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Switching noise generated by digital circuits can degrade analog circuit performance in mixed-signal integrated circuits (ICs). In an analog-to-digital converter (ADC), one major source of switching noise is digital output drivers. Traditional methods for mitigating this problem mostly have been to isolate the analog and digital circuits to minimize digital noise coupling into sensitive analog nodes. This paper presents two fully digital and adaptive algorithms, which find and cancel errors due to switching noise coupling at the output of an ADC without using noise sensors. To demonstrate the operation of these algorithms, a 12-bit, 40-MS/s pipelined ADC has been designed and fabricated in 0.18-μm CMOS process. The system consists of an ADC with its own output drivers, and eight other independent digital output drivers (noise buffers) that can be programmed to produce four different kinds of switching noise. The switching noise cancellation (SNC) algorithm estimates noise parameters and stores them in look-up tables. At the ADC output, the effects of switching noise are digitally removed to recover the input samples. Test results show that the ADC achieves a signal-to-noise-and-distortion-ratio (SNDR) of 64.9 dB with all of the noise-generating buffers off. With the noise buffers on, the worst case SNDR before and after SNC is 51.9 dB and 63.7 dB, respectively. © 1966-2012 IEEE.

The effects of salt water exposure at deep ocean depth pressures when coupled with low temperatures on the material characteristics of three unique additively manufactured polymers has been investigated through a detailed experimental approach. The polymers in the study were manufactured utilizing both Vat Photopolymerization and Material Extrusion printing techniques. The Material Extrusion process was utilized to produce material specimens of Stratasys ULTEM 9085 and Markforged Onyx while the Vat Photopolymerization process was used to produce specimens of Accura ClearVue. The ULTEM 9085 and Markforged Onyx are filament based polymers and the ClearVue is a liquid based resin. The specimens were first submerged in a high pressure, salt water bath of 3.5% NaCl solution at 34.5 MPa (5000 lb/in2) for a total exposure time of 60 days to determine the water absorption characteristics. Subsequent to the salt water exposure at high pressure, the specimens were evaluated to determine changes in tension, compression, flexure, and in-plane fracture properties. To determine the effects of water saturation and low temperature coupling, the mechanical testing was performed at temperatures of 20 °C, 0 °C and −20 °C in both dry and saturated conditions. Additionally, non-destructive testing in the form of TeraHertz and FIRT imaging was conducted to analyze the physical material changes through the thickness of the material due to the saline water absorption. To quantify the change in material storage and loss moduli properties, Dynamic Mechanical Analysis (DMA) characterization was performed on each of the AM polymers in dry and saturated states. The DMA testing also quantified changes in the Glass Transition Temperature because of salt water exposure. In summary, The current study investigates the effects of coupled long term/high pressure salt water exposure with low temperatures on the mechanical and material characteristics of three unique AM polymers by: (1) immersing the materials in a salt water solution at 34.5 MPa for 60 days, (2) Conducting post exposure mechanical testing on the materials at 0 °C and −20 °C with comparisons to 20 °C testing on dry specimens, and quantifies changes in material properties through DMA experiments. The results from all testing in the study show that high pressure salt water exposure when coupled with low temperatures has unique effects on each of the materials considered in the study and careful consideration to each parameter must be given based on the material type when components will be employed in marine operations.

Abstract Aedes aegypti is the main vector of several major pathogens including dengue, Zika and chikungunya viruses. Classical mosquito control strategies utilizing insecticides are threatened by rising resistance. This has stimulated interest in new genetic systems such as gene drivesHere, we test the regulatory sequences from the Ae. aegypti benign gonial cell neoplasm (bgcn) homolog to express Cas9 and a separate multiplexing sgRNA-expressing cassette inserted into the Ae. aegypti kynurenine 3-monooxygenase (kmo) gene. When combined, these two elements provide highly effective germline cutting at the kmo locus and act as a gene drive. Our target genetic element drives through a cage trial population such that carrier frequency of the element increases from 50% to up to 89% of the population despite significant fitness costs to kmo insertions. Deep sequencing suggests that the multiplexing design could mitigate resistance allele formation in our gene drive system.

The orientation ordering and assembly behavior of silica–nickel Janus particles in a static external magnetic field were probed by ultra small-angle X-ray scattering (USAXS). Even in a weak applied field, the net magnetic moments of the individual particles aligned in the direction of the field, as indicated by the anisotropy in the recorded USAXS patterns. X-ray photon correlation spectroscopy (XPCS) measurements on these suspensions revealed that the corresponding particle dynamics are primarily Brownian diffusion [Zinn, Sharpnack & Narayanan (2023). Soft Matter, 19, 2311–2318]. At higher fields, the magnetic forces led to chain-like configurations of particles, as indicated by an additional feature in the USAXS pattern. A theoretical framework is provided for the quantitative interpretation of the observed anisotropic scattering diagrams and the corresponding degree of orientation. No anisotropy was detected when the magnetic field was applied along the beam direction, which is also replicated by the model. The method presented here could be useful for the interpretation of oriented scattering patterns from a wide variety of particulate systems. The combination of USAXS and XPCS is a powerful approach for investigating asymmetric colloidal particles in external fields.

An experimental study has been performed to investigate the coupled effects of hydrostatic deep depth pressure and sustained salt-water immersion on the mechanical properties and material structure of additively manufactured (AM) polymer based materials. The materials that were evaluated in the study were produced by both the material extrusion and vat photopolymerization printing methods. The material extrusion materials consisted of Stratasys ULTEM 9085 and Markforged Onyx and the vat photopolymerization material was Accura ClearVue resin. Water immersion was conducted with 3.5% NaCl solution at room temperature under a pressure of 34.5 MPa in a novel test facility for long duration, high pressure water saturation. The respective materials were characterized in three conditions: (1) baseline with no water saturation, (2) 30 day water immersion, and (3) 60 day water immersion. The change in mechanical properties as a function of aging time was quantified through controlled laboratory testing, namely tension, compression, flexure, and in-plane fracture toughness. Additionally, a microscopic evaluation was performed to evaluate the physical material degradation between layer bonding due to the saline water absorption. The significant findings of the study highlight that salt water immersion has differing effects on additively manufactured materials based on the material composition of the base material and thus significant consideration must be given to material selection in marine environments.

Recent advances in deep sequencing technologies have revealed that, while less than 2% of the human genome is transcribed into mRNA for protein synthesis, over 80% of the genome is transcribed, leading to the production of large amounts of noncoding RNAs (ncRNAs). It has been shown that ncRNAs, especially long non-coding RNAs (lncRNAs), may play crucial regulatory roles in gene expression. As one of the first isolated and reported lncRNAs, H19 has gained much attention due to its essential roles in regulating many physiological and/or pathological processes including embryogenesis, development, tumorigenesis, osteogenesis, and metabolism. Mechanistically, H19 mediates diverse regulatory functions by serving as competing endogenous RNAs (CeRNAs), Igf2/H19 imprinted tandem gene, modular scaffold, cooperating with H19 antisense, and acting directly with other mRNAs or lncRNAs. Here, we summarized the current understanding of H19 in embryogenesis and development, cancer development and progression, mesenchymal stem cell lineage-specific differentiation, and metabolic diseases. We discussed the potential regulatory mechanisms underlying H19's functions in those processes although more in-depth studies are warranted to delineate the exact molecular, cellular, epigenetic, and genomic regulatory mechanisms underlying the physiological and pathological roles of H19. Ultimately, these lines of investigation may lead to the development of novel therapeutics for human diseases by exploiting H19 functions.

CRISPR/Cas9-based homing gene drives have emerged as a potential new approach to mosquito control. Here the authors use transgenic lines with germline-specific regulatory elements to express Cas9 and achieve up to 94% inheritance bias, closing the gap between A. aegyptidrives and the highly efficient drives observed in Anopheles species.

Total shoulder arthroplasty is an increasingly popular option for the treatment of glenohumeral arthritis. Historically, the effectiveness of the procedure has largely been determined by the long-term stability of the glenoid component. Glenoid component loosening can lead to clinically concerning complications including pain with movement, loss of function, and accumulation of debris which may require surgery to revise. In response, there has been a push to optimize the design of the glenoid prosthesis. Traditional contemporary glenoid components use pegs for fixation and are made entirely of polyethylene. Variations on the standard implant include keeled, metal-backed, hybrid, augmented, and inlay designs. There is a wealth of biomechanical and clinical studies that report on the effectiveness of these different designs. The purpose of this review is to summarize existing literature regarding glenoid component design and identify key areas for future research. Knowledge of the rationale underlying glenoid design will help surgeons select the best component for their patients and optimize outcomes following TSA.

Abstract Culex quinquefasciatus Say is a mosquito distributed in both tropical and subtropical regions of the world. It is a night-active, opportunistic blood-feeder and vectors many animal and human diseases, including West Nile Virus and avian malaria. Current vector control methods (e.g. physical/chemical) are increasingly ineffective; use of insecticides also imposes hazards to both human and ecosystem health. Advances in genome editing have allowed the development of genetic insect control methods, which are species-specific and, theoretically, highly effective. CRISPR/Cas9 is a bacteria-derived programmable gene editing tool that is functional in a range of species. We describe the first successful germline gene knock-in by homology dependent repair in C. quinquefasciatus. Using CRISPR/Cas9, we integrated an sgRNA expression cassette and marker gene encoding a fluorescent protein fluorophore (Hr5/IE1-DsRed, Cq7SK-sgRNA) into the kynurenine 3-monooxygenase (kmo) gene. We achieved a minimum transformation rate of 2.8%, similar to rates in other mosquito species. Precise knock-in at the intended locus was confirmed. Insertion homozygotes displayed a white eye phenotype in early-mid larvae and a recessive lethal phenotype by pupation. This work provides an efficient method for engineering C. quinquefasciatus, providing a new tool for developing genetic control tools for this vector.

The increasing prevalence of insecticide resistance and the ongoing global burden of vector-borne diseases have encouraged new efforts in mosquito control. For Aedes aegypti, the most important arboviral vector, integration rates achieved in Cas9-based knock-ins so far have been rather low, highlighting the need to understand gene conversion patterns and other factors that influence homology-directed repair (HDR) events in this species. In this study, we report the effects of sequence mismatches or donor template forms on integration rates. We found that modest sequence differences between construct homology arms [DNA sequence in the donor template which resembles the region flanking the target cut] and genomic target comprising 1.2% nucleotide dissimilarity (heterology) significantly reduced integration rates. While most integrations (59-88%) from plasmid templates were the result of canonical [on target, perfect repair] HDR events, no canonical events were identified from other donor types (i.e. ssDNA, biotinylated ds/ssDNA). Sequencing of the transgene flanking region in 69 individuals with canonical integrations revealed 60% of conversion tracts to be unidirectional and extend up to 220 bp proximal to the break, though in three individuals bidirectional conversion of up to 725 bp was observed.

With the significant financial burden of chronic cutaneous wounds on the healthcare system, not to the personal burden mention on those individuals afflicted, it has become increasingly essential to improve our clinical treatments. This requires the translation of the most recent benchtop approaches to clinical wound repair as our current treatment modalities have proven insufficient. The most promising potential treatment options rely on stem cell-based therapies. Stem cell proliferation and signaling play crucial roles in every phase of the wound healing process and chronic wounds are often associated with impaired stem cell function. Clinical approaches involving stem cells could thus be utilized in some cases to improve a body's inhibited healing capacity. We aim to present the laboratory research behind the mechanisms and effects of this technology as well as current clinical trials which showcase their therapeutic potential. Given the current problems and complications presented by chronic wounds, we hope to show that developing the clinical applications of stem cell therapies is the rational next step in improving wound care. Keywords: Chronic inflammation, Chronic wounds, Growth factors, Personalized medicine, Skin, Stem cells, Wound healing

Culex quinquefasciatus Say is an opportunistic blood feeder with a wide geographic distribution which is also a major vector for a range of diseases of both animals and humans. CRISPR/Cas technologies have been applied to a wide variety of organisms for both applied and basic research purposes. CRISPR/Cas methods open new possibilities for genetic research in non-model organisms of public health importance. In this work we have adapted microinjection techniques commonly used in other mosquito species to Culex quinquefasciatus, and have shown these to be effective at generating homozygous knock-out mutations of a target gene in one generation. This is the first description of the kmo gene and mutant phenotype in this species.

Different phoretic effects have been widely exploited for designing self-propelled colloidal systems, but the underlying wave vector dependent dynamics has been little investigated. In this work, the out-of-equilibrium dynamics of colloids in near-critical liquid mixtures undergoing spinodal phase separation was probed by x-ray photon correlation spectroscopy (XPCS). The emergent dynamics of charge stabilized silica and silica-nickel Janus particles upon a temperature jump into the two-phase region of the solvent mixture displayed similar features at the initial stage. In both systems, the phoretic dynamics is dominated by velocity fluctuations induced by the solvent concentration fluctuations and the hydrodynamic flow during the coarsening process. Furthermore, relaxation rates of the diffusive part of the dynamics manifested an anomalous wave vector dependence akin to the superdiffusive behavior with an effective diffusion coefficient significantly larger than the Brownian limit. For smaller temperature jumps, velocity fluctuations exhibited a broader distribution with silica and Janus colloids showing qualitatively different behavior. The velocity fluctuations decayed with time and the dynamics reverted to diffusive behavior upon completion of the phase separation. Presented results illustrate the ability to probe faster collective dynamics pertinent to active colloids using multispeckle XPCS.

A series of bis(4-alkoxyphenyl) viologen bis(triflimide) salts with alkoxy chains of different lengths were synthesized by the metathesis reaction of respective bis(4-alkoxyphenyl) viologen dichloride salts, which were in turn prepared from the reaction of Zincke salt with the corresponding 4-n-alkoxyanilines, with lithium triflimide in methanol. Their chemical structures were characterized by 1H and 13C nuclear magnetic resonance spectra and elemental analysis. Their thermotropic liquid-crystalline (LC) properties were examined by differential scanning calorimetry, polarizing optical microscopy, and variable temperature X-ray diffraction. Salts with short length alkoxy chains had crystal-to-liquid transitions. Salts of intermediate length alkoxy chains showed both crystal-to-smectic A (SmA) transitions, Tms, and SmA-to-isotropic transitions, Tis. Those with longer length of alkoxy chains had relatively low Tms at which they formed the SmA phases that persisted up to the decomposition at high temperatures. As expected, all of them had excellent thermal stabilities in the temperature range of 330–370 °C. Their light-emitting properties in methanol were also included.

Abstract Background Over the past decade policy makers have emphasised the importance of healthcare technology in the management of long-term conditions. Mobile-phone based assessment may be one method of facilitating clinically- and cost-effective intervention, and increasing the autonomy and independence of service users. Recently, text-message and smartphone interfaces have been developed for the real-time assessment of symptoms in individuals with schizophrenia. Little is currently understood about patients’ perceptions of these systems, and how they might be implemented into their everyday routine and clinical care. Method 24 community based individuals with non-affective psychosis completed a randomised repeated-measure cross-over design study, where they filled in self-report questions about their symptoms via text-messages on their own phone, or via a purpose designed software application for Android smartphones, for six days. Qualitative interviews were conducted in order to explore participants’ perceptions and experiences of the devices, and thematic analysis was used to analyse the data. Results Three themes emerged from the data: i) the appeal of usability and familiarity, ii) acceptability, validity and integration into domestic routines, and iii) perceived impact on clinical care. Although participants generally found the technology non-stigmatising and well integrated into their everyday activities, the repetitiveness of the questions was identified as a likely barrier to long-term adoption. Potential benefits to the quality of care received were seen in terms of assisting clinicians, faster and more efficient data exchange, and aiding patient-clinician communication. However, patients often failed to see the relevance of the systems to their personal situations, and emphasised the threat to the person centred element of their care. Conclusions The feedback presented in this paper suggests that patients are conscious of the benefits that mobile-phone based assessment could bring to clinical care, and that the technology can be successfully integrated into everyday routine. However, it also suggests that it is important to demonstrate to patients the personal, as well as theoretical, benefits of the technology. In the future it will be important to establish whether clinical practitioners are able to use this technology as part of a personalised mental health regime.

Abstract Background Dengue is the most common arboviral disease of humans, with more than one third of the world’s population at risk. Accurate prediction of dengue outbreaks may lead to public health interventions that mitigate the effect of the disease. Predicting infectious disease outbreaks is a challenging task; truly predictive methods are still in their infancy. Methods We describe a novel prediction method utilizing Fuzzy Association Rule Mining to extract relationships between clinical, meteorological, climatic, and socio-political data from Peru. These relationships are in the form of rules. The best set of rules is automatically chosen and forms a classifier. That classifier is then used to predict future dengue incidence as either HIGH (outbreak) or LOW (no outbreak), where these values are defined as being above and below the mean previous dengue incidence plus two standard deviations, respectively. Results Our automated method built three different fuzzy association rule models. Using the first two weekly models, we predicted dengue incidence three and four weeks in advance, respectively. The third prediction encompassed a four-week period, specifically four to seven weeks from time of prediction. Using previously unused test data for the period 4–7 weeks from time of prediction yielded a positive predictive value of 0.686, a negative predictive value of 0.976, a sensitivity of 0.615, and a specificity of 0.982. Conclusions We have developed a novel approach for dengue outbreak prediction. The method is general, could be extended for use in any geographical region, and has the potential to be extended to other environmentally influenced infections. The variables used in our method are widely available for most, if not all countries, enhancing the generalizability of our method.

Abstract Background Semi-structured interview scales for psychosis are the gold standard approach to assessing psychotic and other symptoms. However, such assessments have limitations such as recall bias, averaging, insensitivity to change and variable interrater reliability. Ambulant, real-time self-report assessment devices may hold advantages over interview measures, but it needs to be shown that the data thus collected are valid, and the collection method is acceptable, feasible and safe. We report on a monitoring system for the assessment of psychosis using smartphone technology. The primary aims were to: i) assess validity through correlations of item responses with those on widely accepted interview assessments of psychosis, and ii) examine compliance to the procedure in individuals with psychosis of varying severity. Methods A total of 44 participants (acute or remitted DSM-4 schizophrenia and related disorders, and prodromal) completed 14 branching self-report items concerning key psychotic symptoms on a touch-screen mobile phone when prompted by an alarm at six pseudo-random times, each day, for one week. Face to face PANSS and CDS interviews were conducted before and after the assessment period blind to the ambulant data. Results Compliance as defined by completion of at least 33% of all possible data-points over seven days was 82%. In the 36 compliant participants, 5 items (delusions, hallucinations, suspiciousness, anxiety, hopelessness) showed moderate to strong (rho 0.6-0.8) associations with corresponding items from interview rating scales. Four items showed no significant correlation with rating scales: each was an item based on observable behaviour. Ambulant ratings showed excellent test-retest reliability and sensitivity to change. Conclusions Ambulatory monitoring of symptoms several times daily using smartphone software applications represents a feasible and valid way of assessing psychotic phenomena for research and clinical management purposes. Further evaluation required over longer assessment periods, in clinical trials and service settings.

Abstract Background Emerging public health threats often originate in resource-limited countries. In recognition of this fact, the World Health Organization issued revised International Health Regulations in 2005, which call for significantly increased reporting and response capabilities for all signatory nations. Electronic biosurveillance systems can improve the timeliness of public health data collection, aid in the early detection of and response to disease outbreaks, and enhance situational awareness. Methods As components of its Suite for Automated Global bioSurveillance (SAGES) program, The Johns Hopkins University Applied Physics Laboratory developed two open-source, electronic biosurveillance systems for use in resource-limited settings. OpenESSENCE provides web-based data entry, analysis, and reporting. ESSENCE Desktop Edition provides similar capabilities for settings without internet access. Both systems may be configured to collect data using locally available cell phone technologies. Results ESSENCE Desktop Edition has been deployed for two years in the Republic of the Philippines. Local health clinics have rapidly adopted the new technology to provide daily reporting, thus eliminating the two-to-three week data lag of the previous paper-based system. Conclusions OpenESSENCE and ESSENCE Desktop Edition are two open-source software products with the capability of significantly improving disease surveillance in a wide range of resource-limited settings. These products, and other emerging surveillance technologies, can assist resource-limited countries compliance with the revised International Health Regulations.

Abstract Background Command hallucinations are among the most distressing, high risk and treatment resistant symptoms for people with psychosis; however, currently, there are no evidence-based treatment options available for this group. A cognitive therapy grounded in the principles of the Social Rank Theory, is being evaluated in terms of its effectiveness in reducing harmful compliance with command hallucinations. Methods/Design This is a single blind, intention-to-treat, multi-centre, randomized controlled trial comparing Cognitive Therapy for Command Hallucinations + Treatment as Usual with Treatment as Usual alone. Eligible participants have to fulfil the following inclusion criteria: i) ≥16 years; ii) ICD-10 diagnosis of schizophrenia or related disorder; iii) command hallucinations for at least 6 months leading to risk of harm to self or others. Following the completion of baseline assessments, eligible participants will be randomly allocated to either the Cognitive Therapy for Command Hallucinations + Treatment as Usual group or the Treatment as Usual group. Outcome will be assessed at 9 and 18 months post randomization with assessors blind to treatment allocation. The primary outcome is compliance behaviour and secondary outcomes include beliefs about voices' power, distress, psychotic symptoms together with a health economic evaluation. Qualitative interviews with services users will explore the acceptability of Cognitive Therapy for Command Hallucinations. Discussion Cognitive behaviour therapy is recommended for people with psychosis; however, its focus and evaluation has primarily revolved around the reduction of psychotic symptoms. In this trial, however, the focus of the cognitive behavioural intervention is on individuals' appraisals, behaviour and affect and not necessarily symptoms; this is also reflected in the outcome measures used. If successful, the results will mark a significant breakthrough in the evidence base for service users and clinicians and will provide a treatment option for this group where none currently exist. The trial will open the way for further breakthrough work with the 'high risk' population of individuals with psychosis, which we would intend to pursue. Trial registration ISRCTN: ISRCTN62304114

Abstract Background Young people with neurological impairments such as epilepsy are known to receive less adequate services compared to young people with other long-term conditions. The time (age 13-19 years) around transition to adult services is particularly important in facilitating young people's self-care and ongoing management. There are epilepsy specific, biological and psycho-social factors that act as barriers and enablers to information exchange and nurturing of self-care practices. Review objectives were to identify what is known to be effective in delivering information to young people age 13-19 years with epilepsy and their parents, to describe their experiences of information exchange in healthcare contexts, and to identify factors influencing positive and negative healthcare communication. Methods The Evidence for Policy and Practice Information Coordinating Centre systematic mixed-method approach was adapted to locate, appraise, extract and synthesise evidence. We used Ley's cognitive hypothetical model of communication and subsequently developed a theoretical framework explaining information exchange in healthcare contexts. Results Young people and parents believed that healthcare professionals were only interested in medical management. Young people felt that discussions about their epilepsy primarily occurred between professionals and parents. Epilepsy information that young people obtained from parents or from their own efforts increased the risk of epilepsy misconceptions. Accurate epilepsy knowledge aided psychosocial adjustment. There is some evidence that interventions, when delivered in a structured psycho-educational, age appropriate way, increased young people's epilepsy knowledge, with positive trend to improving quality of life. We used mainly qualitative and mixed-method evidence to develop a theoretical framework explaining information exchange in clinical encounters. Conclusions There is a paucity of evidence reporting effective interventions, and the most effective ways of delivering information/education in healthcare contexts. No studies indicated if improvement was sustained over time and whether increased knowledge was effective in improving in self-care. Current models of facilitating information exchange and self-care around transition are not working well. There is an urgent need for further studies to develop and evaluate interventions to facilitate successful information exchange, and follow young people over time to see if interventions showing early promise are effective in the medium to long-term.

Abstract Background Recent developments have made screening tests for foetal abnormalities available earlier in pregnancy and women have a range of testing options accessible to them. It is now recommended that all women, regardless of their age, are provided with information on prenatal screening tests. General Practitioners (GPs) are often the first health professionals a woman consults in pregnancy. As such, GPs are well positioned to inform women of the increasing range of prenatal screening tests available. The aim of this study was to explore GPs experience of informing women of prenatal genetic screening tests for foetal abnormality. Methods A qualitative study consisting of four focus groups was conducted in metropolitan and rural Victoria, Australia. A discussion guide was used and the audio-taped transcripts were independently coded by two researchers using thematic analysis. Multiple coders and analysts and informant feedback were employed to reduce the potential for researcher bias and increase the validity of the findings. Results Six themes were identified and classified as 'intrinsic' if they occurred within the context of the consultation or 'extrinsic' if they consisted of elements that impacted on the GP beyond the scope of the consultation. The three intrinsic themes were the way GPs explained the limitations of screening, the extent to which GPs provided information selectively and the time pressures at play. The three extrinsic factors were GPs' attitudes and values towards screening, the conflict they experienced in offering screening information and the sense of powerlessness within the screening test process and the health care system generally. Extrinsic themes reveal GPs' attitudes and values to screening and to disability, as well as raising questions about the fundamental premise of testing. Conclusion The increasing availability and utilisation of screening tests, in particular first trimester tests, has expanded GPs' role in facilitating women's informed decision-making. Recognition of the importance of providing this complex information warrants longer consultations to respond to the time pressures that GPs experience. Understanding the intrinsic and extrinsic factors that impact on GPs may serve to shape educational resources to be more appropriate, relevant and supportive.

Abstract Background By providing information on the relative merits and potential harms of the options available and a framework to clarify preferences, decision aids can improve knowledge and realistic expectations and decrease decisional conflict in individuals facing decisions between alternative forms of action. Decision-making about prenatal testing for fetal abnormalities is often confusing and difficult for women and the effectiveness of decision aids in this field has not been established. This study aims to test whether a decision aid for prenatal testing of fetal abnormalities, when compared to a pamphlet, improves women's informed decision-making and decreases decisional conflict. Methods/design A cluster designed randomised controlled trial is being conducted in Victoria, Australia. Fifty General Practitioners (GPs) have been randomised to one of two arms: providing women with either a decision aid or a pamphlet. The two primary outcomes will be measured by comparing the difference in percentages of women identified as making an informed choice and the difference in mean decisional conflict scores between the two groups. Data will be collected from women using questionnaires at 14 weeks and 24 weeks gestation. The sample size of 159 women in both arms of the trial has been calculated to detect a difference of 18% (50 to 68%) in informed choice between the two groups. The required numbers have been adjusted to accommodate the cluster design, miscarriage and participant lost – to – follow up. Baseline characteristics of women will be summarised for both arms of the trial. Similarly, characteristics of GPs will be compared between arms. Differences in the primary outcomes will be analysed using 'intention-to-treat' principles. Appropriate regression techniques will adjust for the effects of clustering and include covariates to adjust for the stratifying variable and major potential confounding factors. Discussion The findings from this trial will make a significant contribution to improving women's experience of prenatal testing and will have application to a variety of maternity care settings. The evaluation of a tailored decision aid will also have implications for pregnancy care providers by identifying whether or not such a resource will support their role in providing prenatal testing information.

Abstract Background Early intervention teams attempt to improve outcome in schizophrenia through earlier detection and the provision of phase-specific treatments. Whilst the number of early intervention teams is growing, there is a lack of clarity over their essential structural and functional elements. Methods A 'Delphi' exercise was carried out to identify how far there was consensus on the essential elements of early intervention teams in a group of 21 UK expert clinicians. Using published guidelines, an initial list was constructed containing 151 elements from ten categories of team structure and function. Results Overall there was expert consensus on the importance of 136 (90%) of these elements. Of the items on which there was consensus, 106 (70.2%) were rated essential, meaning that in their absence the functioning of the team would be severely impaired. Conclusion This degree of consensus over essential elements suggests that it is reasonable to define a model for UK early intervention teams, from which a measure of fidelity could be derived.

Dental caries continues to be a public health issue, especially more evident in underserved populations throughout the U.S. Unfortunately, especially with an aging population, hundreds of thousands of resin composite restorations are replaced each year due to recurring decay and fracture. According to several cohort studies, the average life span of this type of restoration is 10 years or less, depending on the caries risk level of the patient and the complexity of the restorative procedure. Any new material development must depart from the simple restoration of form paradigm, in which the filling is simply inert/biocompatible. This review will discuss novel antibiofilm structures, based on a targeted approach specifically against dysbiotic bacteria. Biofilm coalescence can be prevented by using glycosyl transferase - GTF inhibitors, in a non-bactericidal approach. On the tooth substrate side, MMP-inhibiting molecules can improve the stability of the collagen in the hybrid layer. This review will also discuss the importance of testing the materials in a physiologically relevant environment, mimicking the conditions in the mouth in terms of mechanical loading, bacterial challenge, and the presence of saliva. Ultimately, the goal of materials development is to achieve durable restorations, capable of adapting to the oral environment and resisting challenges that go beyond mechanical demands. That way, we can prevent the unnecessary loss of additional tooth structure that comes with every re-treatment. CLINICAL SIGNIFICANCE: While proper restorative technique and patient education in terms of diet and oral hygiene are crucial factors in increasing the longevity of esthetic direct restorations, materials better able to resist and interact with the conditions of the oral environment are still needed. Reproducing the success of dental amalgams with esthetic materials continues to be the Holy Grail of materials development., Competing Interests: Declaration of Competing Interest The authors declare no conflict of interest., (Copyright © 2024 Elsevier Inc. All rights reserved.)

A goal of regenerative engineering is the rational design of materials to restore the structure-function relationships that drive reparative programs in damaged tissues. Despite the widespread use of extracellular matrices for engineering tissues, their application has been limited by a narrow range of tunable features. The primary objective of this study is to develop a versatile platform for evaluating tissue-specific cellular interactions using Type I collagen scaffolds with highly tunable biophysical properties. The kinetics of collagen fibrillogenesis were modulated through a combination of varied shear rate and pH during neutralization, to achieve a broad range of fibril anisotropy, porosity, diameter, and storage modulus. The role that each of these properties play in guiding muscle, bone, and vascular cell types was comprehensively identified, and informed the in vitro generation of three distinct musculoskeletal engineered constructs. Myogenesis was highly regulated by smaller fibrils and larger storage moduli, endothelial inflammatory phenotype was predominantly guided by fibril anisotropy, and osteogenesis was enhanced by highly porous collagen with larger fibrils. This study introduces a novel approach for dynamically modulating Type I collagen materials and provides a robust platform for investigating cell-material interactions, offering insights for the future rational design of tissue-specific regenerative biomaterials. STATEMENT OF SIGNIFICANCE: The biophysical properties of regenerative materials facilitate key cell-substrate interactions that can guide the morphology, phenotype, and biological response of cells. In this study, we describe the fabrication of an engineered collagen hydrogel that can be modified to exhibit control over a wide range of biophysical features, including fibril organization and size, nanoscale porosity, and mechanics. We identified the unique combination of collagen features that optimally promote regenerative muscle, bone, and vascular cell types while also delineating the properties that hinder these same cellular responses. This study presents a highly accessible method to control the biophysical properties of collagen hydrogels that can be adapted for a broad range of tissue engineering and regenerative applications., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.)

Purpose/Aim: Acrylamides are hydrolytically stable at pH lower than 2, and were shown to preserve bonded interface integrity with two-step, total etch adhesives. The objective of this study was to leverage those two characteristics in self-etching primers containing the acidic monomer 10-MDP and test the microtensile bond strength before and after incubation with S. mutans incubation. Materials and Methods: Acidic primers (10 wt % 10-methacryloyloxydecyl dihydrogen phosphate─10-MDP; 45 wt % N , N -diethyl-1,3-bis(acrylamido)propane─DEBAAP, or 2-hydroxyethyl methacrylate─HEMA; 45 wt %, glycerol-dimethacrylate─GDMA) and adhesives (DEBAAP or HEMA/10-MDP/UDMA 45/10/45 wt %) were made polymerizable by the addition of 0.2 wt % camphorquinone, 0.8 wt % ethyl-4-dimethylaminobenzoate, 0.4 wt % diphenyliodonium hexafluorophosphate, and 0.1 wt % butylhydroxytoluene. Nonsolvated materials were characterized for flexural strength (FS), modulus (E), toughness, water sorption/solubility (WS/SL), contact angle, and vinyl conversion (DC). Viscosity was evaluated after adding 20 and 40 vol % ethanol to the primer and adhesive, respectively. The experimental materials or Clearfil SE Bond (CC─commercial control) were used to bond a commercial composite (Filtek Supreme) to the flat surface of human dentin. Microtensile bond strength (MTBS) was tested in 1 mm 2 sticks for the 5 primer/bond combinations: CC (Clearfil Bond Primer and Bond), HH (HEMA/HEMA), DD (DEBAAP/DEBAAP), HD (HEMA/DEBAAP), and DH (DEBAAP/HEMA). Prior to testing, sticks were stored in water or biofilm-inducing culture medium with S. mutans for 1 week. Confocal images and FTIR-ATR evaluation evaluated the hybrid layer of the adhesives. Results were analyzed using Student's t -test (WS, SL, DC, contact angle, FS, E, toughness), one-way ANOVA/Tukey's test for viscosity, and two-way ANOVA/Tukey's test for MTBS (95%). Results: HEMA-based materials had lower contact angle ( p = 0.004), higher WS ( p < 0.001), and similar SL values compared to DEBAAP ( p = 0.126). FS ( p = 0.171) and E ( p = 0.065) dry values were similar, but after one week of water storage, FS/E dropped more significantly for HEMA materials. Dry and wet toughness was greater for DEBAAP ( p < 0.001), but it also had the greatest drop (46%). Clearfil bonds had the highest viscosity, followed by DEBAAP and HEMA, respectively ( p = 0.002). For the primers, HEMA had the lowest viscosity ( p = 0.003). As far as MTBS, all groups tested in water were statistically different when compared with HH ( p < 0.001). After storage in biofilm, DH had the highest MTBS value, being statistically different from HH ( p = 0.002), CC ( p = 0.015), and DD ( p = 0.027). Conclusions: The addition of a diacrylamide and its association with HEMA in self-etching adhesive systems provided greater bonding stability after bacterial challenge.

Streptococcus mutans is the primary oral caries-forming bacteria, adept at producing "sticky" biofilms via the synthesis of insoluble extracellular polysaccharides (EPS), catalyzed by glucosyltransferases (GTFs). To circumvent the use of broad-spectrum antibiotics to combat these bacteria, this study sought to modify existing EPS-targeting small molecules with the ultimate goal of producing anti-biofilm polymer surfaces specifically targeting S. mutans. To achieve this, a known GTF inhibitor (G43) was modified with methoxy or tetraethyleneglycol substitutions in different positions (nine derivatives, tested at 50-µM) to pinpoint potential sites for future methacrylate functionalization, and then assessed against single-species S. mutans biofilms. As expected, the compounds did not diminish the bacterial viability. In general, the compounds with methoxy substitution were not effective in reducing EPS formation, whereas the tetraethyleneglycol substitution (G43-C3-TEG) led to a decrease in the concentration of insoluble EPS, although the effect is less pronounced than for the parent G43. This aligns with the reduced GTF-C activity observed at different concentrations of G43-C3-TEG, as well as the consequent decrease in EPS formation, and notable structural changes. In summary, this study determined that G43-C3-TEG is non-bactericidal and can selectively reduce the biofilm formation, by decreasing the production of EPS. This molecule will serve to functionalize surfaces of materials to be tested in future research., (© 2023. The Author(s).)

In this study, an acrylamide-based adhesive was combined with a thiourethane-based composite to improve bond stability and reduce polymerization stress, respectively, of simulated composite restorations. The stability testing was conducted under physiologic conditions, combining mechanical and bacterial challenges. Urethane dimethacrylate was combined with a newly synthesized triacrylamide (TMAAEA) or HEMA (2-hydroxyethyl-methacrylate; control) to produce a 2-step total-etch adhesive system. Methacrylate-based composites (70 wt% silanized filler) were formulated, containing thiourethane oligomers at 0 (control) or 20 wt%. Standardized preparations in human third molars were restored; then, epoxy replicas were obtained from the occlusal surfaces before and after 7-d storage in water or with Streptococcus mutans biofilm, which was tested after storage in an incubator (static) or the bioreactor (mechanical challenge). Images were obtained from the replicas (scanning electron microscopy) and cross sections of the samples (confocal laser scanning microscopy) and then analyzed to obtain measurements of gap, bacterial infiltration, and demineralization. Microtensile bond strength of specimens stored in water or biofilm was assessed in 1-mm 2 stick specimens. Data were analyzed with analysis of variance and Tukey's test (α = 0.05). HEMA-based materials had greater initial gap measurements, indicating more efficient bonding for the acrylamide materials. When tested in water, the triacrylamide-based adhesive had smaller gaps in the incubator or bioreactor. In the presence of biofilm, there was less difference among materials, but the acrylamide/thiourethane combination led to statistically lower gap formation in the bioreactor. HEMA and TMAAEA-based adhesives produced statistically similar microtensile bond strengths after being stored in water for 7 d, but after the same period with biofilm-challenged specimens, the TMAAEA-based adhesives were the only ones to retain the initial bond strength values. The use of a stable multiacrylamide-based adhesive led to the preservation of the resin-dentin bonded interface after a physiologically relevant challenge. Future studies will include a multispecies biofilm model.

Tinnitus is the sensation of hearing a sound in the absence of an internal or external source and is a common problem encountered in primary care. Most cases of tinnitus are benign and idiopathic and are strongly associated with sensorineural hearing loss. A standard workup begins with a targeted history and physical examination to identify treatable causes and associated symptoms that may improve with treatment. Less common but potentially dangerous causes such as vascular tumors and vestibular schwannoma should be ruled out. A comprehensive audiologic evaluation should be performed for patients who experience unilateral tinnitus, tinnitus that has been present for six months or longer, or that is accompanied by hearing problems. Neuroimaging is not part of the standard workup unless the tinnitus is asymmetric or unilateral, pulsatile, associated with focal neurologic abnormalities, or associated with asymmetric hearing loss. Cognitive behavior therapy is the only treatment that has been shown to improve quality of life in patients with tinnitus. Sound therapy and tinnitus retraining therapy are treatment options, but evidence is inconclusive. Melatonin, antidepressants, and cognitive training may help with sleep disturbance, mood disorders, and cognitive impairments, respectively. Avoidance of noise exposure may help prevent the development or progression of tinnitus. Providing information about the natural progression of tinnitus and being familiar with the causes that warrant additional evaluation, imaging, and specialist involvement are essential to comprehensive care.

The incorporation of thiourethane prepolymer (TU) into either the organic phase or as a surface treatment for filler particles in composites reduces polymerization stress and improves fracture toughness. The aim of this study was to gain insight into the influence of the inclusion of thiourethanes on the resulting network of methacrylate-based materials polymerized via free-radical mechanisms. Dynamic mechanical analysis was used to elucidate network parameters and potential stress relaxation behavior of these networks. TU oligomers were synthesized using a combination of trimethylol-tris-3-mercaptopropionate and dicyclohexylmethane 4,4'-diisocyanate and added into composite formulations at 20 wt% replacing part of the organic matrix and/or as TU-silanes used to functionalize filler particles (TU-matrix, TU-Sil or TU-matrix/sil). Materials not containing any form of TU were used as the control (in those cases, 3-(trimethoxysilyl)propyl methacrylate was used as the silane agent). Filler was added at 50 wt%. Degree of conversion was evaluated by near-IR spectroscopy, mechanical properties by 3-point bending and rotational rheometry. Dynamic mechanical analysis was used to obtain network parameters (glass transition temperature (T g ), storage modulus, cross-link density, and breadth of tan delta a proxy for network homogeneity - temperature sweep experiments) and to evaluate the potential for network relaxation (stress relaxation). TU-containing formulations showed 10% higher DC than the control. The time to reach storage/loss modulus crossover in the rheometer experiments was significantly longer for TU-matrix and TU-matrix/sil in comparison with the control (21.6, 27.9, and 5.1 s, respectively). TU-matrix and TU-matrix/sil presented significant lower T g than the control (151.5, 153.8, and 161.3 °C, respectively). There were no statistical differences among the groups in terms of shear modulus, cross-link density, breadth of tan delta, flexural strength/modulus, and toughness. For at least one group (TU-matrix/sil), the relaxation time was four times faster than for the control at 105 °C. The addition of TU additives into dental polymers resulted in a stark reduction in the stress relaxation time. This behavior, in tandem with the network characterization and mechanical properties seems to indicate the TU networks undergo a variety of reversible associative and dissociative chemical reactions which facilitate enhanced stress relief.

Introduction of thiourethane (TU) oligomer to resin-based dental restorative materials reduces stress and improves fracture toughness without compromising conversion. Localization of TU at the resin-filler interface via silanization procedures may lead to more substantial stress reduction and clinical property enhancements. The objective of this study was to evaluate composite properties as a function of TU-functionalized filler concentration. TU oligomers were synthesized using click-chemistry techniques and subsequently silanized to barium glass filler. Resin-based composites were formulated using varying ratios of TU-functionalized filler and conventional methacrylate-silanized barium filler. Material property testing included thermogravimetric analysis, real-time polymerization kinetics and depth of cure, polymerization stress, stress relaxation and fracture toughness. Clinical property testing included water sorption/solubility, composite paste viscosity, and gloss and surface roughness measured before and after subjecting the samples to 6 h of continuous tooth brushing in a custom-built apparatus using a toothpaste/water mixture. Increasing TU-filler in the composite resulted in as much as a 78% reduction in stress, coupled with an increase in fracture toughness. Conversion was similar for all groups. After simulated tooth brushing, gloss reduction was lower for TU-containing composites and surface roughness was less than or equal to the control., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Objectives: The aim of this study was to modify the surface of fillers used in dental composites by the synthesis of two novel thiourethane oligomeric silanes, used to functionalize the silica-containing inorganic particles. Several thiourethane silane concentrations were tested during the silanization process to systematically assess the effect of silane coverage on experimental composite conversion, polymerization stress and fracture toughness., Materials and Methods: Two different thiourethane silanes were synthesized based either on 1,6-hexanediol-diissocynate (HDDI), or 1,3-bis(1-isocyanato-1-methylethyl) benzene (BDI). Conventional 3-(Trimethoxysilyl)propyl methacrylate was used as the control. Glass fillers were silanized with 1, 2 or 4 wt% of each thiourethane silane, then evaluated by thermogravimetrical analysis. Photopolymerizable resin composites were prepared with Bis-GMA/UDMA/TEGDMA and 50 wt% silanized glass filler. Polymerization kinetics and degree of conversion were tested using Near-IR. Bioman was used to test polymerization stress. Data were analyzed with two-way ANOVA/Tukey's test (α = 5%)., Results: The mass of silane coupled to the filler increased with the concentrations of thiourethane in the silanizing solution, as expected. Thiourethane-containing groups exhibited significantly higher degree of conversion compared to control groups, except for BDI 4%. HDDI 4%, BDI 2% and BDI 4% showed significantly lower polymerization stress than control groups. HDDI 4% exhibited significantly higher fracture toughness., Conclusions and Clinical Significance: Novel filler functionalization with thiourethane silanes may be a promising alternative for improving dental composites properties by significantly increasing the degree of conversion, fracture toughness and reducing the polymerization stress., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Background: Spontaneous coronary artery dissection (SCAD) occurs when an epicardial coronary artery is narrowed or occluded by an intramural hematoma. SCAD mainly affects women and is associated with pregnancy and systemic arteriopathies, particularly fibromuscular dysplasia. Variants in several genes, such as those causing connective tissue disorders, have been implicated; however, the genetic architecture is poorly understood. Here, we aim to better understand the diagnostic yield of rare variant genetic testing among a cohort of SCAD survivors and to identify genes or gene sets that have a significant enrichment of rare variants., Methods: We sequenced a cohort of 384 SCAD survivors from the United Kingdom, alongside 13 722 UK Biobank controls and a validation cohort of 92 SCAD survivors. We performed a research diagnostic screen for pathogenic variants and exome-wide and gene-set rare variant collapsing analyses., Results: The majority of patients within both cohorts are female, 29% of the study cohort and 14% validation cohort have a remote arteriopathy. Four cases across the 2 cohorts had a diagnosed connective tissue disorder. We identified pathogenic or likely pathogenic variants in 7 genes ( PKD1 , COL3A1 , SMAD3 , TGFB2 , LOX , MYLK , and YY1AP1 ) in 14/384 cases in the study cohort and in 1/92 cases in the validation cohort. In our rare variant collapsing analysis, PKD1 was the highest-ranked gene, and several functionally plausible genes were enriched for rare variants, although no gene achieved study-wide statistical significance. Gene-set enrichment analysis suggested a role for additional genes involved in renal function., Conclusions: By studying the largest sequenced cohort of SCAD survivors, we demonstrate that, based on current knowledge, only a small proportion have a pathogenic variant that could explain their disease. Our findings strengthen the overlap between SCAD and renal and connective tissue disorders, and we highlight several new genes for future validation.

Cytosine methylation is an ancient epigenetic modification yet its function and extent within genomes is highly variable across eukaryotes. In mammals, methylation controls transposable elements and regulates the promoters of genes. In insects, DNA methylation is generally restricted to a small subset of transcribed genes, with both intergenic regions and transposable elements (TEs) depleted of methylation. The evolutionary origin and the function of these methylation patterns are poorly understood. Here we characterise the evolution of DNA methylation across the arthropod phylum. While the common ancestor of the arthropods had low levels of TE methylation and did not methylate promoters, both of these functions have evolved independently in centipedes and mealybugs. In contrast, methylation of the exons of a subset of transcribed genes is ancestral and widely conserved across the phylum, but has been lost in specific lineages. A similar set of genes is methylated in all species that retained exon-enriched methylation. We show that these genes have characteristic patterns of expression correlating to broad transcription initiation sites and well-positioned nucleosomes, providing new insights into potential mechanisms driving methylation patterns over hundreds of millions of years., Competing Interests: The authors have declared that no competing interests exist.

Objectives: Thiourethane oligomers have been shown to increase the fracture toughness and reduce the polymerization stress of methacrylate-based materials. However, network formation has not been elucidated in these materials yet. The aim of this study was to evaluate how the addition of a thiourethane oligomer (TU) influences the sol/gel composition and network structure of methacrylate-based materials using dynamic mechanical analysis and extraction methods., Materials and Methods: BisGMA/TEGDMA at systematically varied mass ratios (20/80 to 80/20wt%) were mixed with pre-polymerized thiourethane oligomers at 0 (control) or 20wt%, synthesized by combining pentaerythritol tetra-3-mercaptopropionate with dicyclohexylmethane 4,4⿲-Diisocyanate, at 1:2 isocyanate:thiol. 0.1wt% of 2,2-Dimethoxy-2-phenylacetophenone was added as the photoinitiator and 0.3wt% of 2,6-di-tert-butyl-4-methylphenol was added as a free radical inhibitor. Disk specimens (0.8ÿ10mm in diameter, n=3) were photoactivated at 270mW/ (320⿿500nm) for 1min. The degree of conversion (DC) was measured in near-IR (˿6165cm ⿿1 ). Specimens were immersed in two different solvents (water for 7 days or dicholoromethane for 48h). Water sorption (WS) and solubility (SL) were obtained according to ISO 4049. The leachates for both solutions were analyzed with 1 H-NMR (400MHz, CDCL 3 ). Bar specimens (1ÿ3ÿ25mm, photocured and then post-processed at 180°C for 8h to DC>95%) were subjected to dynamic mechanical analysis (⿿30 to 230°C) to obtain glass transition temperature (Tg), tan delta curves and crosslinking density (ν). Data was analyzed with two-way ANOVA/Tukey⿿s test (95%)., Results: In general, the presence of TU increased the overall conversion. The WS was similar for all groups, but the SL decreased by 2-fold with the addition of the TU oligomer for all compositions, except BisGMA/TEGDMA 80/20. The BisGMA concentration of the leachates increased with increasing BisGMA in the initial mixture, and with the presence of thiourethane. This compositional drift of the gel with the presence of TU was attributed to the preferential dissolution of TEGDMA into the TU network. Tg and ν decreased with the addition of TU, as expected. The addition of TU produced more homogeneous networks, as evidenced by narrower breadth of the tan delta curve., Conclusion: The addition of TU affected the composition of the sol/gel in crosslinked networks, which were more homogeneous and presented 2-fold less potentially toxic leachates than the methacrylate controls., Clinical Significance: The addition of TU may produce less cytotoxic materials based on the increased conversion and reduced amount of unreacted extractables from its network after water storage., (Copyright © 2019 The Academy of Dental Materials. Published by Elsevier Inc. All rights reserved.)

In animals, small RNA molecules termed PIWI-interacting RNAs (piRNAs) silence transposable elements (TEs), protecting the germline from genomic instability and mutation. piRNAs have been detected in the soma in a few animals, but these are believed to be specific adaptations of individual species. Here, we report that somatic piRNAs were probably present in the ancestral arthropod more than 500 million years ago. Analysis of 20 species across the arthropod phylum suggests that somatic piRNAs targeting TEs and messenger RNAs are common among arthropods. The presence of an RNA-dependent RNA polymerase in chelicerates (horseshoe crabs, spiders and scorpions) suggests that arthropods originally used a plant-like RNA interference mechanism to silence TEs. Our results call into question the view that the ancestral role of the piRNA pathway was to protect the germline and demonstrate that small RNA silencing pathways have been repurposed for both somatic and germline functions throughout arthropod evolution.

Objective: To assess the influence of hydrophilicity of reactive nanogels on the mechanical performance of dental adhesives and microtensile bond strength (μTBS) to dentin after 24h or 3 months of aging., Methods: A series of three nanogels were synthesized: NG1-IBMA/UDMA; NG2-HEMA/BisGMA; NG3-HEMA/TE-EGDMA. The nanogels were dispersed in solvent, HEMA or BisGMA/HEMA. The degree of conversion (DC) of the materials was measured and the flexural modulus of these polymers was evaluated in dry or wet conditions. For μTBS analysis, a model adhesive was used without nanogel (control) or with the incorporation of nanogels. μTBS was evaluated after storage in distilled water for 24h or 3 months. The analysis of the fracture was performed after μTBS testing. Data were analyzed using ANOVA and Tukey's test (α=0.05)., Results: Water significantly increased the modulus of NG1 and NG2 dispersed in solvent, while significantly decreased the stiffness of NG3. All polymers dispersed in HEMA and BisGMA/HEMA had significantly lower modulus when stored in water. NG2 showed the highest DC in solvent and BisGMA/HEMA. In HEMA, NG1 and NG3 produced the highest DC. After three months, NG2 showed the best μTBS. The μTBS of NG2-containing adhesive resin significantly increased after 3 months, while storage had no effect in the control group, NG1 and NG3., Significance: The more hydrophobic IBMA/UDMA nanogel showed higher bulk material mechanical property results, but the best dentin bond strength values, and notably strength values that improved upon storage, were obtained with the amphiphilic nanogel based on BisGMA/HEMA., (Copyright © 2016 The Academy of Dental Materials. Published by Elsevier Ltd. All rights reserved.)

Argonaute2 (Ago2) is a rapidly evolving nuclease in the Drosophila melanogaster RNA interference (RNAi) pathway that targets viruses and transposable elements in somatic tissues. Here we reconstruct the history of Ago2 duplications across the D. obscura group and use patterns of gene expression to infer new functional specialization. We show that some duplications are old, shared by the entire species group, and that losses may be common, including previously undetected losses in the lineage leading to D. pseudoobscura We find that while the original (syntenic) gene copy has generally retained the ancestral ubiquitous expression pattern, most of the novel Ago2 paralogs have independently specialized to testis-specific expression. Using population genetic analyses, we show that most testis-specific paralogs have significantly lower genetic diversity than the genome-wide average. This suggests recent positive selection in three different species, and model-based analyses provide strong evidence of recent hard selective sweeps in or near four of the six D. pseudoobscura Ago2 paralogs. We speculate that the repeated evolution of testis specificity in obscura group Ago2 genes, combined with their dynamic turnover and strong signatures of adaptive evolution, may be associated with highly derived roles in the suppression of transposable elements or meiotic drive. Our study highlights the lability of RNAi pathways, even within well-studied groups such as Drosophila, and suggests that strong selection may act quickly after duplication in RNAi pathways, potentially giving rise to new and unknown RNAi functions in nonmodel species., (Copyright © 2016 by the Genetics Society of America.)

Drosophila melanogaster is an important laboratory model for studies of antiviral immunity in invertebrates, and Drosophila species provide a valuable system to study virus host range and host switching. Here, we use metagenomic RNA sequencing of about 1600 adult flies to discover 25 new RNA viruses associated with six different drosophilid hosts in the wild. We also provide a comprehensive listing of viruses previously reported from the Drosophilidae. The new viruses include Iflaviruses, Rhabdoviruses, Nodaviruses, and Reoviruses, and members of unclassified lineages distantly related to Negeviruses, Sobemoviruses, Poleroviruses, Flaviviridae, and Tombusviridae. Among these are close relatives of Drosophila X virus and Flock House virus, which we find in association with wild Drosophila immigrans. These two viruses are widely used in experimental studies but have not been previously reported to naturally infect Drosophila. Although we detect no new DNA viruses, in D. immigrans and Drosophila obscura, we identify sequences very closely related to Armadillidium vulgare iridescent virus (Invertebrate iridescent virus 31), bringing the total number of DNA viruses found in the Drosophilidae to three.