can often be employed in combination with open skull base surgery to provide solutions to complex cerebrovascular and oncological problems. This chapter describes the indications for, and technical nuances of, combined microsurgical and endovascular treatment of cerebrovascular and skull base disease. In particular, three major disease states are discussed: intracranial aneurysms, arteriovenous malformations of the brain and dura, and skull base tumors.
Studying phenotypic and genetic characteristics of age at onset (AAO) and polarity at onset (PAO) in bipolar disorder can provide new insights into disease pathology and facilitate the development of screening tools.
To examine the genetic architecture of AAO and PAO and their association with bipolar disorder disease characteristics.
Genome-wide association studies (GWASs) and polygenic score (PGS) analyses of AAO (n = 12 977) and PAO (n = 6773) were conducted in patients with bipolar disorder from 34 cohorts and a replication sample (n = 2237). The association of onset with disease characteristics was investigated in two of these cohorts.
Earlier AAO was associated with a higher probability of psychotic symptoms, suicidality, lower educational attainment, not living together and fewer episodes. Depressive onset correlated with suicidality and manic onset correlated with delusions and manic episodes. Systematic differences in AAO between cohorts and continents of origin were observed. This was also reflected in single-nucleotide variant-based heritability estimates, with higher heritabilities for stricter onset definitions. Increased PGS for autism spectrum disorder (β = −0.34 years, s.e. = 0.08), major depression (β = −0.34 years, s.e. = 0.08), schizophrenia (β = −0.39 years, s.e. = 0.08), and educational attainment (β = −0.31 years, s.e. = 0.08) were associated with an earlier AAO. The AAO GWAS identified one significant locus, but this finding did not replicate. Neither GWAS nor PGS analyses yielded significant associations with PAO.
AAO and PAO are associated with indicators of bipolar disorder severity. Individuals with an earlier onset show an increased polygenic liability for a broad spectrum of psychiatric traits. Systematic differences in AAO across cohorts, continents and phenotype definitions introduce significant heterogeneity, affecting analyses.
Alcohol use disorder (AUD) and schizophrenia (SCZ) frequently co-occur, and large-scale genome-wide association studies (GWAS) have identified significant genetic correlations between these disorders.
We used the largest published GWAS for AUD (total cases = 77 822) and SCZ (total cases = 46 827) to identify genetic variants that influence both disorders (with either the same or opposite direction of effect) and those that are disorder specific.
We identified 55 independent genome-wide significant single nucleotide polymorphisms with the same direction of effect on AUD and SCZ, 8 with robust effects in opposite directions, and 98 with disorder-specific effects. We also found evidence for 12 genes whose pleiotropic associations with AUD and SCZ are consistent with mediation via gene expression in the prefrontal cortex. The genetic covariance between AUD and SCZ was concentrated in genomic regions functional in brain tissues (p = 0.001).
Our findings provide further evidence that SCZ shares meaningful genetic overlap with AUD.
Background:Staphylococcus aureus (S. aureus) is the second most common cause of healthcare-acquired infections in neonates. S. aureus colonization is a known risk factor for invasive disease. Aside from healthcare workers (HCWs), recent data suggest that parents are important reservoirs of S. aureus in the neonatal intensive care unit (NICU). S. aureus typically colonizes the nares, but it can also colonize other anatomic locations such as the throat. Objective: Our objectives were to identify and compare S. aureus colonization among HCWs and parents and to identify and compare different sites of S. aureus colonization. Methods: Between April 2015 and July 2016, we performed 4 point-prevalence surveys and collected nares and throat swabs from HCWs (nurses, respiratory therapists, nurse practitioners, and physicians) at a quaternary-care NICU. During an overlapping period, we screened parents of neonates in the NICU for S. aureus colonization using nares, throat, groin, and perianal cultures as a part of an ongoing randomized control trial. Cultures from both studies were collected using standardized methods. ESwabs were used to collect samples, which were inoculated into broth for enrichment and subsequently cultured onto chromogenic agar to differentiate between MSSA and MRSA. Results: The prevalence of methicillin susceptible S. aureus (MSSA) colonization was 46% (105/226) in HCWs and 28% (239/842) in parents. The prevalence of methicillin resistant S. aureus (MRSA) colonization was 2.2% (5/226) in HCWs and 2.2% (19/842) in parents. Of those who were colonized with S. aureus, 35% (79/226) of HCWs and 46.5% (160/344) of parents had nares and throat colonization while 11.5% (26/226) of HCWs and 12.2% (42/344) of parents had only throat colonization but not nares colonization. Of those who were MRSA colonized, 1.3% (3/226) of HCWs and 1.8% (15/842) of parents had a positive nares and throat culture as compared to 0.9% (2/226) of HCWs and 0.2% (2/842) of parents had only positive throat cultures. Additionally, 68% (175/257) were colonized with S. aureus at any swabbed site including nares, throat, groin, or perinanal areas. However, only 30% (77/257) of parents had only nares colonization as compared to 58.8% (151/257) had throat and nares colonization, 38.1% (98/257) had nares and groin colonization, and 37.4% (96/257) had nares and perianal colonization. Conclusions: HCWs had greater prevalence of S. aureus colonization compared to parents. As expected, the nares was the most common site of MSSA and MRSA, but a large proportion of S. aureus colonized HCWs and parents had only throat colonization. Given the prevalence of S. aureus in non-nares sites of HCWs and parents in the NICU, further studies should examine the role of non-nares carriers in the transmission of S. aureus in this population.
Disclosures: Aaron Milstone reports consultancy with Becton Dickinson.
Studies suggest that alcohol consumption and alcohol use disorders have distinct genetic backgrounds.
We examined whether polygenic risk scores (PRS) for consumption and problem subscales of the Alcohol Use Disorders Identification Test (AUDIT-C, AUDIT-P) in the UK Biobank (UKB; N = 121 630) correlate with alcohol outcomes in four independent samples: an ascertained cohort, the Collaborative Study on the Genetics of Alcoholism (COGA; N = 6850), and population-based cohorts: Avon Longitudinal Study of Parents and Children (ALSPAC; N = 5911), Generation Scotland (GS; N = 17 461), and an independent subset of UKB (N = 245 947). Regression models and survival analyses tested whether the PRS were associated with the alcohol-related outcomes.
In COGA, AUDIT-P PRS was associated with alcohol dependence, AUD symptom count, maximum drinks (R2 = 0.47–0.68%, p = 2.0 × 10−8–1.0 × 10−10), and increased likelihood of onset of alcohol dependence (hazard ratio = 1.15, p = 4.7 × 10−8); AUDIT-C PRS was not an independent predictor of any phenotype. In ALSPAC, the AUDIT-C PRS was associated with alcohol dependence (R2 = 0.96%, p = 4.8 × 10−6). In GS, AUDIT-C PRS was a better predictor of weekly alcohol use (R2 = 0.27%, p = 5.5 × 10−11), while AUDIT-P PRS was more associated with problem drinking (R2 = 0.40%, p = 9.0 × 10−7). Lastly, AUDIT-P PRS was associated with ICD-based alcohol-related disorders in the UKB subset (R2 = 0.18%, p < 2.0 × 10−16).
AUDIT-P PRS was associated with a range of alcohol-related phenotypes across population-based and ascertained cohorts, while AUDIT-C PRS showed less utility in the ascertained cohort. We show that AUDIT-P is genetically correlated with both use and misuse and demonstrate the influence of ascertainment schemes on PRS analyses.
While the role of consultants in the policy process has long been a concern for scholars of public administration, public management and political science, empirical studies of policy-related consulting are scarce, with little quantitative data. The country-level case studies in this book shed light for the first time on a number of important but as yet under-researched questions. The first is the actual extent of the use of government consulting in a number of countries, and what have been cross-time developments: to what extent has the use of consultants grown over time, and what are the (political, fiscal-economic, society, policy-related) factors that explain greater or lesser growth in a particular country or sector? The second is the question of what role(s) consultants play in the public sector and how large is the share of these consultants in policy work (policy analysis, policy advice, implementation and evaluation).
Demands made by the UK government for external policy support are big business, where the highest spend on consultants has been calculated at £2 billion in 2003–2004 (NAO 2006), and currently major consultancy firms are active in bidding for six months of Brexit work with a price tag of £1.5 million (Martin 2017). At the same time, the focus has been on review and retrenchment, with a fall in spending to £1.8b in 2005–2006 (NAO 2006), whereby ‘the government is determined to make every taxpayer penny count’ and the ‘Cabinet Office is working to help departments reduce reliance on everything from expensive consultants to print cartridges’ (Gov.uk ). Thus, it seems there is recognition of a contribution to public policy that is beyond ‘in-house’ capacity: ‘when used correctly and in the appropriate circumstances … [they] … can provide great benefit to clients – achieving things that clients do not have the capacity or capability to do themselves’ (NAO 2006: 4).
The use of external consultants by the public sector has been an increasingly relevant area of focus for almost three decades, for both government bodies (ANAO 2001; House of Commons Committee of Public Accounts (UK) 2010) and academics (Bakvis 1997; Perl and White 2002; Saint-Martin 2005; Speers 2007; Howlett, Migone and Seck 2014; Howlett and Migone 2014). This is due to both the costs and the role of private sector entities in shaping policy capacity and policy choice. Aside from the most recent contributions, the main focus has been the financial impact of contracting out this function rather than on understanding how external sources have affected the capacity of departments and other government units (Riddell 2007). There are various reasons for this trend.