Analysis of Financial Barriers Experienced by Prospective Genetic Counseling Students.

PURPOSE: High costs of applying to genetic counseling graduate programs (GCGPs) are likely a barrier to workforce diversification. We sought to determine application costs and assess differences between individuals of historically underrepresented racial and ethnic backgrounds in medicine (hURM) and non-hURM applicants. METHODS: Applicants to GCGPs between 2005-2020 were surveyed about application history, related expenses, volunteer hours, and financial resources; 383 responses were analyzed. RESULTS: Median total application costs (MTAC) were $2,634, $4,762, and $5,607 (one, two, and three or more application cycles, respectively). Interview-related items (which includes travel) had the highest median cost (one application cycle: $879). Among those who applied to multiple cycles, hURM respondents had higher MTAC than those of non-hURM ($6,713 versus $4,762, p=0.03) and lower median total volunteer hours (246 versus 381, p=0.03). Parental education level differed by hURM status (p=0.04). Median financial contribution from parents with and without advanced degrees varied significantly (60% vs 2%, p=0.0009). CONCLUSION: Significant costs are incurred during the GCGP application process, but notable differences in costs and resources were observed between hURM and non-hURM applicants. Stakeholders within the profession should implement strategies to reduce financial barriers and the resulting inequities in the application process.

Decision-Making Time Cells in Hippocampal Dorsal CA1.

Sequential neural dynamics encoded by "time cells" play a crucial role in hippocampal function. However, the role of hippocampal sequential neural dynamics in associative learning is an open question. In this manuscript, we used two-photon Ca2+ imaging of dorsal CA1 pyramidal neurons in head-fixed mice performing a go-no-go associative learning task. We found that pyramidal cells responded differentially to the rewarded or unrewarded stimuli. The stimuli were decoded accurately from the activity of the neuronal ensemble, and accuracy increased substantially as the animal learned to differentiate the stimuli. Decoding the stimulus from individual pyramidal cells that responded differentially revealed that decision-making took place at discrete times after stimulus presentation. Lick prediction decoded from the ensemble activity of cells in dCA1 correlated linearly with lick behavior indicating that sequential activity of pyramidal cells in dCA1 constitutes a temporal memory map used for decision-making in associative learning.

Physical Properties and Clinical Performance of Short Fiber Reinforced Resin-based Composite in Posterior Dentition: Systematic Review and Meta-analysis.

OBJECTIVE: This study compares the physical properties and clinical performance of short fiber reinforced composites (SFRC) to those of particulate-filled resin-based composites (PFRC) for class I and II direct restorations in permanent dentition. METHODS: Systematic review and meta-analysis was conducted using PubMed, Embase (Elsevier), and Dentistry and Oral Sciences Source (EBSCO) databases. The outcomes evaluated were physical properties including flexural strength, flexural modulus, elastic modulus, microhardness, shrinkage, fracture toughness, degree of conversion, and depth of cure. Clinical performance was evaluated with a systematic review. RESULTS: The meta-analyses favored SFRC for flexural strength and fracture toughness compared to every PFRC subgroup, with a high quality of evidence. For all other properties, the meta-analyses favored SFRC to overall PFRC, with some non-significant differences with certain PFRC subgroups. The most recent clinical trial showed SFRC performed similarly to PFRC, however older studies suggest inferior surface texture and discoloration of SFRC compared to PFRC. CONCLUSION: This study can aid dental professionals in clinical decision making, supporting that SFRC offers improved physical properties, especially fracture resistance and flexural strength, compared to PFRC.

FOxTROT2: innovative trial design to evaluate the role of neoadjuvant chemotherapy for treating locally advanced colon cancer in older adults or those with frailty.

Treating older adults with cancer is increasingly important in modern oncology practice. However, we currently lack the high-quality evidence needed to guide optimal management of this heterogeneous group. Principally, historic under-recruitment of older adults to clinical trials limits our understanding of how existing evidence can be applied to this group. Such uncertainty is particularly prevalent in the management of colon cancer (CC). With CC being most common in older adults, many patients also suffer from frailty, which is recognised as being strongly associated with poor clinical outcomes. Conducting clinical trials in older adults presents several major challenges, many of which impact the clinical relevance of results to a real-world population. When considering this heterogeneous group, it may be difficult to define the target population, recruit participants effectively, choose an appropriate trial design, and ensure participants remain engaged with the trial during follow-up. Furthermore, after overcoming these challenges, clinical trials tend to enrol highly selected patient cohorts that comprise only the fittest older patients, which are not representative of the wider population. FOxTROT1 was the first phase III randomised controlled trial to illustrate the benefit of neoadjuvant chemotherapy (NAC) in the treatment of CC. Patients receiving NAC had greater 2-year disease-free survival compared to those proceeding straight to surgery. Outcomes for older adults in FOxTROT1 were similarly impressive when compared to their younger counterparts. Yet, this group inevitably represents a fitter subgroup of the older patient population. FOxTROT2 has been designed to investigate NAC in a full range of older adults with CC, including those with frailty. In this review, we describe the key challenges to conducting a robust clinical trial in this heterogeneous patient group, highlight our strategies for overcoming these challenges in FOxTROT2, and explain how we hope to provide clarity on the optimal treatment of CC in older adults.

The Influence of Distance on Radiant Exposure and Degree of Conversion Using Different Light-Emitting-Diode Curing Units.

OBJECTIVES: To investigate the influence of curing distance on the degree of conversion (DC) of a resin-based composite (RBC) when similar radiant exposure was achieved using six different light-curing units (LCUs) and to explore the correlation among irradiance, radiant exposure, and DC. METHODS AND MATERIALS: A managing accurate resin curing-resin calibrator system was used to collect irradiance data for both top and bottom specimen surfaces with a curing distance of 2 mm and 8 mm while targeting a consistent top surface radiant exposure. Square nanohybrid-dual-photoinitiator RBC specimens (5 × 5 × 2 mm) were cured at each distance (n=6/LCU/distance). Irradiance and DC (micro-Raman spectroscopy) were determined for the top and bottom surfaces. The effect of distance and LCU on irradiance, radiant exposure, and DC as well as their linear associations were analyzed using analysis of variance and Pearson correlation coefficients, respectively (α=0.05). RESULTS: While maintaining a similar radiant exposure, each LCU exhibited distinctive patterns in decreased irradiance and increased curing time. No significant differences in DC values (63.21%-70.28%) were observed between the 2- and 8-mm distances, except for a multiple-emission peak LCU. Significant differences in DC were detected among the LCUs. As expected, irradiance and radiant exposure were significantly lower on the bottom surfaces. However, a strong correlation between irradiance and radiant exposure did not necessarily result in a strong correlation with DC. CONCLUSIONS: The RBC exhibited DC values >63% when the top surface radiant exposure was maintained, although the same values were not reached for all lights. A moderate-strong correlation existed among irradiance, radiant exposure, and DC.

Comparison of Internal Adaptation of Bulk-fill and Increment-fill Resin Composite Materials.

OBJECTIVES:: To evaluate 1) the internal adaptation of a light-activated incremental-fill and bulk-fill resin-based composite (RBC) materials by measuring the gap between the restorative material and the tooth structure and 2) the aging effect on internal adaptation. METHODS AND MATERIALS:: Seventy teeth with class I cavity preparations were randomly distributed into five groups; four groups were restored with bulk-fill RBCs: Tetric EvoCeram Bulk Fill (TEC), SonicFill (SF), QuiXX Posterior Restorative (QX), and X-tra fil (XF); the fifth group was restored with incremental-fill Filtek Supreme Ultra Universal Restorative (FSU). One-half of the specimens of each group were thermocycled. Each tooth was sectioned, digital images were recorded, and the dimensions of any existing gaps were measured. Data were analyzed using analysis of variance (α=0.05). RESULTS:: FSU had the smallest gap measurement values compared with the bulk-fill materials except QX and TEC ( p≤0.008). FSU had the smallest sum of all gap category values compared with the bulk-fill materials, except QX ( p≤0.021). The highest gap incidence and size values were found at the composite/adhesive interface. All aged groups had greater gap values in regard to the gap measurement and the sum of all gap categories compared with non-aged groups. SIGNIFICANCE:: The incrementally placed material FSU had the highest internal adaptation to the cavity surface, while the four bulk-fill materials showed varied results. Thermocycling influenced the existing gap area magnitudes. The findings suggest that the incremental-fill technique produces better internal adaptation than the bulk-fill technique.

Durable targeting of B-lymphocytes in living mice.

Transfer to and enduring expression of genes in B cells has proved a vexing challenge. We report here a novel method for the specific and durable targeting of B lymphocytes in living mice. The method involves generation of lentiviruses pseudotyped with an anti-CD19 antibody. CD19 targeting viruses injected in the spleen of living mice efficiently transduced B cells and plasma cells detected by flow cytometry analysis of GFP expression. Expression of the reporter gene could be detected in the intact animal by external imaging for more than a year and was enhanced by booster immunization. Our method thus enables the specific delivery, expression and localization by external imaging of exogenous genes to the B cells and plasma cells of living individuals.

The effects of multiple anaesthetic episodes on equine recovery quality.

BACKGROUND: Although rare, 70% of equine fatalities during recovery from general anaesthesia (GA) are due to catastrophic fractures from poor recovery quality. OBJECTIVE: To determine the effect of repeated GA recovery on GA recovery quality. STUDY DESIGN: Experimental blinded trial. METHODS: Eight adult horses underwent six GA events on sevoflurane for distal limb MRI examination over a 14-week period. Prior to GA recovery, xylazine was administered. Randomly ordered video-recorded GA recoveries were scored by three blinded board certified veterinary anaesthesiologists, unaware of patient identity or GA event number, for nine parameters using a 100 mm visual analogue scale (VAS) where 0 = worst and 100 = best. The number of attempts to stand, duration of lateral and sternal recumbency, total recovery duration and physiologic parameters during each GA event were recorded. Repeated measures ANOVA were used to detect differences. Agreement between observer VAS scores was determined via inter-rater reliability using an intraclass correlation. RESULTS: With GA recovery experience, VAS scores for balance and coordination, knuckling, and overall quality of recovery were improved and the duration of lateral recumbency was increased. There were no differences in total recovery duration, number of attempts to stand, physiologic parameters other than heart rate during GA, or VAS scores for activity in lateral recumbency, move to sternal, move to stand, or strength. MAIN LIMITATIONS: Each GA event was relatively short and there was no surgical stimulation. The same results may not occur if there was surgical stimulation and pain during each GA event. CONCLUSION: Recovery from GA improves with multiple anaesthetic episodes in horses. Clinicians can advise clients that horses are likely to have better GA recovery on repeated GA recovery due to improved balance and coordination and reduced knuckling. Additionally, there is no change in anaesthetic morbidity with six repeated GA events over a 14-week period.

Cuspal Deflection in Premolar Teeth Restored with Bulk-Fill Resin-Based Composite Materials.

The present study investigated the effect of three high-viscosity bulk-fill resin-based composite materials on cuspal deflection in natural teeth. Thirty-two sound maxillary premolar teeth with large slot mesio-occlusal-distal cavities were distributed into four groups (n=8). Three groups were restored with bulk-fill resin composite materials (Tetric EvoCeram Bulk Fill, Ivoclar Vivadent, Schaan, Liechtenstein; x-tra fil, VOCO, Cuxhaven, Germany; and SonicFill, Kerr, Orange, CA, USA) in a single 4-mm increment. The conventional composite group, Filtek Z100 (3M ESPE, St Paul, MN, USA), was used to restore the cavities in 2-mm increments. Cusp deflection was recorded postirradiation using a Nikon measurescope UM-2 (Nikon, Tokyo, Japan) by measuring the changes in the bucco-palatal widths of the teeth at five minutes, 24 hours, and 48 hours after completion of the restorations. Cuspal deflection was significantly higher in the conventional composite than in the Tetric EvoCeram Bulk Fill ( p=0.0031), x-tra fil ( p=0.0029), and SonicFill Bulk ( p=0.0002) groups. There were no significant differences in cuspal deflection among the three bulk-fill materials (all p<0.05). In conclusion, all the investigated bulk-fill resin composites exhibited cuspal deflection values that were smaller than those associated with a conventional incrementally placed resin composite.

Achievement of Sustained Net Plasma Heating in a Fusion Experiment with the Optometrist Algorithm.

Many fields of basic and applied science require efficiently exploring complex systems with high dimensionality. An example of such a challenge is optimising the performance of plasma fusion experiments. The highly-nonlinear and temporally-varying interaction between the plasma, its environment and external controls presents a considerable complexity in these experiments. A further difficulty arises from the fact that there is no single objective metric that fully captures both plasma quality and equipment constraints. To efficiently optimise the system, we develop the Optometrist Algorithm, a stochastic perturbation method combined with human choice. Analogous to getting an eyeglass prescription, the Optometrist Algorithm confronts a human operator with two alternative experimental settings and associated outcomes. A human operator then chooses which experiment produces subjectively better results. This innovative technique led to the discovery of an unexpected record confinement regime with positive net heating power in a field-reversed configuration plasma, characterised by a >50% reduction in the energy loss rate and concomitant increase in ion temperature and total plasma energy.

A qualitative exploration of the informed consent process in hematopoietic cell transplantation clinical research and opportunities for improvement.

Informed consent (IC) struggles to meet the ethical principles it strives to embody in the context of hematopoietic cell transplantation (HCT). Patients often participate in multiple clinical trials making it difficult to effectively inform the participants and fulfill complex regulations. The recent Notice of Proposed Rule Making would make major changes to federal requirements, providing a timely opportunity to evaluate existing practice. Twenty health care professionals within a Midwest Academic Medical Center involved in obtaining IC in the HCT clinic or involved in patient care during or after the IC process were interviewed to understand: (1) how they approached the IC process; (2) how they described a 'successful' IC process; and (3) opportunities for innovation. Narrative and discourse analyses of interviews indicate that providers understand IC to be a collaborative process requiring engagement and participation of providers, patients and caregivers. 'Markers of success' were identified including cognitive, affective and procedural markers focusing on patient understanding and comfort with the decision to participate. Opportunities for innovating the process included use of decision aids and tablet-based technology, and better use of patient portals. Our findings suggest specific interventions for the IC process that could support the process of consent for providers, patients and caregivers.

Effect of triple antibiotic paste with or without ethylenediaminetetraacetic acid on surface loss and surface roughness of radicular dentine.

This study aimed to compare the effect of two concentrations of triple antibiotic paste (TAP) with or without ethylenediaminetetraacetic acid (EDTA) on surface loss and surface roughness of radicular dentine. Human radicular dentine specimens were randomized into six experimental groups (n = 16 per group). The first and second groups were treated with 1,000 mg/mL or 1 mg/mL of TAP for 4 weeks. The third and fourth groups were treated with 1,000 mg/mL or 1 mg/mL of TAP for 4 weeks followed by 17 % EDTA for 5 min. The fifth group was treated with 17 % EDTA for 5 min and the sixth group received no treatment (control). Dentine surface loss and surface roughness were quantified after various treatments using optical and contact profilometry, respectively. One-way ANOVA followed by Fisher's protected least significant differences was used for statistical analyses. All treatment groups showed significantly higher surface loss compared to the untreated dentine. Dentine treated with 1,000 mg/mL had significant increase in surface loss and surface roughness compared to dentine treated with 1 mg/mL of TAP. The use of EDTA after both concentrations of TAP did not have significant additive effect on surface loss and surface roughness of dentine. The clinically used concentration of TAP (1,000 mg/mL) caused significantly higher surface loss and surface roughness of radicular dentine compared to the use of 1 mg/mL of TAP. Furthermore, the substantial amount of dentine surface loss and surface roughness detected in the current study may be attributed to TAP rather than EDTA.

Effect of Base and Inlay Restorative Material on the Stress Distribution and Fracture Resistance of Weakened Premolars.

The purpose of this study was to evaluate the influence of direct base and indirect inlay materials on stress distribution and fracture resistance of endodontically treated premolars with weakened cusps. Forty healthy human premolars were selected; five were left intact as controls (group C+), and the others were subjected to endodontic treatment and removal of buccal and lingual cusp dentin. Five teeth were left as negative controls (group C-). The remaining 30 teeth were divided into two groups according to the direct base material (glass ionomer [GIC] or composite resin [CR]). After base placement, each group was subjected to extensive inlay preparation, and then three subgroups were created (n=5): no inlay restoration (GIC and CR), restored with an indirect composite resin inlay (GIC+IR and CR+IR), and restored with a ceramic inlay (GIC+C and CR+C). Each specimen was loaded until fracture in a universal testing machine. For finite element analysis, the results showed that the removal of tooth structure significantly affected fracture resistance. The lowest values were presented by the negative control group, followed by the restored and based groups (not statistically different from each other) and all lower than the positive control group. In finite element analysis, the stress concentration was lower in the restored tooth compared to the tooth without restoration, whereas in the restored teeth, the stress concentration was similar, regardless of the material used for the base or restoration. It can be concluded that the inlay materials combined with a base showed similar behavior and were not able to regain the strength of intact tooth structure.

Influence of light intensity on surface free energy and dentin bond strength of core build-up resins.

OBJECTIVE: We examined the influence of light intensity on surface free energy characteristics and dentin bond strength of dual-cure direct core build-up resin systems. METHODS: Two commercially available dual-cure direct core build-up resin systems, Clearfil DC Core Automix with Clearfil Bond SE One and UniFil Core EM with Self-Etching Bond, were studied. Bovine mandibular incisors were mounted in acrylic resin and the facial dentin surfaces were wet ground on 600-grit silicon carbide paper. Adhesives were applied to dentin surfaces and cured with light intensities of 0 (no irradiation), 200, 400, and 600 mW/cm(2). The surface free energy of the adhesives (five samples per group) was determined by measuring the contact angles of three test liquids placed on the cured adhesives. To determine the strength of the dentin bond, the core build-up resin pastes were condensed into the mold on the adhesive-treated dentin surfaces according to the methods described for the surface free energy measurement. The resin pastes were cured with the same light intensities as those used for the adhesives. Ten specimens per group were stored in water maintained at 37°C for 24 hours, after which they were shear tested at a crosshead speed of 1.0 mm/minute in a universal testing machine. Two-way analysis of variance (ANOVA) and a Tukey-Kramer test were performed, with the significance level set at 0.05. RESULTS: The surface free energies of the adhesive-treated dentin surfaces decreased with an increase in the light intensity of the curing unit. Two-way ANOVA revealed that the type of core build-up system and the light intensity significantly influence the bond strength, although there was no significant interaction between the two factors. The highest bond strengths were achieved when the resin pastes were cured with the strongest light intensity for all the core build-up systems. When polymerized with a light intensity of 200 mW/cm(2) or less, significantly lower bond strengths were observed. CONClUSIONS: The data suggest that the dentin bond strength of core build-up systems are still affected by the light intensity of the curing unit, which is based on the surface free energy of the adhesives. On the basis of the results and limitations of the test conditions used in this study, it appears that a light intensity of >400 mW/cm(2) may be required for achieving the optimal dentin bond strength.

Fracture resistance and microleakage of endocrowns utilizing three CAD-CAM blocks.

This study assessed marginal leakage and fracture resistance of computer-aided design/computer-aided manufacturing (CAD/CAM) fabricated ceramic crowns with intracoronal extensions into the pulp chambers of endodontically treated teeth (endocrowns) using either feldspathic porcelain (CEREC Blocks [CB], Sirona Dental Systems GmbH, Bensheim, Germany), lithium disilicate (e.max [EX], Ivoclar Vivadent, Schaan, Liechtenstein), or resin nanoceramic (Lava Ultimate [LU], 3M ESPE, St Paul, MN, USA).). Thirty extracted human permanent maxillary molars were endodontically treated. Standardized preparations were done with 2-mm intracoronal extensions of the endocrowns into the pulp chamber. Teeth were divided into three groups (n=10); each group was restored with standardized CAD/CAM fabricated endocrowns using one of the three tested materials. After cementation with resin cement, specimens were stored in distilled water at 37°C for one week, subjected to thermocycling, and immersed in a 5% methylene-blue dye solution for 24 hours. A compressive load was applied at 35 degrees to long axis of the teeth using a universal testing machine until failure. Failure load was recorded, and specimens were examined under a stereomicroscope for modes of failure and microleakage. Results were analyzed using one-way analysis of variance and Bonferroni post hoc multiple comparison tests (α=0.05). LU showed significantly (p<0.05) higher fracture resistance and more favorable fracture mode (ie, fracture of the endocrown without fracture of tooth) as well as higher dye penetration than CB and EX. In conclusion, although using resin nanoceramic blocks for fabrication of endocrowns may result in better fracture resistance and a more favorable fracture mode than other investigated ceramic blocks, more microleakage may be expected with this material.