Explore the vast range of titles available.

Routine rewriting of loci associated with human traits and diseases would facilitate their functional analysis. However, existing DNA integration approaches are limited in terms of scalability and portability across genomic loci and cellular contexts. We describe Big-IN, a versatile platform for targeted integration of large DNAs into mammalian cells. CRISPR/Cas9-mediated targeting of a landing pad enables subsequent recombinase-mediated delivery of variant payloads and efficient positive/negative selection for correct clones in mammalian stem cells. We demonstrate integration of constructs up to 143 kb, and an approach for one-step scarless delivery. We developed a staged pipeline combining PCR genotyping and targeted capture sequencing for economical and comprehensive verification of engineered stem cells. Our approach should enable combinatorial interrogation of genomic functional elements and systematic locus-scale analysis of genome function.

With psychopathology rising during adolescence and evidence suggesting that adult mental health burden is often due to disorders beginning in youth, it is important to investigate the epidemiology of adolescent mental disorders. We analysed data gathered at ages 11 (baseline) and 19 years from the population-based Dutch TRacking Adolescents' Individual Lives Survey (TRAILS) study. At baseline we administered the Achenbach measures (Child Behavior Checklist, Youth Self-Report) and at age 19 years the World Health Organization's Composite International Diagnostic Interview version 3.0 (CIDI 3.0) to 1584 youths. Lifetime, 12-month and 30-day prevalences of any CIDI-DSM-IV disorder were 45, 31 and 15%, respectively. Half were severe. Anxiety disorders were the most common but the least severe whereas mood and behaviour disorders were less prevalent but more severe. Disorders persisted, mostly by recurrence in mood disorders and chronicity in anxiety disorders. Median onset age varied substantially across disorders. Having one disorder increased subjects' risk of developing another disorder. We found substantial homotypic and heterotypic continuity. Baseline problems predicted the development of diagnosable disorders in adolescence. Non-intact families and low maternal education predicted externalizing disorders. Most morbidity concentrated in 5-10% of the sample, experiencing 34-55% of all severe lifetime disorders. At late adolescence, 22% of youths have experienced a severe episode and 23% only mild episodes. This psychopathology is rather persistent, mostly due to recurrence, showing both monotypic and heterotypic continuity, with family context affecting particularly externalizing disorders. High problem levels at age 11 years are modest precursors of incident adolescent disorders. The burden of mental illness concentrates in 5-10% of the adolescent population.

Indo-Pacific lionfish (Pterois volitans and P. miles) are the first marine teleost to become established in the Western Atlantic Ocean, Caribbean Sea, and Gulf of Mexico. Lionfish have been labeled a global conservation issue and pose major threats to local economies. To test whether commercial harvest of lionfish is a socially accepted management approach in Texas, we measured the components of an environmental behavior intention model with survey responses of Texas Gulf Coast residents (n = 420). Regression analyses of survey responses indicate that individuals were significantly more willing to consume lionfish if they had a high level of concern for the environmental problems posed by the invasive species and were more knowledgeable about the fish. Participation in an educational program that addresses lionfish was also found to be associated with greater willingness to consume lionfish among those who are moderately to highly concerned about the issue. The originality of this study is related to its contribution in identifying social factors that contribute to an individual’s willingness to consume lionfish. Insights from this study demonstrate the attitudinal and behavioral mechanisms that can be addressed to increase acceptance of using consumption as a sustainable management strategy to combat marine fish invasions.

Timely recognition and treatment of mental disorders with an onset in childhood and adolescence is paramount, as these are characterized by greater severity and longer persistence than disorders with an onset in adulthood. Studies examining time-to-treatment, also referred to as treatment delay, duration of untreated illness or latency to treatment, and defined as the time between disorder onset and initial treatment contact, are sparse and all based on adult samples. The aim of this study was to describe time-to-treatment and its correlates for any health care professional (any care) and secondary mental health care (secondary care), for a broad range of mental disorders, in adolescents. Data from the Dutch community-based cohort study TRacking Adolescents' Individual Lives Survey (TRAILS; N = 2230) were used. The Composite International Diagnostic Interview (CIDI) was administered to assess DSM-IV disorders, the age of onset, and the age of initial treatment contact with any health care professional in 1584 adolescents of 18-20 years old. In total 43% of the adolescents (n = 675) were diagnosed with a lifetime DSM-IV disorder. The age of initial treatment contact with secondary care was based on administrative records from 321 adolescents without a disorder onset before the age of 10. Descriptive statistics, cumulative lifetime probability plots, and Cox regression analyses were used analyze time-to-treatment. The proportion of adolescents who reported lifetime treatment contact with any care varied from 15% for alcohol dependence to 82% for dysthymia. Regarding secondary care, proportions of lifetime treatment contact were lower for mood disorders and higher for substance dependence. Time-to-treatment for any care varied considerably between and within diagnostic classes. The probability of lifetime treatment contact for mood disorders was above 90%, whereas for other mental disorders this was substantially lower. An earlier age of onset predicted a longer, and the presence of a co-morbid mood disorder predicted a shorter time-to-treatment in general. Disorder severity predicted a shorter time-to-treatment for any care, but not for secondary care. Time-to-treatment for secondary care was shorter for adolescents from low and middle socioeconomic background than for adolescents from a high socioeconomic background. Although the time-to-treatment was shorter for adolescents than for adults, it was still substantial, and the overall patterns were remarkably similar to those found in adults. Efforts to reduce time-to-treatment should therefore be aimed at children and adolescents. Future research should address mechanisms underlying time-to-treatment and its consequences for early-onset disorders in particular.

Various sources indicate that mental disorders are the leading contributor to the burden of disease among youth. An important determinant of functioning is current mental health status. This study investigated whether psychiatric history has additional predictive power when predicting individual differences in functional outcomes. We used data from the Dutch TRAILS study in which 1778 youths were followed from pre-adolescence into young adulthood (retention 80%). Of those, 1584 youths were successfully interviewed, at age 19, using the World Health Organization Composite International Diagnostic Interview (CIDI 3.0) to assess current and past CIDI-DSM-IV mental disorders. Four outcome domains were assessed at the same time: economic (e.g. academic achievement, social benefits, financial difficulties), social (early motherhood, interpersonal conflicts, antisocial behavior), psychological (e.g. suicidality, subjective well-being, loneliness), and health behavior (e.g. smoking, problematic alcohol, cannabis use). Out of the 19 outcomes, 14 were predicted by both current and past disorders, three only by past disorders (receiving social benefits, psychiatric hospitalization, adolescent motherhood), and two only by current disorder (absenteeism, obesity). Which type of disorders was most important depended on the outcome. Adjusted for current disorder, past internalizing disorders predicted in particular psychological outcomes while externalizing disorders predicted in particular health behavior outcomes. Economic and social outcomes were predicted by a history of co-morbidity of internalizing and externalizing disorder. The risk of problematic cannabis use and alcohol consumption dropped with a history of internalizing disorder. To understand current functioning, it is necessary to examine both current and past psychiatric status.

High Island A-389-A (HI-A-389-A) is a gas platform situated in 125 m water within Flower Garden Banks National Marine Sanctuary in the northwestern Gulf of Mexico, and provides habitat to a diverse array of benthic organisms and fish species. Platform production ceased in 2012, beginning the decommissioning process for structural removal. Rather than complete removal of the structure, the lower portion was left intact as an artificial reef and the upper 21 m was removed. The biological communities (benthic and fish) were characterized during diver and remotely operated vehicle surveys, both before and after removal of the upper structure. The platform’s benthic community, primarily categorized as fouling organisms, was mainly composed of sponges, hydroids, macroalgae, bivalves, zoanthids, and stony corals. The dominant stony coral was orange cup coral (Tubastraea sp.), an exotic species, while native coral species were rare. Fish species were predominantly demersal planktivores. Analyses of the benthic and fish communities documented four distinct biological zones strongly associated with depth. Significant differences in the benthic community were observed after partial removal and varied with depth, including the loss of hydroids, increase in macroalgae cover, and sponge and coral community changes. Both demersal and pelagic fish communities exhibited significant differences by depth after removal but no significant changes were observed in federally managed species. Results reflect changes in benthic and fish communities after partial removal of the platform that is likely, in part, influenced by structure removal and temporal variations.

East Flower Garden Bank (EFGB) and West Flower Garden Bank (WFGB), part of Flower Garden Banks National Marine Sanctuary (FGBNMS) in the northwestern Gulf of Mexico, support tropical coral reefs that exhibit over 50% living coral cover. These reefs have been monitored annually since 1989, and in 2016 were exposed to higher than normal seawater temperatures leading to a severe bleaching event. Corals at EFGB and WFGB showed no signs of bleaching until September 2016, occurring later in the year compared to other reefs in the Caribbean region. Coral bleaching and subsequent recovery at each bank were documented through a time series of repetitive photographs within previously established long-term monitoring stations. Preceding the event, mean live coral cover within monitoring stations was collectively 64 ± 2%. Prior to signs of bleaching from July to September 2016, seawater temperatures on the reef were above 30 °C for a total of 36 d at EFGB and 21 d at WFGB. By October 2016, 67 ± 5% of the coral cover within EFGB monitoring stations and 25 ± 3% within WFGB monitoring stations exhibited signs of bleaching or paling stress, with dissimilarities in the amount of bleaching most likely due to significant differences in thermal profiles between banks. Significantly increasing long-term trends for daily mean seawater temperature indicate that temperatures on the banks have become warmer over time, and calculated bleaching threshold curves suggest that more than 50 d above 29.5 °C would initiate a bleaching year at EFGB and WFGB. Even though recovery within monitoring stations at both banks was documented with no significant declines in mean coral cover from 2016 to 2017 (64% and 62%, respectively), it is likely FGBNMS will be subject to additional and more frequent bleaching events in the future as ocean temperatures continue to rise.

Background: The anatomical nature of the ureteroscopic approach for biopsy of upper urothelial tract tumors requires the utilization of small instruments, often limiting biopsy specimen quality. This leads to lower-than-desired tumor grading accuracy and malignancy detection capabilities on the initial evaluation of upper tract tumor specimens. This is problematic because optimal treatment of upper tract urothelial carcinoma (UTUC) depends on early disease detection and subsequent accurate diagnosis. Objective: The objective of our study was to compare the biopsy capabilities of two ureteroscopic biopsy instruments - biopsy forceps and the nitinol stone retrieval basket. Methods: We performed a retrospective analysis of ten patients who underwent biopsy of an upper tract mass with either instrument. Average specimen size, muscularis propria presence, and malignancy detection sensitivity were the variables of interest. Results: The nitinol stone retrieval basket obtained larger biopsy samples than the biopsy forceps, with average biopsy volumes being 0.0674 cm3 and 0.0075 cm3, respectively (P = 0.00017); this was the only statistically significant result of our study. Muscularis propria was present in 31% (4/13) of the biopsies with the nitinol stone retrieval basket, whereas 0% (0/5) of the biopsy forceps biopsies contained muscularis propria (P = 0.2778). Regarding malignancy detection sensitivity, the nitinol stone retrieval basket biopsies identified malignancy in 100% of the specimens that had confirmed malignancy; the biopsy forceps only detected malignancy 40% of the time (P = 0.4134). Conclusion: These findings suggest that the nitinol stone retrieval basket is a useful diagnostic tool for UTUC, although further investigation is warranted to determine its superiority compared to biopsy forceps.

Evidence is required to quantify the potential risks of transmission of variant Creutzfeldt Jakob (vCJD) through dental procedures. Studies, using animal models relevant to vCJD, were performed to address two questions. Firstly, whether oral tissues could become infectious following dietary exposure to BSE? Secondly, would a vCJD-contaminated dental instrument be able to transmit disease to another patient? BSE-301V was used as a clinically relevant model for vCJD. VM-mice were challenged by injection of infected brain homogenate into the small intestine (Q1) or by five minute contact between a deliberately-contaminated dental file and the gingival margin (Q2). Ten tissues were collected from groups of challenged mice at three or four weekly intervals, respectively. Each tissue was pooled, homogenised and bioassayed in indicator mice. Challenge via the small intestine gave a transmission rate of 100% (mean incubation 157±17 days). Infectivity was found in both dental pulp and the gingival margin within 3 weeks of challenge and was observed in all tissues tested within the oral cavity before the appearance of clinical symptoms. Following exposure to deliberately contaminated dental files, 97% of mice developed clinical disease (mean incubation 234±33 days). Infectivity was higher than expected, in a wider range of oral tissues, than was allowed for in previous risk assessments. Disease was transmitted following transient exposure of the gingiva to a contaminated dental file. These observations provide evidence that dental procedures could be a route of cross-infection for vCJD and support the enforcement of single-use for certain dental instruments.