Loss of Cadherin-11 in pancreatic ductal adenocarcinoma alters tumor-immune microenvironment.

Pancreatic ductal adenocarcinoma (PDAC) is one of the top five deadliest forms of cancer with very few treatment options. The 5-year survival rate for PDAC is 10% following diagnosis. Cadherin 11 (Cdh11), a cell-to-cell adhesion molecule, has been suggested to promote tumor growth and immunosuppression in PDAC, and Cdh11 inhibition significantly extended survival in mice with PDAC. However, the mechanisms by which Cdh11 deficiency influences PDAC progression and anti-tumor immune responses have yet to be fully elucidated. To investigate Cdh11-deficiency induced changes in PDAC tumor microenvironment (TME), we crossed p48-Cre; LSL-KrasG12D/+; LSL-Trp53R172H/+ (KPC) mice with Cdh11+/- mice and performed single-cell RNA sequencing (scRNA-seq) of the non-immune (CD45-) and immune (CD45+) compartment of KPC tumor-bearing Cdh11 proficient (KPC-Cdh11+/+) and Cdh11 deficient (KPC-Cdh11+/-) mice. Our analysis showed that Cdh11 is expressed primarily in cancer-associated fibroblasts (CAFs) and at low levels in epithelial cells undergoing epithelial-to-mesenchymal transition (EMT). Cdh11 deficiency altered the molecular profile of CAFs, leading to a decrease in the expression of myofibroblast markers such as Acta2 and Tagln and cytokines such as Il6, Il33 and Midkine (Mdk). We also observed a significant decrease in the presence of monocytes/macrophages and neutrophils in KPC-Cdh11+/- tumors while the proportion of T cells was increased. Additionally, myeloid lineage cells from Cdh11-deficient tumors had reduced expression of immunosuppressive cytokines that have previously been shown to play a role in immune suppression. In summary, our data suggests that Cdh11 deficiency significantly alters the fibroblast and immune microenvironments and contributes to the reduction of immunosuppressive cytokines, leading to an increase in anti-tumor immunity and enhanced survival.

Facial Anthropometric Norms of the Young Black South African Woman.

Ethnic pride and the push toward preservation of ethnicity in all areas of aesthetic and reconstructive medicine has created the need for normative facial anthropometric data specific to localized geographical populations. This study aimed to gather a set of soft tissue anthropometric norms for the young Black South African woman and to compare this with international data and neoclassical anthropometric maxims. Methods: In total, 156 Black female students from Sefako Makgatho University between 18 and 25 years of age, with a normal dental occlusion and a normal body mass index were included in the study. Computer-based photographic analysis of participants' faces in anterior, lateral, and basal views was undertaken under strict studio conditions and compared with international studies. Results: Facial height proportions tended toward a smaller upper facial third in comparison with mid and lower facial thirds. Nasal width was greater than other populations, and exceeded the neoclassical canon of one-fifth of facial width. Nasal tip projection was greater than Congolese and African American counterparts. Vermilion height ratios approximated a ratio of 1:1 with lip protrusion beyond the classical Rickets E-line. Conclusions: The "classical" anthropometric measurements most often quoted in academic literature, although important in their own right, do not consider the distinct differences in facial anthropometric norms between population and racial groups. These differences must be taken into consideration to preserve ethnic traits and optimize aesthetic outcomes.

Apraxia of speech with phonological alexia and agraphia following resection of the left middle precentral gyrus: illustrative case.

BACKGROUND: Apraxia of speech is a disorder of speech-motor planning in which articulation is effortful and error-prone despite normal strength of the articulators. Phonological alexia and agraphia are disorders of reading and writing disproportionately affecting unfamiliar words. These disorders are almost always accompanied by aphasia. OBSERVATIONS: A 36-year-old woman underwent resection of a grade IV astrocytoma based in the left middle precentral gyrus, including a cortical site associated with speech arrest during electrocortical stimulation mapping. Following surgery, she exhibited moderate apraxia of speech and difficulty with reading and spelling, both of which improved but persisted 6 months after surgery. A battery of speech and language assessments was administered, revealing preserved comprehension, naming, cognition, and orofacial praxis, with largely isolated deficits in speech-motor planning and the spelling and reading of nonwords. LESSONS: This case describes a specific constellation of speech-motor and written language symptoms-apraxia of speech, phonological agraphia, and phonological alexia in the absence of aphasia-which the authors theorize may be attributable to disruption of a single process of "motor-phonological sequencing." The middle precentral gyrus may play an important role in the planning of motorically complex phonological sequences for production, independent of output modality.

Testing the efficacy of real-time fMRI neurofeedback for training people who smoke daily to upregulate neural responses to nondrug rewards.

Although the use of nondrug rewards (e.g., money) to facilitate smoking cessation is widespread, recent research has found that such rewards may be least effective when people who smoke cigarettes are tempted to do so. Specifically, among people who smoke, the neural response to nondrug rewards appears blunted when access to cigarettes is anticipated, and this blunting is linked to a decrease in willingness to refrain from smoking to earn a monetary incentive. Accordingly, methods to enhance the value of nondrug rewards may be theoretically and clinically important. The current proof-of-concept study tested if real-time fMRI neurofeedback training augments the ability to upregulate responses in reward-related brain areas relative to a no-feedback control condition in people who smoke. Adults (n = 44, age range = 20-44) who reported smoking >5 cigarettes per day completed the study. Those in the intervention group (n = 22, 5 females) were trained to upregulate brain responses using feedback of ongoing striatal activity (i.e., a dynamic "thermometer" that reflected ongoing changes of fMRI signal intensity in the striatum) in a single neurofeedback session with three training runs. The control group (n = 22, 5 females) underwent a nearly identical procedure but received no neurofeedback. Those who received neurofeedback training demonstrated significantly greater increases in striatal BOLD activation while attempting to think about something rewarding compared to controls, but this effect was present only during the first training run. Future neurofeedback research with those who smoke should explore how to make neurofeedback training more effective for the self-regulation of reward-related brain activities.

Modulation of Radiation Biomarkers in a Randomized Phase II Study of 131I-MIBG With or Without Radiation Sensitizers for Relapsed or Refractory Neuroblastoma.

PURPOSE: 131I-metaiodobenzylguanidine (131I-MIBG) has demonstrated efficacy as a single agent in neuroblastoma. Recent trials have focused on 131I-MIBG combination strategies, though little is known about the effect of putative radiosensitizers on biological markers of radiation exposure. METHODS AND MATERIALS: NANT2011-01 evaluated 131I-MIBG therapy alone (arm A) or in combination with vincristine/irinotecan (arm B) or vorinostat (arm C) for patients with relapsed or refractory neuroblastoma. Blood samples were collected before and after 131I-MIBG infusion to determine levels of radiation-associated biomarkers (transcript and protein). The association of biomarker with treatment arm, clinical response, and treatment toxicity was analyzed. RESULTS: The cohort included 99 patients who had at least 1 biomarker available for analysis. Significant modulation in most biomarkers between baseline, 72, and 96 hours following 131I-MIBG was observed. Patients in arm C had the lowest degree of modulation in FLT3 ligand protein. Lower baseline BCL2 transcript levels were associated with higher overall response. Patients with greater increases in FLT3 ligand at 96 hours after 131I-MIBG therapy were significantly more likely to have grade 4 thrombocytopenia. Peripheral blood gene expression of the BCL2 family of apoptotic markers (BCL2L1 and BAX transcripts) was significantly associated with grade 4 hematologic toxicity. RNA sequencing demonstrated little overlap in the top modulated peripheral blood transcripts between randomized arms. CONCLUSIONS: Peripheral blood biomarkers relevant to radiation exposure demonstrate significant modulation after 131I-MIBG and concomitant radiation sensitizers affect extent of modulation. Biomarkers related to hematopoietic damage and apoptosis were associated with hematologic toxicity.

Momentary associations between affect and craving as a function of perceived smoking opportunity in young adults smoking 1-5 cigarettes per day: An ecological momentary assessment study.

BACKGROUND: Very light daily smoking (1-5 cigarettes/day) is associated with adverse consequences and is prevalent among young adults. Evidence suggests that perceived smoking opportunity modulates links between affect and craving in adults with heavier smoking patterns (e.g., > 10 cigarettes per day), but there is a lack of similar data in young adults with very light daily smoking patterns. This study addresses this gap by investigating the associations between affect and craving as a function of perceived smoking opportunity under naturalistic conditions. METHODS: Forty-one young adults aged 18-25 (M=21.03, SD=1.75) who reported smoking 1-5 cigarettes per day (M=3.2, SD=1.2) completed intermittent ratings of momentary affective valence and arousal, smoking craving, and perceived smoking opportunity on smartphones five times per day for seven days. RESULTS: Multilevel analyses suggested that when participants felt more pleasant or unpleasant, they were likely to report more intense craving. When smoking opportunity was perceived as high, affective arousal was positively associated with craving; this association was not observed when opportunity to smoke was perceived as low. CONCLUSIONS: These findings indicate that higher momentary intensity of affective valence (both negative and positive) is linked to stronger momentary craving in young adults who report very light daily smoking. Anticipating an opportunity to satisfy craving by smoking may strengthen the association between reported affective arousal and craving in this population. These results highlight the potential benefits of coping with craving (e.g., by regulating affect) for those who engage in light tobacco use, especially in environments with high cigarette availability.

Dissociation of Broca's area from Broca's aphasia in patients undergoing neurosurgical resections.

OBJECTIVE: Broca's aphasia is a syndrome of impaired fluency with retained comprehension. The authors used an unbiased algorithm to examine which neuroanatomical areas are most likely to result in Broca's aphasia following surgical lesions. METHODS: Patients were prospectively evaluated with standardized language batteries before and after surgery. Broca's area was defined anatomically as the pars opercularis and triangularis of the inferior frontal gyrus. Broca's aphasia was defined by the Western Aphasia Battery language assessment. Resections were outlined from MRI scans to construct 3D volumes of interest. These were aligned using a nonlinear transformation to Montreal Neurological Institute brain space. A voxel-based lesion-symptom mapping (VLSM) algorithm was used to test for areas statistically associated with Broca's aphasia when incorporated into a resection, as well as areas associated with deficits in fluency independent of Western Aphasia Battery classification. Postoperative MRI scans were reviewed in blinded fashion to estimate the percentage resection of Broca's area compared to areas identified using the VLSM algorithm. RESULTS: A total of 289 patients had early language evaluations, of whom 19 had postoperative Broca's aphasia. VLSM analysis revealed an area that was highly correlated (p < 0.001) with Broca's aphasia, spanning ventral sensorimotor cortex and supramarginal gyri, as well as extending into subcortical white matter tracts. Reduced fluency scores were significantly associated with an overlapping region of interest. The fluency score was negatively correlated with fraction of resected precentral, postcentral, and supramarginal components of the VLSM area. CONCLUSIONS: Broca's aphasia does not typically arise from neurosurgical resections in Broca's area. When Broca's aphasia does occur after surgery, it is typically in the early postoperative period, improves by 1 month, and is associated with resections of ventral sensorimotor cortex and supramarginal gyri.

Evaluating syntactic comprehension during awake intraoperative cortical stimulation mapping.

OBJECTIVE: Electrocortical stimulation mapping (ECS) is widely used to identify essential language areas, but sentence-level processing has rarely been investigated. METHODS: While undergoing awake surgery in the dominant left hemisphere, 6 subjects were asked to comprehend sentences varying in their demands on syntactic processing. RESULTS: In all 6 subjects, stimulation of the inferior frontal gyrus disrupted comprehension of passive sentences, which critically depend on syntactic processing to correctly assign grammatical roles, without disrupting comprehension of simpler tasks. In 4 of the 6 subjects, these sites were localized to the pars opercularis. Sentence comprehension was also disrupted by stimulation of other perisylvian sites, but in a more variable manner. CONCLUSIONS: These findings suggest that there may be language regions that differentially contribute to sentence processing and which therefore are best identified using sentence-level tasks. The functional consequences of resecting these sites remain to be investigated.

Pilot randomized controlled trial evaluating the effect of random nicotine delivery on cigarettes per day and smoke exposure.

BACKGROUND: Many smokers report attempting to quit each year, yet most relapse, in part due to exposure to smoking-related cues. It is hypothesized that extinction of the cue-drug association could be facilitated through random nicotine delivery (RND), thus making it easier for smokers to quit. The current study aimed to evaluate the effects of RND on smoking cessation-related outcomes including cigarettes per day (CPD) and exhaled carbon monoxide (CO). METHODS: Participants were current smokers (>9 CPD) interested in quitting. Novel trans-mucosal, orally dissolving nicotine films, developed by Bionex Pharmaceuticals, were used in the study. The pharmacokinetic profile of these films was assessed in single (Experiment 1) and multiple-dose (Experiment 2) administrations prior to the smoking cessation study (Experiment 3). In Experiment 3, participants were randomized 1:1:1 to recieve 4 nicotine films per day of either: placebo delivery (0 mg), steady-state delivery (2 mg), or random nicotine delivery (RND) (0 mg or 4 mg). After two weeks, participants were advised to quit (target quit date, TQD) and were followed up 4 weeks later to collect CPD and CO and to measure dependence (Penn State Cigarette Dependence Index; PSCDI) and craving (Questionnaire of Smoking Urges; QSU-Brief). Means and frequencies were used to describe the data and repeated measures ANOVA was used to determine differences between groups. RESULTS: The pharmacokinetic studies (Experiment 1 and 2) demonstrated that the films designed for this study delivered nicotine as expected, with the 4 mg film delivering a nicotine boost of approximately 12.4 ng/mL across both the single and the multiple dose administration studies. The films reduced craving for a cigarette and were well-tolerated, overall, and caused no changes in blood pressure or heart rate. Using these films in the cessation study (Experiment 3) (n = 45), there was a significant overall reduction in cigarettes smoked per day (CPD) and in exhaled CO, with no significant differences across groups (placebo, steady-state, RND). In addition, there were no group differences in dependence or craving. Adverse events included heartburn, hiccups, nausea, and to a lesser extent, vomiting and anxiety and there were no differences across groups. CONCLUSION: Overall, this pilot study found that RND via orally dissolving films was feasible and well tolerated by participants. However, RND participants did not experience a greater reduction in self-reported CPD and exhaled CO, compared with participants in the steady-state and placebo delivery groups. Future studies to evaluate optimal RND parameters with larger sample sizes are needed to fully understand the effect of RND on smoking cessation-related outcomes.

Trends in osteoporosis diagnosis and management in Australia.

Trends in bone mineral density monitoring, and drug treatment for osteoporosis, in Australia were examined. Rates of DEXA scanning have increased in response to changes to government policy affecting reimbursement. The drug denosumab is being utilised at an increasing rate, while bisphosphonate use has declined. Osteoporosis prevalence remained stable over the same timeframe, while rate of hip fractures declined, suggesting that introduction of osteoporosis screening was associated with a reduction in adverse osteoporosis outcomes, but may also have been associated with overutilisation. INTRODUCTION: Radiology interventions to diagnose and medications to manage osteoporosis in Australia are reimbursed under the Medicare benefits schedule (MBS) and Pharmaceutical Benefits Scheme (PBS). Monitoring of these databases enables changes in utilisation of these practices to be monitored over time. METHODS: This study examined rates of utilisation for bone mineral density (BMD) measurement and osteoporosis pharmacotherapy subsidised under the MBS. Rates of osteoporosis and hip fracture were estimated using data reported by the Australian Bureau of Statistics (ABS) and Australian Institute for Health and Welfare (AIHW). RESULTS: Rates of BMD measurement increased since the technology was first reimbursed, with changes to policy regarding reimbursement for screening for individuals over 70 leading to an increase in BMD measurement after 2007. Prescribing rates also increased over time, initially with the introduction of oral bisphosphonates and subsequently for denosumab, which has subsequently become the most commonly prescribed agent for osteoporosis management in Australia, while bisphosphonate use has declined. Osteoporosis prevalence in Australia has remained relatively static at 3-4% of the population since 2001 to 2017, while rates of minimal trauma hip fracture hospitalisations have declined from 195 per 100,000 to 174 per 100,000 in the same timeframe. CONCLUSION: Available data indicates that osteoporosis screening rates changed over time from 2001 to 2018 and that changes to government policy had a significant effect on the rates at which screening was performed. Over the same timeframe, there was a sustained reduction in hip fracture hospitalisation rates, with no change to reported osteoporosis prevalence. This suggests that policy changes permitting unlimited access to BMD measurement were associated with a reduction in osteoporotic fractures, but may also have been associated with overutilisation. Prospective studies to assess the efficacy of specific policies to ensure screening is performed in accordance with best-practice guidelines may be desirable.

A novel high-throughput screening strategy for targeting alpha-synuclein and other long-lived proteins.

Small-molecule high-throughput screening (HTS) campaigns have frequently been used to identify lead molecules that can alter expression of disease-relevant proteins in cell-based assays. However, most cell-based HTS assays require short compound exposure periods to avoid toxicity and ensure that compounds are stable in media for the duration of the exposure. This limits the ability of HTS assays to detect inhibitors of the synthesis of target proteins with long half-lives, which can often exceed the exposure times utilized in most HTS campaigns. One such target is alpha-synuclein (α-syn)-a protein well-known for its pathological aggregation in Parkinson's Disease (PD) and other forms of neurodegeneration known collectively as synucleinopathies. Here, we report the development of an HTS assay using a CRISPR-engineered neuroblastoma cell line expressing a destabilized luciferase reporter inserted at the end of the coding region of the SNCA locus. The resultant destabilized fusion protein exhibited a significant reduction in half-life compared to the endogenous, unmodified α-syn protein, and accurately reported reductions in α-syn levels due to known protein translation inhibitors and specific α-syn siRNAs. The robustness and utility of this approach was shown by using the resulting cell line (dsLuc-Syn) to screen a focused library of 3,192 compounds for reduction of α-syn. These data demonstrate the general utility of converting endogenous loci into destabilized reporter genes capable of identifying inhibitors of gene expression of highly stable proteins even in short-term assays.

Comparison of technical errors in pediatric bitewing radiographs acquired with round vs rectangular collimation.

OBJECTIVE: To compare technical errors in bitewing radiographs acquired with round vs rectangular collimation in a hospital-based pediatric dentistry training program. STUDY DESIGN: A retrospective chart review was conducted of 176 digital bitewing radiographs exposed with round collimation and 106 exposed with rectangular collimation. The number of re-exposures was calculated, and errors in central ray entry (CRE; "cone cuts"), horizontal and vertical positioning, and angulation were measured. RESULTS: There were no greater re-exposures but significantly more CRE errors with rectangular collimation (21.7%; n = 23; 95% confidence interval [CI], 13.9%-30.0%) than with round collimation (3.4%; n = 6; 95% CI, 0.7%-6.1%). CRE error location, horizontal positioning errors, and size of horizontal overlapped contacts were statistically different but not clinically important. CONCLUSIONS: Use of rectangular collimation resulted in increased CRE errors but no other clinically significant problems. This technique should be used to reduce radiation exposure to patients.

The cyclic dinucleotide 2'3'-cGAMP induces a broad antibacterial and antiviral response in the sea anemone Nematostella vectensis.

In mammals, cyclic dinucleotides (CDNs) bind and activate STING to initiate an antiviral type I interferon response. CDNs and STING originated in bacteria and are present in most animals. By contrast, interferons are believed to have emerged in vertebrates; thus, the function of CDN signaling in invertebrates is unclear. Here, we use a CDN, 2'3' cyclic guanosine monophosphate-adenosine monophosphate (2'3'-cGAMP), to activate immune responses in a model cnidarian invertebrate, the starlet sea anemone Nematostella vectensis Using RNA sequencing, we found that 2'3'-cGAMP induces robust transcription of both antiviral and antibacterial genes in N. vectensis Many of the antiviral genes induced by 2'3'-cGAMP are homologs of vertebrate interferon-stimulated genes, implying that the interferon response predates the evolution of interferons. Knockdown experiments identified a role for NF-κB in specifically inducing antibacterial genes downstream of 2'3'-cGAMP. Some of these putative antibacterial genes were also found to be induced during Pseudomonas aeruginosa infection. We characterized the protein product of one of the putative antibacterial genes, the N. vectensis homolog of Dae4, and found that it has conserved antibacterial activity. This work suggests that a broad antibacterial and antiviral transcriptional response is an evolutionarily ancestral output of 2'3'-cGAMP signaling in animals.

Validation of a Crisis Standards of Care Model for Prioritization of Limited Resources During the Coronavirus Disease 2019 Crisis in an Urban, Safety-Net, Academic Medical Center.

OBJECTIVES: The coronavirus disease 2019 pandemic has overwhelmed healthcare resources even in wealthy nations, necessitating rationing of limited resources without previously established crisis standards of care protocols. In Massachusetts, triage guidelines were designed based on acute illness and chronic life-limiting conditions. In this study, we sought to retrospectively validate this protocol to cohorts of critically ill patients from our hospital. DESIGN: We applied our hospital-adopted guidelines, which defined severe and major chronic conditions as those associated with a greater than 50% likelihood of 1- and 5-year mortality, respectively, to a critically ill patient population. We investigated mortality for the same intervals. SETTING: An urban safety-net hospital ICU. PATIENTS: All adults hospitalized during April of 2015 and April 2019 identified through a clinical database search. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Of 365 admitted patients, 15.89% had one or more defined chronic life-limiting conditions. These patients had higher 1-year (46.55% vs 13.68%; p < 0.01) and 5-year (50.00% vs 17.22%; p < 0.01) mortality rates than those without underlying conditions. Irrespective of classification of disease severity, patients with metastatic cancer, congestive heart failure, end-stage renal disease, and neurodegenerative disease had greater than 50% 1-year mortality, whereas patients with chronic lung disease and cirrhosis had less than 50% 1-year mortality. Observed 1- and 5-year mortality for cirrhosis, heart failure, and metastatic cancer were more variable when subdivided into severe and major categories. CONCLUSIONS: Patients with major and severe chronic medical conditions overall had 46.55% and 50.00% mortality at 1 and 5 years, respectively. However, mortality varied between conditions. Our findings appear to support a crisis standards protocol which focuses on acute illness severity and only considers underlying conditions carrying a greater than 50% predicted likelihood of 1-year mortality. Modifications to the chronic lung disease, congestive heart failure, and cirrhosis criteria should be refined if they are to be included in future models.

Flavor and product messaging are the two most important drivers of electronic cigarette selection in a choice-based task.

Electronic cigarette use-vaping-is increasingly popular. Various product factors may influence an individual's choice of e-cigarette. To provide an evidence base for e-cigarette regulation, a better understanding of the role different product attributes play in product preferences is needed. Here, we used conjoint analysis to quantify different factors that influence e-cigarettes choices, including flavors, nicotine level, customizability, or use of e-cigarettes to manage appetite/food craving. Young adults completed a set of choice-based conjoint tasks online. Choice Based Conjoint analysis (CBC) was used to determine utility scores for each attribute. Young adults (n = 587) who vaped at least once per week were included in analyses; gender differences were explored. Flavor was the most important attribute (48.1%), followed by product messaging (21.0%) and nicotine level (15.3%). Within flavor, confectionery and fruit flavors had the highest utility scores, while classic menthol and tobacco flavors had the lowest. Men and women differed in flavors, nicotine levels, and product messaging that appealed most. Among young adults who vape weekly, flavor is the most important factor in e-cigarette preferences. Gender also factors into e-cigarette preferences, especially for preferred nicotine level. Understanding why individuals choose particular e-cigarette products will help inform public health efforts and policy making.

Rickettsia honei Infection in a Traveler Returning From India.

We report a case of Rickettsia honei infection in a US tourist returning from India and the Himalayas. This case highlights a need for awareness of various Rickettsia species endemic to India and the importance for physicians to consider rickettsial diseases in returning travelers with eschar or rash-associated febrile illnesses.

The feasibility of an in-scanner smoking lapse paradigm to examine the neural correlates of lapses.

Quitting smoking is notoriously difficult. Models of nicotine dependence posit that strength of cognitive control contributes to maintaining smoking abstinence during smoking cessation attempts. We examine the role for large-scale functional brain systems associated with cognitive control in smoking lapse using a novel adaption of a well-validated behavioral paradigm. We use data from 17 daily smokers (five females) after 12 h of smoking abstinence. Participants completed up to 10 sequential 5-min functional magnetic resonance imaging (fMRI) runs, within a single scanning session. After each run, participants decided whether to stay in the scanner in order to earn additional money or to terminate the session in order to smoke a cigarette (i.e., lapse) and forego additional monetary reward. Cox regression results indicate that decreased segregation of the default mode system from the frontoparietal system undermines the ability to resist smoking. This study demonstrates the feasibility of modifying an established behavioral model of smoking lapse behavior for use in the neuro imaging environment, and it provides initial evidence that this approach yields valuable information regarding fine-grained, time-varying changes in patterns of neural activity in the moments leading up to a decision to smoke. Specifically, results lend support to the hypothesis that the time-varying interplay between large-scale functional brain systems associated with cognitive control is implicated in smoking lapse behavior.

Very Light Daily Smoking in Young Adults: Relationships Between Nicotine Dependence and Lapse.

INTRODUCTION: Very light daily smoking is increasingly common among young adults. Evidence suggests that levels of nicotine dependence vary significantly among young adults who engage in very light daily smoking. However, the links between dependence and clinically relevant outcomes (eg, lapse) in this population remain unclear. The goal of this study was to address this gap by evaluating how well different nicotine dependence scales predict lapse behavior among very light daily smoking young adults. AIMS AND METHODS: Very light daily smokers (1-5 cigarettes/day) aged 18-25 participated in an initial laboratory session, during which nicotine dependence was assessed using four commonly used measures: the FagerstrÓ§m Test for Cigarette Dependence (FTCD), the Hooked On Nicotine Checklist (HONC), the Transdisciplinary Tobacco Use Research Centers (TTURC) Nicotine Dependence Inventory, and the Wisconsin Inventory of Smoking Dependence Motives (WISDM). After a baseline period, eligible participants (n = 40) completed a 10-day abstinence incentive period in which they attempted to refrain from smoking to earn monetary rewards. Cox proportional hazards models were used to test whether dependence predicted days to first lapse. RESULTS: FTCD scores significantly predicted days to lapse, as did scores on the FTCD item assessing time to first cigarette of the day (TTFC). No other dependence measures predicted time to lapse. Both the FTCD and TTFC continued to independently predict time to lapse after controlling for smoking frequency and duration. CONCLUSIONS: The FTCD may be a particularly useful tool for capturing clinically meaningful variability in nicotine dependence among young adults who engage in very light daily smoking. IMPLICATIONS: This is the first study to directly link self-reported nicotine dependence with the ability to achieve and maintain abstinence among very light daily smoking young adults. The results may aid clinicians in selecting among variable measures of nicotine dependence when assessing and treating this population.

X-ray inactivation of RNA viruses without loss of biological characteristics.

In the event of an unpredictable viral outbreak requiring high/maximum biosafety containment facilities (i.e. BSL3 and BSL4), X-ray irradiation has the potential to relieve pressures on conventional diagnostic bottlenecks and expediate work at lower containment. Guided by Monte Carlo modelling and in vitro 1-log10 decimal-reduction value (D-value) predictions, the X-ray photon energies required for the effective inactivation of zoonotic viruses belonging to the medically important families of Flaviviridae, Nairoviridae, Phenuiviridae and Togaviridae are demonstrated. Specifically, it is shown that an optimized irradiation approach is attractive for use in a multitude of downstream detection and functional assays, as it preserves key biochemical and immunological properties. This study provides evidence that X-ray irradiation can support emergency preparedness, outbreak response and front-line diagnostics in a safe, reproducible and scalable manner pertinent to operations that are otherwise restricted to higher containment BSL3 or BSL4 laboratories.