Participant Perceptions of Facilitators and Barriers to Adherence in a Digital Mental Health Intervention for a Nonclinical Cohort: Content Analysis.

BACKGROUND: Digital mental health promotion interventions (MHPIs) present a scalable opportunity to attenuate the risk of mental health distress among nonclinical cohorts. However, adherence is frequently suboptimal, and little is known about participants' perspectives concerning facilitators and barriers to adherence in community-based settings. OBJECTIVE: This study aimed to examine participants' perceptions of facilitators and barriers to adherence in a web- and mobile app-based MHPI for a nonclinical cohort. METHODS: This qualitative study used inductive, reflexive thematic analysis to explore free-text responses in a postintervention evaluation of a 10-week digital MHPI. The intervention was administered using a web and mobile app from September to December 2018. Participants (N=320) were Australian and New Zealand members of a faith-based organization who self-selected into the study, owned a mobile phone with messaging capability, had an email address and internet access, were fluent in English, provided informed consent, and gave permission for their data to be used for research. The postintervention questionnaire elicited participants' perceptions of facilitators and barriers to adherence during the intervention period. RESULTS: Key factors that facilitated adherence were engaging content, time availability and management, ease of accessibility, easy or enjoyable practical challenges, high perceived value, and personal motivation to complete the intervention. The primary perceived barrier to adherence was the participants' lack of time. Other barriers included completing and recording practical activities, length of video content, technical difficulties, and a combination of personal factors. CONCLUSIONS: Time scarcity was the foremost issue for the nonclinical cohort engaged in this digital MHPI. Program developers should streamline digital interventions to minimize the time investment for participants. This may include condensed content, optimization of intuitive web and app design, simplified recording of activities, and greater participant autonomy in choosing optional features. Nonetheless, participants identified a multiplicity of other interindividual factors that facilitated or inhibited adherence.

The Influence of Three Modes of Human Support on Attrition and Adherence to a Web- and Mobile App-Based Mental Health Promotion Intervention in a Nonclinical Cohort: Randomized Comparative Study.

BACKGROUND: The escalating prevalence of mental health disorders necessitates a greater focus on web- and mobile app-based mental health promotion initiatives for nonclinical groups. However, knowledge is scant regarding the influence of human support on attrition and adherence and participant preferences for support in nonclinical settings. OBJECTIVE: This study aimed to compare the influence of 3 modes of human support on attrition and adherence to a digital mental health intervention for a nonclinical cohort. It evaluated user preferences for support and assessed whether adherence and outcomes were enhanced when participants received their preferred support mode. METHODS: Subjects participated in a 10-week digital mental health promotion intervention and were randomized into 3 comparative groups: standard group with automated emails (S), standard plus personalized SMS (S+pSMS), and standard plus weekly videoconferencing support (S+VCS). Adherence was measured by the number of video lessons viewed, points achieved for weekly experiential challenge activities, and the total number of weeks that participants recorded a score for challenges. In the postquestionnaire, participants ranked their preferred human support mode from 1 to 4 (S, S+pSMS, S+VCS, S+pSMS & VCS combined). Stratified analysis was conducted for those who received their first preference. Preintervention and postintervention questionnaires assessed well-being measures (ie, mental health, vitality, depression, anxiety, stress, life satisfaction, and flourishing). RESULTS: Interested individuals (N=605) enrolled on a website and were randomized into 3 groups (S, n=201; S+pSMS, n=202; S+VCS, n=201). Prior to completing the prequestionnaire, a total of 24.3% (147/605) dropped out. Dropout attrition between groups was significantly different (P=.009): 21.9% (44/201) withdrew from the S group, 19.3% (39/202) from the S+pSMS group, and 31.6% (64/202) from the S+VCS group. The remaining 75.7% (458/605) registered and completed the prequestionnaire (S, n=157; S+pSMS, n=163; S+VCS, n=138). Of the registered participants, 30.1% (138/458) failed to complete the postquestionnaire (S, n=54; S+pSMS, n=49; S+VCS, n=35), but there were no between-group differences (P=.24). For the 69.9% (320/458; S, n=103; S+pSMS, n=114; S+VCS, n=103) who completed the postquestionnaire, no between-group differences in adherence were observed for mean number of videos watched (P=.42); mean challenge scores recorded (P=.71); or the number of weeks that challenge scores were logged (P=.66). A total of 56 participants (17.5%, 56/320) received their first preference in human support (S, n=22; S+pSMS, n=26; S+VCS, n=8). No differences were observed between those who received their first preference and those who did not with regard to video adherence (P=.91); challenge score adherence (P=.27); or any of the well-being measures including, mental health (P=.86), vitality (P=.98), depression (P=.09), anxiety (P=.64), stress (P=.55), life satisfaction (P=.50), and flourishing (P=.47). CONCLUSIONS: Early dropout attrition may have been influenced by dissatisfaction with the allocated support mode. Human support mode did not impact adherence to the intervention, and receiving the preferred support style did not result in greater adherence or better outcomes. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry (ANZCTR): 12619001009101; http://www.anzctr.org.au/ACTRN12619001009101.aspx.

A Web- and Mobile App-Based Mental Health Promotion Intervention Comparing Email, Short Message Service, and Videoconferencing Support for a Healthy Cohort: Randomized Comparative Study.

BACKGROUND: The rapid increase in mental health disorders has prompted a call for greater focus on mental health promotion and primary prevention. Web- and mobile app-based interventions present a scalable opportunity. Little is known about the influence of human support on the outcomes of these interventions. OBJECTIVE: This study aimed to compare the influence of 3 modes of human support on the outcomes (ie, mental health, vitality, depression, anxiety, stress, life satisfaction, and flourishing) of a 10-week, Web- and mobile app-based, lifestyle-focused mental health promotion intervention among a healthy adult cohort. METHODS: Participants were recruited voluntarily using a combination of online and offline advertising. They were randomized, unblinded into 3 groups differentiated by human support mode: Group 1 (n=201): standard-fully automated emails (S); Group 2 (n=202): standard plus personalized SMS (S+pSMS); and Group 3 (n=202): standard plus weekly videoconferencing support (S+VCS), hosted by 1 trained facilitator. Participants accessed the intervention, including the questionnaire, on a Web-based learning management system or through a mobile app. The questionnaire, administered at pre- and postintervention, contained self-reported measures of mental well-being, including the "mental health" and "vitality" subscales from the Short Form Health Survey-36, Depression Anxiety and Stress Scale-21, Diener Satisfaction With Life Scale (SWLS), and Diener Flourishing Scale. RESULTS: Of 605 potential participants, 458 (S: n=157, S+pSMS: n=163, and S+VCS: n=138) entered the study by completing registration and the preintervention questionnaire. At post intervention, 320 out of 458 participants (69.9%; S: n=103, S+pSMS: n=114, and S+VCS: n=103) completed the questionnaire. Significant within-group improvements were recorded from pre- to postintervention in all groups and in every outcome measure (P≤.001). No significant between-group differences were observed for outcomes in any measure: mental health (P=.77), vitality (P=.65), depression (P=.93), anxiety (P=.25), stress (P.57), SWLS (P=.65), and Flourishing Scale (P=.99). Adherence was not significantly different between groups for mean videos watched (P=.42) and practical activity engagement (P=.71). Participation in videoconference support sessions (VCSSs) was low; 37 out of 103 (35.9%) participants did not attend any VCSSs, and only 19 out of 103 (18.4%) attended 7 or more out of 10 sessions. Stratification within the S+VCS group revealed that those who attended 7 or more VCSSs experienced significantly greater improvements in the domains of mental health (P=.006; d=0.71), vitality (P=.005; d=0.73), depression (P=.04; d=0.54), and life satisfaction (P=.046; d=0.50) compared with participants who attended less than 7. CONCLUSIONS: A Web- and mobile app-based mental health promotion intervention enhanced domains of mental well-being among a healthy cohort, irrespective of human support. Low attendance at VCSSs hindered the ability to make meaningful between-group comparisons. Supplementing the intervention with VCSSs might improve outcomes when attendance is optimized. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry (ANZCTR): 12619001009101; http://www.anzctr.org.au/ACTRN12619001009101.aspx.

Zinc-finger directed double-strand breaks within CAG repeat tracts promote repeat instability in human cells.

Expanded triplet repeats have been identified as the genetic basis for a growing number of neurological and skeletal disorders. To examine the contribution of double-strand break repair to CAG x CTG repeat instability in mammalian systems, we developed zinc finger nucleases (ZFNs) that recognize and cleave CAG repeat sequences. Engineered ZFNs use a tandem array of zinc fingers, fused to the FokI DNA cleavage domain, to direct double-strand breaks (DSBs) in a site-specific manner. We first determined that the ZFNs cleave CAG repeats in vitro. Then, using our previously described tissue culture assay for identifying modifiers of CAG repeat instability, we found that transfection of ZFN-expression vectors induced up to a 15-fold increase in changes to the CAG repeat in human and rodent cell lines, and that longer repeats were much more sensitive to cleavage than shorter ones. Analysis of individual colonies arising after treatment revealed a spectrum of events consistent with ZFN-induced DSBs and dominated by repeat contractions. We also found that expressing a dominant-negative form of RAD51 in combination with a ZFN, dramatically reduced the effect of the nuclease, suggesting that DSB-induced repeat instability is mediated, in part, through homology directed repair. These studies identify a ZFN as a useful reagent for characterizing the effects of DSBs on CAG repeats in cells.

The Influence of Gender and Age on the Outcomes of and Adherence to a Digital Interdisciplinary Mental Health Promotion Intervention in an Australasian Nonclinical Setting: Cohort Study.

BACKGROUND: The global prevalence of mental health disorders is at a crisis point, particularly in the wake of COVID-19, prompting calls for the development of digital interdisciplinary mental health promotion interventions (MHPIs) for nonclinical cohorts. However, the influence of gender and age on the outcomes of and adherence to MHPIs is not well understood. OBJECTIVE: The aim of this study was to determine the influence of gender and age on the outcomes of and adherence to a 10-week digital interdisciplinary MHPI that integrates strategies from positive psychology and lifestyle medicine and utilizes persuasive systems design (PSD) principles in a nonclinical setting. METHODS: This study involved 488 participants who completed the digital interdisciplinary MHPI. Participants completed a pre and postintervention questionnaire that used: (1) the "mental health" and "vitality" subscales from the Short Form 36 (SF-36) Health Survey; (2) the Depression, Anxiety and Stress Scale (DASS-21); and (3) Satisfaction With Life Scale (SWL). Adherence to the digital interdisciplinary MHPI was measured by the number of educational videos the participants viewed and the extent to which they engaged in experiential challenge activities offered as part of the program. RESULTS: On average, the participants (N=488; mean age 47.1 years, SD 14.1; 77.5% women) demonstrated statistically significant improvements in all mental health and well-being outcome measures, and a significant gender and age interaction was observed. Women tended to experience greater improvements than men in the mental health and well-being measures, and older men experienced greater improvements than younger men in the mental health and vitality subscales. Multiple analysis of variance results of the adherence measures indicated a significant difference for age but not gender. No statistically significant interaction between gender and age was observed for adherence measures. CONCLUSIONS: Digital interdisciplinary MHPIs that utilize PSD principles can improve the mental health and well-being of nonclinical cohorts, regardless of gender or age. Hence, there may be a benefit in utilizing PSD principles to develop universal MHPIs such as that employed in this study, which can be used across gender and age groups. Future research should examine which PSD principles optimize universal digital interdisciplinary MHPIs. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry ACTRN12619000993190; http://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=377889 and Australian New Zealand Clinical Trials Registry ACTRN12619001009101; http://www.anzctr.org.au/ACTRN12619001009101.aspx.

The Influence of Human Support on the Effectiveness of Digital Mental Health Promotion Interventions for the General Population.

Mental wellbeing amongst the general population is languishing-exacerbated by the Coronavirus Disease 2019 (COVID-19) pandemic. Digital mental health promotion interventions, that improve mental health literacy and encourage adoption of evidence-informed practical strategies are essential. However, attrition and non-adherence are problematic in digital interventions. Human support is often applied as an antidote; yet, there is a paucity of randomized trials that compare different human support conditions amongst general population cohorts. Limited trials generally indicate that human support has little influence on adherence or outcomes in DMHPIs. However, providing participants autonomy to self-select automated support options may enhance motivation and adherence.

The effectiveness of an online interdisciplinary intervention for mental health promotion: a randomized controlled trial.

BACKGROUND: There is an urgent need for efficacious interventions to combat the global mental health crisis, and mental health promotion and primary prevention approaches are paramount. The aim of this study is to examine whether an online interdisciplinary intervention that incorporates evidence-based strategies from the disciplines of Lifestyle Medicine and Positive Psychology improves measures of mental health and emotional wellness. METHODS: A randomized controlled trial with a wait-list control (N = 425, aged 46.97 ± 14.5, 69.9% females) was conducted in Australia and New Zealand. The intervention group participated in a 10-week online interdisciplinary intervention. Primary outcome measures of mental health and emotional wellness were taken at baseline (Week 1), post-intervention (Week 12), and 12 weeks post-intervention (Week 24). The wait-list control completed the same assessments. RESULTS: General Linear Modelling analyses indicated that the intervention group experienced significantly greater improvements than the wait-list control group over time in all outcome measures: mental health (F(319) = 7.326, p = 0.007) and vitality (F(319) = 9.445, p = 0.002) subscales of the Short Form Survey (SF-36); depression (F(319) = 7.841, p = 0.005), anxiety (F(319) = 4.440, p = 0.36) and stress (F(319) = 12.494, p < 0.001) scales of the Depression, Anxiety and Stress Scale (DASS-21); and life satisfaction (F(319) = 8.731, p = 0.003) as measured by the Satisfaction With Life Scale. Within the intervention group, significant improvements were observed from Week 1 to 12 in all outcome measures: mental health (10%, t(167) = - 6.423), p < 0.001, dz = 0.50), vitality (22%, t(167) = - 7.043, p < 0.001, dz = 0.54), depression (- 41%, t(167) = 6.189, p < 0.001, dz = 0.48), anxiety (- 38%, t(167) = 5.030, p < 0.001, dz = 0.39), stress (- 31%, t(167) = 6.702, p < 0.001, dz = 0.52) and life satisfaction (8%, t(167) = - 6.199, p < 0.001, dz = 0.48). Improvements in the outcome measures remained significant in the intervention group at 12 weeks post-intervention. CONCLUSION: The online interdisciplinary intervention improved measures of mental health and emotional wellness suggesting that such interventions may be useful for mental health promotion and prevention. Trial registration The Australian New Zealand Clinical Trials Registry. ACTRN12619000993190. Registered on 12 July 2019 (Retrospectively registered). The ANZCTRN is part of the WHO Primary Registries.

Backshore nourishment of a beach degraded by off-road vehicles: Ecological impacts and benefits.

Worldwide, spoil from maintenance dredging of navigation channels is increasingly used to opportunistically nourish beaches. This is often justified on the presumption that nourishment will improve public beach amenity and restore sandy beach habitat. However, this is not necessarily the case, especially for beaches that do not have an immediate threat of significant erosion. We addressed the ecological impacts and benefits of a backshore sand nourishment project conducted along an off-road vehicle (ORV) damaged section of Blacksmiths Beach, New South Wales, Australia. Sediment, sourced from dredging the inlet of nearby Lake Macquarie, was placed on the foredune, ORVs were excluded and low-density vegetation was planted. Sampling before and after the management interventions, at the Impact (nourished) site, two Control sites (with ORVs), and two Reference sites (without ORVs), assessed ecological impacts of nourishment and the efficacy of the interventions in rehabilitating vegetation and invertebrate communities degraded by ORVs. Nourishment initially had large negative impacts on vegetation cover, as well as on invertebrate abundance and richness. Recovery to a pre-nourished state was, however, observed for vegetation cover after 9 months and invertebrate communities after 21 months. Nevertheless, by the end of our study that extended 21 months post-nourishment and ORV exclusion, there was no evidence of change in the nourished site towards the state of Reference sites. Overall, our study suggests that small-scale backshore sand nourishments of ocean beaches may have only short-term negative impacts on foredune ecosystems when accompanied with some replanting. Nevertheless, where the frequency of sand disposals is greater than the required recovery time, or cumulative effects amass, longer-term or sustained impacts may occur. Our study does not support the efficacy of sand nourishment as a tool for ecological restoration, at least in the short term, without sustained replanting and weeding efforts aimed at reinstating the vegetation community.

The cyclohedron test for finding periodic genes in time course expression studies.

The problem of finding periodically expressed genes from time course microarray experiments is at the center of numerous efforts to identify the molecular components of biological clocks. We present a new approach to this problem based on the cyclohedron test, which is a rank test inspired by recent advances in algebraic combinatorics. The test has the advantage of being robust to measurement errors, and can be used to ascertain the significance of top-ranked genes. We apply the test to recently published measurements of gene expression during mouse somitogenesis and find 32 genes that collectively are significant. Among these are previously identified periodic genes involved in the Notch/FGF and Wnt signaling pathways, as well as novel candidate genes that may play a role in regulating the segmentation clock. These results confirm that there are an abundance of exceptionally periodic genes expressed during somitogenesis. The emphasis of this paper is on the statistics and combinatorics that underlie the cyclohedron test and its implementation within a multiple testing framework.

An open source solution for an in-house built dynamic platform for the validation of stereotactic ablative body radiotherapy for VMAT and IMRT.

An in-house solution for the verification of dose delivered to a moving phantom as required for the clinical implementation of lung stereotactic ablative body radiation therapy was developed. The superior-inferior movement required to simulate tumour motion during a normal breathing cycle was achieved via the novel use of an Arduino Uno™, a low-cost open-source microcontroller board connected to a high torque servo motor. Slow CT imaging was used to acquire the image set and a 4D cone beam CT (4D-CBCT) verified the efficacy of contoured margins before treatment on the moving phantom. Treatment fields were delivered to a section of a CIRS™ anthropomorphic phantom. Dose verification to the dynamic phantom with Gafchromic EBT3 film using 3 %-1 mm gamma analysis acceptance criteria registered an absolute dose pass rate for IMRT and VMAT of 98 and 96.6 %, respectively. It was verified that 100 % of the PTV received the prescribed dose of 12 Gy per fraction using the dynamic phantom, and no major discrepancy between planned and measured results due to interplay between multileaf collimator sequences and target motion was observed. This study confirmed that the use of an in-house solution using open source hardware and software with existing quality assurance equipment was appropriate in validating a new treatment technique.

Post-upgrade testing on a radiotherapy oncology information system with an embedded record and verify system following the IAEA Human Health Report No. 7 recommendations.

Record and verify (R&V) systems have proven that their application in radiotherapy clinics leads to a significant reduction in mis-treatments of patients. The purpose of this technical note is to share our experience of acceptance testing, commissioning and setting up a quality assurance programme for the MOSAIQ® oncology information system and R&V system after upgrading from software version 2.41 to 2.6 in a multi-vendor, multi-site environment. Testing was guided primarily by the IAEA Human Report No. 7 recommendations, but complemented by other departmental workflow specific tests. To the best of our knowledge, this is the first time successful implementation of the IAEA Human Health Report Series No. 7 recommendations have been reported in the literature.

1,1-Olefin-bridged bis-(2-indenyl) metallocenes of titanium and zirconium.

Tetrasubstituted alkenes bearing geminal 2-indenyl substituents--9-[bis(1H-inden-2-yl)methylidene]-9H-fluorene (6), 2,2'-(2,2-diphenylethene-1,1-diyl)-bis(1H-indene) (7), and 2,2'-(2-propylpent-1-ene-1,1-diyl)-bis(1H-indene) (8) have been synthesized and metallated to form a new class of ansa titanium and zirconium metallocene complexes containing a single sp(2)-hybridized carbon bridge. The synthesis of the tetramethylated bis-indenyl Zr-analog is described. In addition, the 1,1-bis-indenyl ethylene is prepared and the Zr complex is modified by olefin metathesis. X-ray structure analyses reveal strained η(5) sandwich complexes with highly open metal centers. These complexes have proven active in the polymerization of ethylene and its copolymerization with 1-hexene.

Titanium "constrained geometry" complexes with pendant arene groups.

The synthesis of the proligands C(5)Me(4)HSiMe(2)N(H)R) (R = CMe(2)Ph 1, 2-C(6)H(4)Ph 2) was accomplished via a straightforward salt metathesis reaction of the appropriate lithium amide and ClSiMe(2)(C(5)Me(5)H). Generation of the dilithio salt and reaction with TiCl(3)·(THF)(3) followed by oxidation gave C(5)Me(4)SiMe(2)N(C(6)H(4)Ph)TiCl(2) (3) in low yield. In contrast, deprotonation of 1 and 2 and reaction with (Me(2)N)(2)TiCl(2) afforded C(5)Me(4)(SiMe(2)NR)Ti(NMe(2))(2) (R = CMe(2)Ph 4, 2-C(6)H(4)Ph 5), respectively, in good yields Treatment with MeI gave the analogs C(5)Me(4)(SiMe(2)NR)TiI(2) (R = CMe(2)Ph 6, 2-C(6)H(4)Ph 7). Reduction of 7 with potassium graphite afforded C(5)Me(4)(SiMe(2)NC(6)H(4)Ph)Ti 8. Treatment of 6 and 7 with MeMgBr afforded C(5)Me(4)(SiMe(2)NR)TiMe(2) (R = CMe(2)Ph 9, 2-C(6)H(4)Ph 10). Complexes 9 and 10 in combination with the activator [Ph(3)C][B(C(6)F(5))(4)] catalyzed the polymerization of styrene and ethylene. Copolymerization was also investigated. While the catalyst derived from 10 showed poor activity, compound 9 showed markedly higher activity than 10 and (C(5)Me(4))SiMe(2)(NtBu)]TiMe(2).

Ring-opening of cyclopropanes by "frustrated Lewis pairs".

Reactions of phosphine/borane frustrated Lewis pairs with cyclopropanes result in the ring opening, yielding phosphonium borate products.

Rapid assembly of vinigrol's unique carbocyclic skeleton.

Detailed in this account are our efforts toward the total synthesis of vinigrol. A highly expedient and convergent synthetic approach made possible by the use of a strategic oxidative dearomatization reaction coupled with a series of ensuing substrate controlled transformations is discussed.

Comparison of pattern detection methods in microarray time series of the segmentation clock.

While genome-wide gene expression data are generated at an increasing rate, the repertoire of approaches for pattern discovery in these data is still limited. Identifying subtle patterns of interest in large amounts of data (tens of thousands of profiles) associated with a certain level of noise remains a challenge. A microarray time series was recently generated to study the transcriptional program of the mouse segmentation clock, a biological oscillator associated with the periodic formation of the segments of the body axis. A method related to Fourier analysis, the Lomb-Scargle periodogram, was used to detect periodic profiles in the dataset, leading to the identification of a novel set of cyclic genes associated with the segmentation clock. Here, we applied to the same microarray time series dataset four distinct mathematical methods to identify significant patterns in gene expression profiles. These methods are called: Phase consistency, Address reduction, Cyclohedron test and Stable persistence, and are based on different conceptual frameworks that are either hypothesis- or data-driven. Some of the methods, unlike Fourier transforms, are not dependent on the assumption of periodicity of the pattern of interest. Remarkably, these methods identified blindly the expression profiles of known cyclic genes as the most significant patterns in the dataset. Many candidate genes predicted by more than one approach appeared to be true positive cyclic genes and will be of particular interest for future research. In addition, these methods predicted novel candidate cyclic genes that were consistent with previous biological knowledge and experimental validation in mouse embryos. Our results demonstrate the utility of these novel pattern detection strategies, notably for detection of periodic profiles, and suggest that combining several distinct mathematical approaches to analyze microarray datasets is a valuable strategy for identifying genes that exhibit novel, interesting transcriptional patterns.

Induction and repair of zinc-finger nuclease-targeted double-strand breaks in Caenorhabditis elegans somatic cells.

Zinc-finger nucleases are chimeric proteins consisting of engineered zinc-finger DNA-binding motifs attached to an endonuclease domain. These proteins can induce site-specific DNA double-strand breaks in genomic DNA, which are then substrates for cellular repair mechanisms. Here, we demonstrate that engineered zinc-finger nucleases function effectively in somatic cells of the nematode Caenorhabditis elegans. Although gene-conversion events were indistinguishable from uncut DNA in our assay, nonhomologous end joining resulted in mutations at the target site. A synthetic target on an extrachromosomal array was targeted with a previously characterized nuclease, and an endogenous genomic sequence was targeted with a pair of specifically designed nucleases. In both cases, approximately 20% of the target sites were mutated after induction of the corresponding nucleases. Alterations in the extrachromosomal targets were largely products of end-filling and blunt ligation. By contrast, alterations in the chromosomal target were mostly deletions. We interpret these differences to reflect the abundance of homologous templates present in the extrachromosomal arrays versus the paucity of such templates for repair of chromosomal breaks. In addition, we find evidence for the involvement of error-prone DNA synthesis in both homologous and nonhomologous pathways of repair. DNA ligase IV is required for efficient end joining, particularly of blunt ends. In its absence, a secondary end-joining pathway relies more heavily on microhomologies in producing deletions.

Influence of axial length of normal eyes on PERG.

The influence of the axial length (AL) of the eye on flash electroretinogram (ERG) responses has been well established in the literature, suggesting an association between ERG abnormalities with myopia (AL > 25 mm). The aim of our present study was to determine whether the AL of normal eyes can also influence the pattern electroretinogram (PERG) on normal subjects. Thirty-nine normal volunteers were subjected to PERG measurements following the standard set by the International Society for Clinical Electrophysiology of Vision (ISCEV). The AL of the eyeball was measured using a TOMEY ultrasonic A scanner. Each volunteer had a complete ophthalmic examination including visual acuity, refraction, intraocular pressure, visual field, colour vision, orthoptic assessment and retinal photographs and had a best corrected visual acuity of 6/9 or better. Only one eye from each of the 39 normal volunteers was included in the statistical analysis of the results. The normal volunteer group had a mean P50 amplitude of 3.8 +/- 1.1 SD microV. The range of AL was between 21.8 and 25.7 mm (mean = 23.8 +/- 1.0 SD mm). Overall findings obtained from this investigation indicate a significant correlation between the AL of normal eyes and the PERG P50 amplitude (Spearman rank correlation coefficient r = -0.413, p < 0.01). The correlation accounts for 17% of the variance observed in the 39 amplitude values. This confirms the current hypothesis that the PERG amplitude is inversely related to axial length and means that AL should be considered when interpreting PERG amplitudes.

Synthesis and explosive decomposition of organometallic dehydro[18]annulenes: an access to carbon nanostructures.

The synthesis of eight new cyclobutadiene or ferrocene-fused organometallic dehydroannulenes is reported. Cadiot-type coupling of a 1-bromoethynyl-2-silylethynylbenzene derivative to an organometallic diyne (1,2-diethynyl-3,4-bis(trimethylsilyl)cyclobutadiene(cyclopentadienyl )cobalt or 1,2-diethynylferrocene) is followed by deprotection and Cu(OAc)(2)-promoted ring closure. Five of the organometallic dehydroannulenes were structurally characterized. Three of the novel cycles explode at temperatures from 196 to 293 degrees C and form insoluble carbon materials. The soot produced from 13a shows a high abundance of onion-like carbon nanostructures. The nanostructures were characterized by high-resolution transmission electron microscopy.