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Receptor Expressed in Lymphoid Tissues (RELT) is a human tumor necrosis factor receptor superfamily member (TNFRSF) that is expressed most prominently in cells and tissues of the hematopoietic system. RELL1 and RELL2 are two homologs that physically interact with RELT and co-localize with RELT at the plasma membrane. This study sought to further elucidate the function of RELT by identifying novel protein interactions with RELT family members. The transcription factor MyoD family inhibitor domain-containing (MDFIC) was identified in a yeast two-hybrid genetic screen using RELL1 as bait. MDFIC co-localizes with RELT family members at the plasma membrane; this co-localization was most prominently observed with RELL1 and RELL2. In vitro co-immunoprecipitation (Co-IP) was utilized to demonstrate that MDFIC physically interacts with RELT, RELL1, and RELL2. Co-IP using deletion mutants of MDFIC and RELT identified regions important for physical association between MDFIC and RELT family members and a computational analysis revealed that RELT family members are highly disordered proteins. Immunohistochemistry of normal human lymph nodes revealed RELT staining that was most prominent in macrophages. Interestingly, the level of RELT staining significantly increased progressively in low and high-grade B-cell lymphomas versus normal lymph nodes. RELT co-staining with CD20 was observed in B-cell lymphomas, indicating that RELT is expressed in malignant B cells. Collectively, these results further our understanding of RELT-associated signaling pathways, the protein structure of RELT family members, and provide preliminary evidence indicating an association of RELT with B-cell lymphomas., Highlights • RELT family members physically interact with MDFIC. • RELT is expressed in human lymph nodes, with prominent expression in macrophages. • RELT is expressed in malignant B cells associated with B-cell lymphomas. • RELT is a highly disordered protein.

PURPOSE The relationship between contact lens wettability and comfort has been extensively evaluated; however, a direct correlation between the characteristics of the pre-lens tear film and the symptoms associated with contact lens discomfort has yet to be established. In addition, there is relatively limited knowledge relating to the entire tear film kinetics during the inter-blink period in contact lens wearers. The purpose of this analysis was to identify the characteristics of the pre-lens tear film kinetics that may be associated with the symptoms of contact lens discomfort. METHODS The study population comprised 202 soft (hydrogel and silicone hydrogel) contact lens wearers attending pre-screening visits at the OTG-i research clinic. All participants completed the Ocular Surface Disease Index (OSDI) questionnaire and the tear film was quantified via post hoc, masked analysis of high definition digital Tearscope videos recorded at the visit. The tear film kinetics of the least symptomatic wearers (OSDI lowest quintile scores, n = 45) were compared to the tear film kinetics of the most symptomatic wearers (OSDI highest quintile scores, n = 43). The hypothesis tested was that the tear film kinetics of asymptomatic wearers were better than tear film kinetics of symptomatic wearers. RESULTS The distribution of lens types worn was as follows: Daily Disposable 46.5%, 1-Month Replacement 39.6%, and 2-Week Replacement 13.6%. 48.2% of lenses were silicone hydrogel and 51.8% hydrogel. Symptomatic wearers had a shorter break-up time (4.7 s vs. 6.0 s; p = 0.003), lesser surface coverage by the tear film during the interblink period (95.1% vs. 98.5%; p < 0.001) and greater surface exposure at the time of the blink (9.4% vs. 3.9%; p = 0.001). CONCLUSIONS The current study demonstrated that the tear film kinetics of asymptomatic and symptomatic contact lens wearers were different, the findings supporting the hypothesis of poorer tear film kinetics for symptomatic than asymptomatic wearers in a general contact lens wearing population.

Purpose To determine whether anxiety or depression is associated with takotsubo stress cardiomyopathy (TSCM). Methods A retrospective case-control study was conducted among 73 TSCM cases and 111 acute coronary syndrome (ACS) controls matched for age, sex, and cardiac catheterization date. The study was conducted between May 1, 2009, and February 28, 2010. The Hospital Anxiety and Depression Scale was completed by all participants after hospital discharge. The Hospital Anxiety and Depression Scale was used to assess psychological distress with measurement of anxiety and depression scores. The presence of a stressful emotional or physical trigger before the TSCM presentation was determined. Univariate testing was performed to quantify the associations between anxiety and depression and TSCM trigger status. Multivariable logistic regression was used to quantify the independent associations between anxiety and depression and TSCM status after controlling for relevant covariates. Results The mean anxiety score was 6.7 ± 4.7 for TSCM cases versus 5.4 ± 3.4 for ACS controls (P = .06). The mean depression score was 4.3 ± 3.7 for TSCM cases versus 4.0 ± 3.1 for controls (P = .61). Anxiety was particularly associated with TSCM status with an emotional trigger (P = .05). After multivariable adjustment, anxiety (OR = 1.13; 95% CI, 1.01-1.26; P = .03) was associated with TSCM status but depression was not (OR = 0.94; 95% CI, 0.83-1.05; P = .29). Conclusions In comparison with a control group with ACS, patients who presented with TSCM have higher levels of anxiety but not depression.

Purpose: The purpose was to compare the effect of the repeated usage of two care systems (one hydrogen peroxide cleaning and disinfecting system and one polyaminopropyl biguanide (PHMB) containing multi-purpose system) with silicone hydrogel contact lenses worn for three months on a daily wear modality. A specific aspect of interest was of the effect of the care systems on contact lens wettability. Methods: Seventy-four symptomatic contact lens wearers, habitually wearing either ACUVUE® OASYS® (n = 37) or PureVision™ (n = 37), constituted the study population. The study was a two-arm prospective, investigator-masked, bilateral study of three-month duration to evaluate the effects of CLEAR CARE® compared with renu® fresh™. The subjects were randomized to one of the two lens care systems. Contact lens wettability and surface cleanliness were assessed with the Tearscope and reported in terms of pre-lens non-invasive break-up time (PL-NIBUT) and visible deposits. Baseline assessments at enrollment were with the subjects’ own contact lenses worn for at least 6 h when using their habitual PHMB-preserved care system and at the dispensing visit with new contact lenses. At the follow-up visits, the contact lenses were worn for at least 6 h, and were at least 11 days old for ACUVUE® OASYS® and 25 days old for PureVision™. Results: The results obtained showed that: (i) with CLEAR CARE®, a significant improvement in contact lens wettability was recorded compared with the habitual care system at the three-month follow-up visit (mean median PL-NIBUT 5.8 vs. 4.0 s, p

Objective While patients with primary progressive aphasia (PPA) typically present with predominant language impairment, behavioural symptoms, such as apathy, are often under-recognised. We aimed to systematically characterise apathy across the three recognised subtypes of PPA, plus atypical right-lateralised presentations of semantic dementia, and to evaluate the impact of apathy on carer burden and psychological wellbeing. Methods Baseline assessments from 114 PPA patients were included: 31 left semantic dementia (left SD) 16 right semantic dementia (right SD), 30 progressive nonfluent aphasia (PNFA) and 37 logopenic progressive aphasia (LPA). Clinician (Neuropsychiatric Inventory; NPI) and carer rated (Cambridge Behavioural Inventory; CBI, Frontal Systems Behaviour Scale; FrSBe) measures were used to quantify symptoms of apathy, and carer burden and psychological wellbeing were determined using the Zarit Burden Interview and Depression, Anxiety and Stress Scale. Results On the NPI, symptoms of apathy were present in 39% left SD, 56% right SD, 33% PNFA and 43% LPA patients. Multiple regression analysis revealed that 17.9% of the variance in carer burden was uniquely explained by scores on carer rated measures of apathy (CBI, FrSBe), even after accounting for diagnosis, disease duration, and cognitive and language impairment. Conclusions Apathy is much more common than current diagnostic criteria for PPA would suggest, though the severity of apathy is similar across patient groups. Increased awareness and routine assessments of apathy symptoms are needed, together with targeted pharmacological and behavioural interventions. Moreover, as apathy substantially contributes to carer burden in PPA, psychoeducation addressing behavioural symptoms may be beneficial.

The use of LEDs for the commercial cultivation of macroalgae is becoming commonplace, as is adding value to glass structures such as green houses and aquaculture ponds via the use of transparent photovoltaic cells. The effect on photosynthesis and primary production by down regulating light to the red (600–700 nm) and blue (400–525 nm) parts of the spectrum was assessed on a consortium of two filamentous chlorophyte macroalgae species (Rhizoclonium sp. and Ulothrix sp.). The aim of the study was to determine the optimal wavelength for growth and to assess potential nutrient removal rates in anaerobic digestion piggery effluent. Under red and blue light oxygen evolution was reduced compared to the white light controls (WL = 3.490 > RL = 2.700 > BL = 0.800 mg O2 g biomass−1 h−1). Spectrum-adapted chlorophyll fluorescence results indicated that the highest rETRmax (9.080 ± 0.380 μmol electrons m−2 s−1) occurred when blue light was used. This was 10% greater than rETRmax when red light was used. Both blue and red light grown macroalgae showed significantly higher rETRmax compared to white light. Long-term adaptation to blue light yielded the highest rETRmax (5.550 ± 0.230 μmol electrons m−2 s−1), with an effective quantum yield (Fq/Fm′) of 0.75 ± 0.003. Productivity of the macroalgal consortium was greatest under white light (WL = 0.210 > RL = 0.129, BL = 0.110 g L−1 d−1); however red light yielded a three-fold increase in productivity when standardized against the irradiance received at the Light Harvesting Complex (RL = 6.45 × 10−3 > BL = 4.036 × 10−3 > RL = 2.377 × 10−3 g L−1 d−1 μmol photons m−2 s−1 (±SE)). These results indicate that red light provides the optimal light wavelength for maximum growth of the macroalgal consortium used.

Purpose To measure the degree of meibomian gland (MG) dropout in the lower eyelid determined by analysis of images obtained from the LipiView II (LVII) and the Keratograph 5M (K5M). Methods The inferior eyelid of each participant was imaged in a random order using both devices. All images were subjectively assessed by a single-masked investigator to determine the extent of MG loss using the Arita 4-point meiboscore grading scale. The images were also semi-objectively analyzed with ImageJ to calculate the percentage of MG dropout, by tracing around the non-glandular area and the total exposed area of the lower lid. Results Twenty participants (mean age 37 years, range 23–60, 60% female) completed the study. A significant difference in meiboscore (mean ± SD) was obtained between the LVII and the K5M (1.43 ± 0.78 vs. 1.90 ± 0.81, Z = 3.25, p = 0.001). The meiboscore 95% limit of agreement (LOA) ranged from −1.88 to +0.93. A significant difference was found with mean ImageJ percentage dropout between the LVII and the K5M (31.5% vs 43.4%, t = −4.8, p = 0.00003). The percentage dropout 95% LOA ranged from −42.79% to +19.06%. Conclusions LVII images had significantly lower meiboscores and less percentage MG dropout. Varying amounts of dropout were observed between the devices due the amount of eyelid that was typically everted and because of differences in image quality. These results indicate that these devices should not be used interchangeably to evaluate MG dropout.

Thymic epithelial cells (TECs), the primary stromal population in the thymus, are critical to establish the microenvironments required for generating self-tolerant, pathogen-responsive T cells. However, due to the inaccessibility of the thoracic cavity and the fragility of TECs, manipulating the thymus to modulate adaptive immune responses remains challenging. We developed a novel surgical procedure that allowed access to thymus glands for intrathymic injection (ITI), without the need to cut the manubrium of the sternum bone. Horizontal cuts of the muscle layers between the first and second bones of the rib cage expose the thymus with minimal side effects. This novel ITI procedure enabled us to implant 16.5-day embryonic TECs into an adult syngeneic recipients’ thymus. Long-term survival and colonization of the implanted TECs was observed via live imaging, flow cytometry, and immunohistochemistry. We further investigated if introduction of allogeneic TECs in the thymus promote negative selection against allo-reactive T cells and induce donor-specific immune tolerance. We engrafted B6 islets under the kidney capsules of chemically induced diabetic Balb/C mice, preconditioned with T-cell depletion sera and intrathymic injection of B6 16.5-day embryonic TECs. Prolonged survival of the transplanted islets was observed compared to sham-operated controls. Mixed lymphocyte reaction experiments further showed dampened T cell proliferation responses against donor B6 antigens. Moreover, increased levels of Foxp3+ T-regulatory cells were detected in Balb/C recipients with ITI of B6 TECs, suggesting that implanted TECs could also promote the generation of alloantigen-specific T regulatory cells in addition to facilitating negative selection of donor antigen-reactive T cells. Our results suggest that intrathymic transplantation of TECs could be an effective way to induce donor-specific immune tolerance with limited general immune suppression. Disclosure I. Pradhan: None. S. Wong-Noonan: None. S. Bertera: None. R.J. Lakomy: None. H. Cohen: None. D. Wells: None. M. Trucco: None. Y. Fan: None.

Behavioural-variant frontotemporal dementia is characterized by a number of ostensibly disparate clinical features, which have largely been considered independently. This update proposes an integrated conceptual framework for these symptoms, by bringing together findings from animal studies, functional neuroimaging and behavioural neurology. The combined evidence indicates that many of the clinical symptoms--such as altered eating behaviour; overspending and susceptibility to scams; reduced empathy and socially inappropriate behaviour; apathy and stereotyped/ritualistic behaviour--can be conceptualized as a common underlying deficiency in goal-directed behaviour and the concomitant emergence of habits. This view is supported by similarities between the characteristic patterns of frontostriatal and insular atrophy in behavioural-variant frontotemporal dementia and the circuitry of homologous brain regions responsible for goal-directed and habitual behaviour in animals. Appreciating the impact of disturbance in goal-directed behaviour provides a new, integrated understanding of the common mechanisms underpinning prototypical clinical symptoms in behavioural-variant frontotemporal dementia. Furthermore, by drawing parallels between animal and clinical research, this translational approach has important implications for the development and evaluation of novel therapeutic treatments, from animal models through to behavioural interventions and clinical trials in humans.10.1093/brain/awy123_video1awy123media15796485557001.

Objective: This study aimed to study the mobile phone addiction behavior and awareness on electromagnetic radiation (EMR) among a sample of Malaysian population. Methods: This online study was conducted between December 2015 and 2016. The study instrument comprised eight segments, namely, informed consent form, demographic details, habituation, mobile phone fact and EMR details, mobile phone awareness education, psychomotor (anxious behavior) analysis, and health issues. Frequency of the data was calculated and summarized in the results. Results: Totally, 409 respondents participated in the study. The mean age of the study participants was 22.88 (standard error = 0.24) years. Most of the study participants developed dependency with smartphone usage and had awareness (level 6) on EMR. No significant changes were found on mobile phone addiction behavior between the participants having accommodation on home and hostel. Conclusion: The study participants were aware about mobile phone/radiation hazards and many of them were extremely dependent on smartphones. One-fourth of the study population were found having feeling of wrist and hand pain because of smartphone use which may lead to further physiological and physiological complication.

Objectives: To increase awareness of wire brush bristle ingestion, review the literature relating to wire brush bristle ingestion, and describe an algorithm for management of wire brush bristle foreign bodies as well as a technique for bedside removal. Methods: The authors present a case of an accidental wire bristle ingestion that was successfully treated with bedside removal and describe a successful bedside technique for removal. For the literature review, the PubMed journal database and Google Scholar were queried using the search terms wire bristle, wire brush, grill brush, and grill bristle. Results: Twenty-three wire brush ingestions with upper aerodigestive presentations were identified in the medical literature. Bedside visualization was attempted in 10 patients and successful in 5. The foreign body was able to be removed at the bedside in 3 of these patients. Two patients were managed conservatively. The authors developed an algorithm for management based on these literature findings. Conclusion: Wire brush bristle ingestion is increasingly common in the literature, and a definitive algorithm does not exist for management. The authors present an algorithm for management and describe a technique for successful removal at the bedside.

1) To investigate how much training manual wheelchair users perceive is required to learn to use a rear-mounted power assist safely and confidently. 2) To evaluate how the power assist affected wheelchair users' ability to negotiate a standardized obstacle course, wheelchair skills capacity and wheelchair mobility confidence.This study used a pre- versus post-test intervention design. Outcome measures included a standardized obstacle course, and modified versions of the Wheelchair Skills Test 4.2 (WST) and the Wheelchair Confidence Measure.The 11 participants felt safe and confident using the power assist within one to two training sessions. However, some potential safety concerns were noted. Participants performed two obstacle course tasks significantly more quickly with the power assist.Participants felt safe using the device with limited training and the device facilitated some mobility task performance. Further research is needed to understand the outcomes of long-term, community use. Implications for Rehabilitation Most experienced wheelchair users wanted only one or two training sessions with a new rear mounted power assist device; however, some safety concerns were noted. The device did not appear to affect user's confidence. The device enabled users to perform some mobility tasks more quickly and allowed some users to perform some mobility tasks they were unable to perform in their regular MWC.

Social relevance has an enhancing effect on learning and subsequent memory retrieval. The ability to learn from and remember social interactions may impact on susceptibility to financial exploitation, which is elevated in individuals with dementia. The current study aimed to investigate learning and memory of social interactions, the relationship between performance and financial vulnerability and the neural substrates underpinning performance in 14 Alzheimer's disease (AD) and 20 behavioural-variant frontotemporal dementia (bvFTD) patients and 20 age-matched healthy controls. On a “trust game” task, participants invested virtual money with counterparts who acted either in a trustworthy or untrustworthy manner over repeated interactions. A non-social “lottery” condition was also included. Participants’ learning of trust/distrust responses and subsequent memory for the counterparts and nature of the interactions was assessed. Carer-rated profiles of financial vulnerability were also collected. Relative to controls, both patient groups showed attenuated learning of trust/distrust responses, and lower overall memory for social interactions. Despite poor learning performance, both AD and bvFTD patients showed better memory of social compared to non-social interactions. Importantly, better memory for social interactions was associated with lower financial vulnerability in AD, but not bvFTD. Learning and memory of social interactions was associated with medial temporal and temporoparietal atrophy in AD, whereas a wider network of frontostriatal, insular, fusiform and medial temporal regions was implicated in bvFTD. Our findings suggest that although social relevance influences memory to an extent in both AD and bvFTD, this is associated with vulnerability to financial exploitation in AD only, and is underpinned by changes to different neural substrates. Theoretically, these findings provide novel insights into potential mechanisms that give rise to vulnerability in people with dementia, and open avenues for possible interventions.

Background Further validation of the risk indicators / predictors for peri-implant diseases is required to allow clinicians and patients to make informed decisions and optimize dental implant treatment outcomes. The aim of this study was to build prediction models, using Chi-square automatic interaction detection (CHAID) analysis, to determine which systemic-, patient-, implant-, site-, surgical- and prostheses-related risk indicators had more impact on the onset of peri-implant diseases. Methods A retrospective analysis of 200 patients who received implant-supported prostheses between 1998 and 2011 was conducted to evaluate the prevalences and risk indicators for peri-implant mucositis and peri-implantitis. The data were further analyzed using CHAID to produce two predictive models. Results The prevalence of peri-implant mucositis was 20.2% and 10.2% for patients and implants, respectively, while the prevalence of peri-implantitis was 10.1% at the patient level and 5.4% at the implant level. CHAID decision tree analysis identified three predictors (history of treated periodontitis, absence of regular supportive peri-implant maintenance, and use of bone graft) for peri-implant mucositis and three predictors (smoking, absence of regular supportive peri-implant maintenance, and placement of ≥2 implants) for peri-implantitis. Conclusions Within the limitations of this study, CHAID decision tree analysis identified the most plausible risk indicators and provided two predictive models for use in a particular university setting that would allow early detection and ensure appropriate care and maintenance of patients at high risk of peri-implant diseases.

Acute infection is known to induce strong anti-tumor immune responses, but clinical translation has been hindered by the lack of an effective strategy to safely and consistently provoke a therapeutic response. These limitations are overcome with a novel treatment approach involving repeated subcutaneous delivery of a Klebsiella-derived investigational immunotherapeutic, QBKPN. In preclinical models of lung cancer, QBKPN administration consistently showed anti-cancer efficacy, which was dependent on Klebsiella pre-exposure, but was independent of adaptive immunity. Rather, QBKPN induced anti-tumor innate immunity that required NK cells and NKG2D engagement. QBKPN increased NK cells and macrophages in the lungs, altered macrophage polarization, and augmented the production of cytotoxic molecules. An exploratory trial in patients with non-small cell lung cancer demonstrated QBKPN was well tolerated, safe, and induced peripheral immune changes suggestive of macrophage polarization and reduction of PD-1 and PD-L1 expression on leukocytes. These data demonstrate preclinical efficacy, and clinical safety and tolerability, for this cancer immunotherapy strategy that exploits innate anti-tumor immune mechanisms.

Collaboration is a core component of work activities amongst flight attendants as they work to promote onboard safety and a high level of customer service. Yet it can be difficult to maintain efficient communication, situation awareness, and information exchange given the technologies currently available on airplanes. We present a prototype called "Smart Crew"; a smart watch application that allows flight attendants to maintain an awareness of each other and communicate through messaging with haptic feedback. It is designed with an emphasis on real time information access and direct communication between flight attendants regardless of their location.

Many people use public transit on a recurring basis to travel for work, school, or other activities. Yet rides can be isolating despite encountering the same people on a regular basis. We designed City Explorer, a city exploration transit game, to provide transit riders with a channel to strengthen the sense of community. In City Explorer, players collect points as they ride public transit. They can complete route-specific challenges and collaborate with other riders to multiply points by riding the same route. Players can also create geo-tagged posts to describe and share community-related information. We share our design requirements, followed by details of game features, and our implementation of City Explorer.

Collaboration is a core component of work activities amongst flight attendants as they work to promote onboard safety and a high level of customer service. Yet it can be difficult to maintain efficient communication, situation awareness, and information exchange given the technologies currently available on airplanes. We present a prototype called "Smart Crew"; a smart watch application that allows flight attendants to maintain an awareness of each other and communicate through messaging with haptic feedback. It is designed with an emphasis on real time information access and direct communication between flight attendants regardless of their location.

Despite accruing evidence for relative preservation of episodic memory in the semantic variant of primary progressive aphasia (previously semantic dementia), the neural basis for this remains unclear, particularly in light of their well-established hippocampal involvement. We recently investigated the Papez network of memory structures across pathological subtypes of behavioural variant frontotemporal dementia and demonstrated severe degeneration of all relay nodes, with the anterior thalamus in particular emerging as crucial for intact episodic memory. The present study investigated the status of key components of Papez circuit (hippocampus, mammillary bodies, anterior thalamus, cingulate cortex) and anterior temporal cortex using volumetric and quantitative cell counting methods in pathologically-confirmed cases with semantic variant of primary progressive aphasia (n = 8; 61-83 years; three males), behavioural variant frontotemporal dementia with TDP pathology (n = 9; 53-82 years; six males) and healthy controls (n = 8, 50-86 years; four males). Behavioural variant frontotemporal dementia cases with TDP pathology were selected because of the association between the semantic variant of primary progressive aphasia and TDP pathology. Our findings revealed that the semantic variant of primary progressive aphasia and behavioural variant frontotemporal dementia show similar degrees of anterior thalamic atrophy. The mammillary bodies and hippocampal body and tail were preserved in the semantic variant of primary progressive aphasia but were significantly atrophic in behavioural variant frontotemporal dementia. Importantly, atrophy in the anterior thalamus and mild progressive atrophy in the body of the hippocampus emerged as the main memory circuit regions correlated with increasing dementia severity in the semantic variant of primary progressive aphasia. Quantitation of neuronal populations in the cingulate cortices confirmed the selective loss of anterior cingulate von Economo neurons in behavioural variant frontotemporal dementia. We also show that by end-stage these neurons selectively degenerate in the semantic variant of primary progressive aphasia with preservation of neurons in the posterior cingulate cortex. Overall, our findings demonstrate for the first time, severe atrophy, although not necessarily neuronal loss, across all relay nodes of Papez circuit with the exception of the mammillary bodies and hippocampal body and tail in the semantic variant of primary progressive aphasia. Despite the longer disease course in the semantic variant of primary progressive aphasia compared with behavioural variant frontotemporal dementia, we suggest here that the neural preservation of crucial memory relays (hippocampal→mammillary bodies and posterior cingulate→hippocampus) likely reflects the conservation of specific episodic memory components observed in most patients with semantic variant of primary progressive aphasia.

The recently discovered hexanucleotide repeat expansion, C9ORF72, has been shown to be among the most common cause of familial behavioural variant frontotemporal dementia (bvFTD) and to be present in a significant minority of apparently sporadic cases. While mounting evidence points to prominent episodic memory dysfunction in bvFTD cases, recent reports have also suggested an amnestic profile in C9ORF72 mutation carriers. No study to date, however, has formally characterised the extent to which episodic memory is impaired in C9ORF72 mutation versus sporadic cases, or the underlying neural substrates of such deficits. We conducted a comparison of C9ORF72 (n = 8) and sporadic (n = 15) bvFTD cases using a battery of verbal and visual episodic memory tasks, and contrasted their performance with that of Alzheimer's disease (AD, n = 15) and healthy older control (n = 15) participants. Behaviourally, the two bvFTD groups displayed comparable episodic memory profiles, irrespective of task administered, with prominent impairments evident relative to Controls. Whole-brain voxel-based morphometry analyses revealed distinct neural correlates of episodic memory dysfunction in each patient group. Widespread atrophy in medial prefrontal, medial and lateral temporal cortices correlated robustly with episodic memory dysfunction in sporadic bvFTD cases. In contrast, atrophy in a distributed set of regions in the frontal, temporal, and parietal lobes including the posterior cingulate cortex, was implicated in episodic memory dysfunction in C9ORF72 cases. Our results demonstrate that while episodic memory is disrupted to the same extent irrespective of genetic predisposition in bvFTD, distinct neural changes specific to each patient group are evident. The involvement of medial and lateral parietal regions in episodic memory dysfunction in C9ORF72 cases is of particular significance and represents an avenue of considerable interest for future studies., Highlights • We assessed episodic memory in bvFTD patients with and without C9ORF72 mutations. • Episodic memory deficits were present in C9ORF72 cases relative to Controls. • C9ORF72 and sporadic bvFTD cases showed equivalent episodic memory profiles. • Neural substrates of memory disruption differed contingent on mutation status. • Medial and lateral parietal involvement in C9ORF72 memory deficits is notable.

Background: Memory impairment in behavioral variant frontotemporal dementia (bvFTD) is traditionally considered to be mild and attributed to prefrontal cortex dysfunction. Recent studies, however, indicated that some patients can present with a memory impairment of the hippocampal type, showing storage and consolidation deficits in addition to the more executive/prefrontal related encoding and strategic difficulties. Objective: This study aimed to study the relationship between executive functions (EF) and memory processes in bvFTD via a data-driven approach. Method: Participants consisted of 71 bvFTD (among which 60.6% had a lumbar puncture showing non-Alzheimer biomarker profile) and 60 controls (among which 45% had amyloid imaging showing a normal profile). EF were assessed by the Frontal Assessment Battery, semantic/lexical verbal fluency tests, and forward/backward digit spans. Patients were split into amnestic (n = 33) and non-amnestic (n = 38) subgroups based on normative data (total recall score) from the Free and Cued Selective Reminding Test (FCSRT). Relationships between FCSRT subscores and EF measures were explored through hierarchical clustering analysis, partial correlation analysis with an EF component, and automated linear modeling. Results: Convergent findings across the statistical approaches show that, overall, memory performance was independent from EF in bvFTD whereas the relationship was stronger in controls. Indeed, in bvFTD, memory performance did not cluster with EF, was not correlated with the EF component, and was only partially (4% – 12.7%) predicted by EF. Discussion: These findings show that executive dysfunctions cannot solely explain the memory deficits occurring in bvFTD. Indeed, some patients present with a genuine amnesia affecting storage and consolidation abilities, which are independent from executive dysfunctions. On the clinical level, this study highlights the importance of revising the neuropsychological diagnosis criteria for bvFTD.

Episodic memory recall processes in Alzheimer’s disease (AD) and behavioural variant frontotemporal dementia (bvFTD) can be similarly impaired, whereas recognition performance is more variable. A potential reason for this variability could be false-positive errors made on recognition trials and whether these errors are due to amnesia per se or a general over-endorsement of recognition items regardless of memory. The current study addressed this issue by analysing recognition performance on the Rey Auditory Verbal Learning Test (RAVLT) in 39 bvFTD, 77 AD and 61 control participants from two centres (India, Australia), as well as disinhibition assessed using the Hayling test. Whereas both AD and bvFTD patients were comparably impaired on delayed recall, bvFTD patients showed intact recognition performance in terms of the number of correct hits. However, both patient groups endorsed significantly more false-positives than controls, and bvFTD and AD patients scored equally poorly on a sensitivity index (correct hits - false-positives). Furthermore, measures of disinhibition were significantly associated with false positives in both groups, with a stronger relationship with false-positives in bvFTD. Voxel-based morphometry analyses revealed similar neural correlates of false positive endorsement across bvFTD and AD, with both patient groups showing involvement of prefrontal and Papez circuitry regions, such as medial temporal and thalamic regions, and a DTI analysis detected an emerging but non-significant trend between false positives and decreased fornix integrity in bvFTD only. These findings suggest that false-positive errors on recognition tests relate to similar mechanisms in bvFTD and AD, reflecting deficits in episodic memory processes and disinhibition. These findings highlight that current memory tests are not sufficient to accurately distinguish between bvFTD and AD patients.

Adherence to social norms is compromised in a variety of neuropsychiatric conditions. Functional neuroimaging studies have investigated social norm compliance in healthy individuals, leading to the identification of a network of fronto-subcortical regions that underpins this ability. However, there is a lack of corroborative evidence from human lesion models investigating the structural anatomy of norm compliance across this fronto-subcortical network. To address this, we developed a neuroeconomic task to investigate social norm compliance in a neurodegenerative lesion model: behavioural variant frontotemporal dementia, a condition characterized by gross social dysfunction. The task assessed norm compliance across three behaviours that are well-studied in the neuroeconomics literature: fairness, prosocial and punishing behaviours. We administered our novel version of the Ultimatum Game in 22 patients with behavioural variant frontotemporal dementia and 22 age-matched controls, to assess how decision-making behaviour was modulated in response to (i) fairness of monetary offers; and (ii) social context of monetary offers designed to produce either prosocial or punishing behaviours. Voxel-based morphometry was used to characterize patterns of grey matter atrophy associated with task performance. Acceptance rates between patients and controls were equivalent when only fairness was manipulated. However, patients were impaired in modulating their decisions in response to social contextual information. Patients' performance in the punishment condition was consistent with a reduced tendency to engage in punishment; this was associated with decreased grey matter volume in the anterior cingulate, orbitofrontal cortex, left dorsolateral prefrontal cortex and right inferior frontal gyrus. In the prosocial condition, patients' performance suggested a reduced expression of prosocial behaviour, associated with decreased grey matter in the anterior insula, lateral orbitofrontal cortex, anterior cingulate and dorsal striatum. Acceptance rates in the Ultimatum Game were also significantly related to impairments in the everyday expression of empathic concern. In conclusion, we demonstrate that compliance to basic social norms (fairness) can be maintained in behavioural variant frontotemporal dementia; however, more complex normative behaviours (prosociality, punishment) that require integration of social contextual information are disrupted in association with atrophy in key fronto-striatal regions. These results suggest that the integration of social contextual information to guide normative behaviour is uniquely impaired in behavioural variant frontotemporal dementia, and may explain other common features of the condition including gullibility and impaired empathy. Our findings also converge with previous functional neuroimaging investigations in healthy individuals and provide the first description of the structural anatomy of social norm compliance in a neurodegenerative lesion model.

The principal objective of this investigation was to assess the symptomatic relief associated with eyelid hygiene using Blephaclean eye pads, a cosmetic product, to manage anterior blepharitis or Meibomian gland dysfunction (MGD) associated with dry eye complaints.The investigation was a bilateral, prospective, interventional open label investigation of 3-month duration. The test population was made up of dry eye sufferers with at least mild symptoms (Ocular Surface Disease Index [OSDI] ≥13) who presented with mild to moderate anterior blepharitis or MGD. Eyelid hygiene was intensive (twice a day) for the initial 3 weeks and a maintenance regimen (once a day) for the remainder of the study. At each visit, a detailed assessment of symptomatology was carried out. The assessment included the reporting of overall symptomatology with the OSDI questionnaire, of comfort and specific symptoms at the end of the day on 100-point visual analog scales and of specific MGD-related symptoms on forced choice 5-point scales.Forty subjects aged 22 to 74 years (54±15 years) were enrolled, of whom 39 completed the investigation. The product usage revealed good overall compliance throughout the study. The results revealed significant improvement in symptomatology. A significant (P0.001) decrease in overall symptomatology was recorded (Mean OSDI: baseline=30, day 21=18, day 90=19; Symptomatic status: baseline 100%, day 21 55%, day 90 54%) associated with significant (P0.001) increase in the end of day comfort (Mean score: baseline=56, day 21=67, day 90=67) and decrease in end of day dryness (Mean score: baseline=55, day 21=42, day 90=41).The results showed that eyelid hygiene with Blephaclean wipes by subjects with anterior blepharitis or MGD significantly decreased their associated symptomatology and increased their ocular comfort. The data confirmed the efficiency of the clinical methodology, put forward of 3 weeks of intensive use (twice a day) of eyelid wipes followed by maintenance use (once a day); that approach achieved a rapid symptomatic improvement that was maintained over time.

Separation and isolation of specific cell populations from solid immune organs are essential steps in immunological research. While antibody-labeling based cell sorting techniques, such as FACS, offer the possibility of isolating rare cells from a large background population, the cost and lengthy preparation time associated with these approaches remain burdensome for many researchers. Here, we report a rapid partitioning method that allows the separation of immune cells based on their size and density using a novel, spiral designed, microfluidic device (MFD) (Hou et al., 2016) Representing less than 0.5% of the total thymic cells, thymic epithelial cells (TECs) are critical for the generation of diverse T cell populations, essential for acquired immunity. Due to their rarity, separating TECs from the large pool of thymocytes is challenging. Using a MFD, we achieved substantial enrichment of TECs (up to 20X), high cell recovery (>2.5X of the traditional density gradient method) and excellent cell viability (>90%) within 7 minutes/thymus. High-purity TEC populations were obtained through further depletion of CD45+ thymic stromal cells using MACS. Thymus organoids reconstructed with TECs can support the development of both CD4+ and CD8+ T cells in vitro, proving the function of the isolated TECs. In addition, MFD could also be utilized to separate immune cell subtypes from spleen and lymph nodes. Notably, significant enrichment of CDllc+ MHCII+ dendritic cells (~15X) was achieved without RBC lysis and antibody labeling. In conclusion, our data suggest that the MFD partitioning method is efficient and cost-effective for rapid size-based separation of immune cells from primary and secondary immune organs for downstream applications.

The ground (X1A′) and two lowest lying excited singlet states (11A″ and 21A′) of methyl hypochlorite have been examined using ab initio electronic structure techniques to validate computationally efficient methods, upon which direct dynamics can be based, versus high-level ones, for which direct dynamics would be intractable. Ground-state equilibrium geometries and vibrational frequencies determined using density functional theory (DFT) with the 6-31G(d) basis set are tested against coupled-cluster theory (CCSD(T)) results from the literature. Vertical excitation energies and transition dipole moments calculated at the complete active space self-consistent field CASSCF/6-31+G(d) level of theory are benchmarked against multireference configuration interaction (MRCI) results with the aug-cc-pVXZ (X = D, T, Q) family of basis sets. The excited-state gradients that will govern the classical dynamics are compared for CASSCF/6-31+G(d) versus MRCI/aug-cc-pVXZ (X = D, T). To carry out the ab initio molecular dynamics (AIMD), existing electronic structure codes have been interfaced with the molecular modelling toolkit (MMTK), an open-source program library for molecular simulation applications. We use two examples to demonstrate the use of direct dynamics in MMTK: a canonical ground-state trajectory to sample positions and momenta, and an excited-state microcanonical trajectory based on CASSCF. The work presented here forms the basis for future study of the photodissociation of CH3OCl. As well, the implementation of AIMD within MMTK provides a useful tool for examining a variety of other research problems.

Multidrug-resistant Acinetobacter baumannii infection has presented a global medical challenge. The antibiograms of paired colistin-susceptible and -resistant strains revealed increased susceptibility of colistin-resistant strains to most tested antibiotics, including those that are active against only gram-positive bacteria. Synergy between colistin and rifampicin was observed in the colistin-susceptible strains. The ability to form biofilm in the colistin-resistant strains was significantly lower (P

Null hypothesis significance testing (NHST) dominates quantitative data analysis, but its use is controversial and has been heavily criticized. The American Psychological Association has advocated the reporting of effect sizes (ES), confidence intervals (CIs), and statistical power analysis to complement NHST results to provide a more comprehensive understanding of research findings. The aim of this paper is to carry out a sample survey of statistical reporting practices in two journals with the highest h5-index scores in the areas of developmental disability and rehabilitation. Using a checklist that includes critical recommendations by American Psychological Association, we examined 100 randomly selected articles out of 456 articles reporting inferential statistics in the year 2013 in the Journal of Autism and Developmental Disorders (JADD) and Research in Developmental Disabilities (RDD). The results showed that for both journals, ES were reported only half the time (JADD 59.3%; RDD 55.87%). These findings are similar to psychology journals, but are in stark contrast to ES reporting in educational journals (73%). Furthermore, a priori power and sample size determination (JADD 10%; RDD 6%), along with reporting and interpreting precision measures (CI: JADD 13.33%; RDD 16.67%), were the least reported metrics in these journals, but not dissimilar to journals in other disciplines. To advance the science in developmental disability and rehabilitation and to bridge the research-to-practice divide, reforms in statistical reporting, such as providing supplemental measures to NHST, are clearly needed.

Objective : Preclinical medical student electives are prevalent at medical schools across the United States, but the range of electives available and their impact on medical student education are not well described in the literature. The objective of this article is to review the literature relating to preclinical medical student electives and their impact on medical student educational outcomes. Methods : We reviewed studies that met the following criteria: English-language articles describing preclinical US-based medical electives. We used PubMed journal databases and limited our search for the time period 1999–2014. We excluded electives based in other countries or electives designed for third or fourth year students. Data abstracted included the topic of the elective, qualitative descriptions of the electives, and any associated surveys or exam data associated with the electives. Data were synthesized using descriptive tables sorting electives by broad topic. Reported outcomes and statistical methods were analyzed to assess study quality. Results : We found a wide range of subjects taught in the form of preclinical medical school electives. We identified electives in clinical skills, the humanities, student lifestyle, specialty-specific electives, and an assortment of other miscellaneous electives. Surveys and exams administered to students showed that the electives were universally well received by students. Of the 37 electives identified, 15 electives used quantitative objective assessments, such as knowledge exams, while the remaining tended to use student self-reported results. Conclusions : Preclinical medical student electives are prevalent at medical schools across the United States and have a significant impact on medical student education. Keywords: humanities; education; medical student; electives; undergraduate; preclinical; curriculum (Published: 11 May 2015) Citation: Med Educ Online 2015, 20: 26615 - http://dx.doi.org/10.3402/meo.v20.26615 To access the supplementary material for this article, please see Supplementary files under ‘Article Tools’

Purpose Random item generation (RIG) involves central executive functioning. Measuring aspects of random sequences can therefore provide a simple method to complement other tools for cognitive assessment. We examine the extent to which RIG relates to specific measures of cognitive function, and whether those measures can be estimated using RIG only. Method Twelve healthy older adults (age: M = 70.3 years, SD = 4.9; 8 women and 4 men) and 20 healthy young adults (age: M = 24 years, SD = 4.0; 12 women and 8 men) participated in this pilot study. Each completed a RIG task, along with the color Stroop test, the Repeatable Battery for the Assessment of Neuropsychological Status, and the Peabody Picture Vocabulary Test–Fourth Edition (Dunn & Dunn, 2007). Several statistical features extracted from RIG sequences, including recurrence quantification, were found to be related to the other measures through correlation, regression, and a neural-network model. Results The authors found significant effects of age in RIG and demonstrate that nonlinear machine learning can use measures of RIG to accurately predict outcomes from other tools. Conclusions These results suggest that RIG can be used as a relatively simple predictor for other tools and in particular seems promising as a potential screening tool for selective attention in healthy aging. Supplemental Material https://doi.org/10.23641/asha.14963904

Visual and auditory systems interact at both cortical and subcortical levels. Studies suggest a highly context-specific cross-modal modulation of the auditory system by the visual system. The present study builds on this work by sampling data from 17 young healthy adults to test whether visual speech stimuli evoke different responses in the auditory efferent system compared to visual non-speech stimuli. The descending cortical influences on medial olivocochlear (MOC) activity were indirectly assessed by examining the effects of contralateral suppression of transient-evoked otoacoustic emissions (TEOAEs) at 1, 2, 3 and 4 kHz under three conditions: (a) in the absence of any contralateral noise (Baseline), (b) contralateral noise + observing facial speech gestures related to productions of vowels /a/ and /u/ and (c) contralateral noise + observing facial non-speech gestures related to smiling and frowning. The results are based on 7 individuals whose data met strict recording criteria and indicated a significant difference in TEOAE suppression between observing speech gestures relative to the non-speech gestures, but only at the 1 kHz frequency. These results suggest that observing a speech gesture compared to a non-speech gesture may trigger a difference in MOC activity, possibly to enhance peripheral neural encoding. If such findings can be reproduced in future research, sensory perception models and theories positing the downstream convergence of unisensory streams of information in the cortex may need to be revised.

CC49 is a clinically validated antibody with specificity for TAG-72, a carbohydrate epitope that is over-expressed and exposed on a large fraction of solid malignancies. We constructed a single chain fragment (scFv) based on CC49 and fused it to beta-lactamase. The first generation fusion protein, TAB2.4, was expressed at low levels in Escherichia coli and significant degradation was observed during production. We optimized the scFv domain of TAB2.4 by Combinatorial Consensus Mutagenesis (CCM). An improved variant TAB2.5 was identified that resulted in an almost 4-fold improved expression and 2.5 degrees higher thermostability relative to its parent molecule. Soluble TAB2.5 can be manufactured in low-density E.coli cultures at 120 mg/l. Our studies suggest that CCM is a rapid and efficient method to generate antibody fragments with improved stability and expression. The fusion protein TAB2.5 can be used for antibody directed enzyme prodrug therapy (ADEPT).

Spatial disorientation is a prominent feature of early Alzheimer's disease (AD) attributed to degeneration of medial temporal and parietal brain regions, including the retrosplenial cortex (RSC). By contrast, frontotemporal dementia (FTD) syndromes show generally intact spatial orientation at presentation. However, currently no clinical tasks are routinely administered to objectively assess spatial orientation in these neurodegenerative conditions. In this study we investigated spatial orientation in 58 dementia patients and 23 healthy controls using a novel virtual supermarket task as well as voxel-based morphometry (VBM). We compared performance on this task with visual and verbal memory function, which has traditionally been used to discriminate between AD and FTD. Participants viewed a series of videos from a first person perspective travelling through a virtual supermarket and were required to maintain orientation to a starting location. Analyses revealed significantly impaired spatial orientation in AD, compared to FTD patient groups. Spatial orientation performance was found to discriminate AD and FTD patient groups to a very high degree at presentation. More importantly, integrity of the RSC was identified as a key neural correlate of orientation performance. These findings confirm the notion that i) it is feasible to assess spatial orientation objectively via our novel Supermarket task; ii) impaired orientation is a prominent feature that can be applied clinically to discriminate between AD and FTD and iii) the RSC emerges as a critical biomarker to assess spatial orientation deficits in these neurodegenerative conditions.