Adaptive learning from outcome contingencies in eating-disorder risk groups.

Eating disorders are characterised by altered eating patterns alongside overvaluation of body weight or shape, and have relatively low rates of successful treatment and recovery. Notably, cognitive inflexibility has been implicated in both the development and maintenance of eating disorders, and understanding the reasons for this inflexibility might indicate avenues for treatment development. We therefore investigate one potential cause of this inflexibility: an inability to adjust learning when outcome contingencies change. We recruited (n = 82) three groups of participants: those who had recovered from anorexia nervosa (RA), those who had high levels of eating disorder symptoms but no formal diagnosis (EA), and control participants (HC). They performed a reinforcement learning task (alongside eye-tracking) in which the volatility of wins and losses was independently manipulated. We predicted that both the RA and EA groups would adjust their learning rates less than the control participants. Unexpectedly, the RA group showed elevated adjustment of learning rates for both win and loss outcomes compared to control participants. The RA group also showed increased pupil dilation to stable wins and reduced pupil dilation to stable losses. Their learning rate adjustment was associated with the difference between their pupil dilation to volatile vs. stable wins. In conclusion, we find evidence that learning rate adjustment is unexpectedly higher in those who have recovered from anorexia nervosa, indicating that the relationship between eating disorders and cognitive inflexibility may be complex. Given our findings, investigation of noradrenergic agents may be valuable in the field of eating disorders.

HER2 amplification by next-generation sequencing to identify HER2-positive invasive breast cancer with negative HER2 immunohistochemistry.

BACKGROUND: Human epidermal growth factor receptor 2 (HER2) positive breast carcinomas due to HER2 amplification are associated with aggressive behavior and a poor prognosis. Anti-HER2-targeted therapies are widely used to treat HER2-positive breast carcinomas with excellent outcomes. Accurate identification of HER2 amplification status in breast carcinomas is of important diagnostic and treatment value. Currently, HER2 amplification status is routinely determined by immunohistochemistry (IHC) and/or fluorescence in situ hybridization (FISH) testing. This study will review our past HER2 data to determine and characterize discordant results between HER2 IHC and FISH. It will also determine a potential impact of HER2 amplification status by next-generation sequencing (NGS) on these patients. METHODS: We reviewed a total of 4884 breast carcinomas with coexisting HER2 IHC and HER2 FISH performed at our institution from 2010 to 2022. 57 cases also had a Next-Generation-Sequencing-based (NGS) gene panel performed. Given the advances in biostatic analysis pipelines, NGS methods were utilized to provide results on HER2 amplification status along with somatic mutations. RESULTS: While the majority (ranging from 98.5% with IHC score of 0 and 93.1% with IHC score of 1 +) of 4884 breast carcinomas had concordant results from HER2 IHC and HER2 FISH testing, a small percentage of patients (ranging from 1.5% in those with IHC score of 0, to 6.9% with IHC score of 1 +) had discordant results, with negative HER2 IHC and positive HER2 FISH results. These patients could be reported as HER2-negative breast carcinomas if only HER2 IHC testing has been performed according to a current cost-effective HER2 test strategy. 57 patients had HER2 amplification status determined by NGS, and all patients had concordant results between HER2 NGS and FISH tests. A HER2-amplified breast carcinoma by NGS had a negative IHC and a positive HER2 FISH result. This case was classified as a HER2-positive breast carcinoma, had anti-HER2-targeted therapy, and achieved a complete clinical response. CONCLUSIONS: A small percentage of HER2-positive breast carcinomas are unidentified because of a negative HER2 IHC based on our current cost-effective HER2 test strategy. It is not feasible and affordable in routine clinical practice to perform HER2 FISH for the cases with negative HER2 IHC (IHC score 0 and 1 +). Therefore, NGS assays capable of simultaneously detecting both somatic mutations and HER2 amplification could provide a more comprehensive genetic profiling for breast carcinomas in a clinical setting. Identification of HER2 amplification by NGS in HER2-positive breast carcinomas with negative HER2 IHC results is important since these cases are concealed by our current cost-effective HER2 test strategy with IHC first (for all cases) and FISH reflex (only for cases with IHC score of 2 +), and would offer the opportunity for potentially beneficial anti-HER2-targeted therapies for these patients.

A Longitudinal Magnetoencephalographic Study of the Effects of Deep Brain Stimulation on Neuronal Dynamics in Severe Anorexia Nervosa.

Anorexia Nervosa (AN) is a debilitating psychiatric disorder characterized by the relentless pursuit of thinness, leading to severe emaciation. Magnetoencephalography (MEG)was used to record the neuronal response in seven patients with treatment-resistant AN while completing a disorder-relevant food wanting task. The patients underwent a 15-month protocol, where MEG scans were conducted pre-operatively, post-operatively prior to deep brain stimulation (DBS) switch on, twice during a blind on/off month and at protocol end. Electrodes were implanted bilaterally into the nucleus accumbens with stimulation at the anterior limb of the internal capsule using rechargeable implantable pulse generators. Three patients met criteria as responders at 12 months of stimulation, showing reductions of eating disorder psychopathology of over 35%. An increase in alpha power, as well as evoked power at latencies typically associated with visual processing, working memory, and contextual integration was observed in ON compared to OFF sessions across all seven patients. Moreover, an increase in evoked power at P600-like latencies as well as an increase in γ-band phase-locking over anterior-to-posterior regions were observed for high- compared to low-calorie food image only in ON sessions. These findings indicate that DBS modulates neuronal process in regions far outside the stimulation target site and at latencies possibly reflecting task specific processing, thereby providing further evidence that deep brain stimulation can play a role in the treatment of otherwise intractable psychiatric disorders.

Deep Brain Stimulation of the Nucleus Accumbens in Severe Enduring Anorexia Nervosa: A Pilot Study.

Introduction: Anorexia nervosa (AN) is one of the most debilitating psychiatric disorders, becoming severe and enduring in a third of cases; with few effective treatments. Deep brain stimulation is a reversible, adjustable neurosurgical procedure that has been gaining ground in psychiatry as a treatment for depression and obsessive-compulsive disorder, yet few studies have investigated AN. Abnormal eating behavior and the compulsive pursuit of thinness in AN is, in part, a consequence of dysfunction in reward circuitry and the nucleus accumbens (NAcc) is central to reward processing. Methods: Phase 1 prospective open-label pilot study of seven individuals with severe enduring AN. Electrodes were implanted bilaterally into the NAcc with stimulation at the anterior limb of the internal capsule using rechargeable implantable pulse generators. The protocol of 15 months included 12 months of deep brain stimulation incorporating two consecutive, randomized blind on-off fortnights 9 months after stimulation onset. The primary objectives were to investigate safety and feasibility, together with changes in eating disorder psychopathology. Results: Feasibility and safety was demonstrated with no serious adverse events due to deep brain stimulation. Three patients responded to treatment [defined as > 35% reduction in Eating Disorders Examination (EDE) score at 12 months] and four patients were non-responders. Responders had a statistically significant mean reduction in EDE scores (50.3% reduction; 95% CI 2.6-98.2%), Clinical Impairment Assessment (45.6% reduction; 95% CI 7.4-83.7%). Responders also had a statistically significant mean reduction in Hamilton Depression Scale, Hamilton Anxiety Scale and Snaith-Hamilton pleasure scale. There were no statistically significant changes in Body Mass Index, Yale-Brown-Cornell Eating Disorder Scale, Yale-Brown Obsessive-Compulsive Scale and World Health Organization Quality of Life Psychological subscale. Conclusion: This study provides some preliminary indication that deep brain stimulation to the NAcc. Might potentially improve some key features of enduring AN. In this small study, the three responders had comorbid obsessive-compulsive disorder which predated AN diagnosis. Future studies should aim to further elucidate predictors of outcome. Clinical Trial Registration: [www.ClinicalTrials.gov], identifier [Project ID 128658].

Study Protocol for "Psilocybin as a Treatment for Anorexia Nervosa: A Pilot Study".

Background: Anorexia nervosa (AN) is a serious and life-threatening psychiatric condition. With a paucity of approved treatments, there is a desperate need for novel treatment avenues to be explored. Here, we present (1) an overview of the ways through which Public Patient Involvement (PPI) has informed a trial of psilocybin-assisted therapy for AN and (2) a protocol for a pilot study of psilocybin-assisted therapy in AN currently underway at Imperial College London. The study aims to assess the feasibility, brain mechanisms and preliminary outcomes of treating anorexia nervosa with psilocybin. Methods: (1) PPI: Across two online focus groups, eleven individuals with lived experience of AN were presented with an overview of the protocol. Their feedback not only identified solutions to possible barriers for future participants, but also helped the research team to better understand the concept of "recovery" from the perspective of those with lived experience. (2) Protocol: Twenty female participants [21-65 years old, body mass index (BMI) 15 kg/m2 or above] will receive three oral doses of psilocybin (up to 25 mg) over a 6-week period delivered in a therapeutic environment and enveloped by psychological preparation and integration. We will work with participant support networks (care teams and an identified support person) throughout and there will be an extended remote follow-up period of 12 months. Our two-fold primary outcomes are (1) psychopathology (Eating Disorder Examination) across the 6-month follow-up and (2) readiness and motivation to engage in recovery (Readiness and Motivation Questionnaire) across the 6-week trial period. Neurophysiological outcome measures will be: (1) functional magnetic resonance imaging (fMRI) brain changes from baseline to 6-week endpoint and (2) post-acute changes in electroencephalography (EEG) activity, including an electrophysiological marker of neuronal plasticity. Discussion: The results of this pilot study will not only shed light on the acceptability, brain mechanisms, and impression of the potential efficacy of psilocybin as an adjunct treatment for AN but will be essential in shaping a subsequent Randomised Control Trial (RCT) that would test this treatment against a suitable control condition. Clinical Trial Registration: identifier: NCT04505189.

Clinical Utility of Targeted Next-Generation Sequencing Assay to Detect Copy Number Variants Associated with Myelodysplastic Syndrome in Myeloid Malignancies.

Copy number variants (CNVs) and gene mutations are important for diagnosis and treatment of myeloid malignancies. In a routine clinical setting, somatic gene mutations are detected by targeted next-generation sequencing (NGS) assay, but CNVs are commonly detected by conventional chromosome analysis and fluorescence in situ hybridization (FISH). The aim of this proof-of-principle study was to investigate the feasibility of using targeted NGS to simultaneously detect both somatic mutations and CNVs. Herein, we sequenced 406 consecutive patients with myeloid malignancies by targeted NGS and performed a head-to-head comparison with the results from a myelodysplastic syndrome (MDS) FISH and conventional chromosome analysis to detect CNVs. Among 91 patients with abnormal MDS FISH results, the targeted NGS revealed all 120 CNVs detected by MDS FISH (including -5/5q-, -7/7q-, +8, and 20q-) and 193 extra CNVs detected by conventional chromosome analysis. The targeted NGS achieved 100% concordance with the MDS FISH. The lower limit of detection of MDS CNVs by the targeted NGS was generally 5% variant allele fraction for DNA, based on the lowest percentages of abnormal cells detected by MDS FISH in this study. This proof-of-principle study demonstrated that the targeted NGS assay can simultaneously detect both MDS CNVs and somatic mutations, which can provide a more comprehensive genetic profiling for patients with myeloid malignancies using a single assay in a clinical setting.

Brief Report: Lower Socioeconomic Status Associates With Greater Systemic and Arterial Inflammation in HIV.

OBJECTIVES: In the general population, the lower socioeconomic status (SES) associates with greater systemic and arterial inflammation and a greater risk of cardiovascular disease. Because arterial inflammation is heightened in individuals living with HIV, we tested the hypothesis that SES associates with arterial inflammation in this population. SETTINGS: Prospective cohort study. METHODS: Men living with HIV were recruited. Arterial inflammation and leukopoietic activity (ie, bone marrow activity) were measured using 18F-fluorodeoxyglucose positron emission tomography/computed tomography. Zip code-level SES measures were derived from the US Census Bureau. Linear regression and mediation analyses were used to assess associations between SES, arterial inflammation, leukopoietic activity, C-reactive protein (CRP), and interleukin-6. RESULTS: Thirty-nine virologically suppressed men living with HIV were studied (mean ± SD age 50.5 ± 11.1 years). The median CD4 count was 663 cells/mm3 (interquartile range: 399-922); 82% were receiving antiretroviral therapies. Local median income inversely associated with arterial inflammation [standardized ß (95% confidence interval): -0.42 (-0.76 to -0.08)] after adjusting for age, Framingham risk score, statin use, antiretroviral use, and nadir CD4 count. The high-school graduation rate independently associated with arterial inflammation [-0.45 (-0.78 to -0.12)] and CRP [-0.49 (-0.86 to -0.012)]. Mediation analysis demonstrated the impact of SES on arterial inflammation was partially mediated by heightened circulating inflammatory levels: ↓SES (as high school graduation rate) →↑CRP →↑arterial inflammation accounting for 44% of the total effect (P < 0.05). CONCLUSION: In individuals living with HIV, lower SES independently associated with higher leukopoietic activity, circulating markers of inflammation, and arterial inflammation. Furthermore, the link between SES and arterial inflammation was mediated by increased systemic inflammation.

The Role of Interoception in the Pathogenesis and Treatment of Anorexia Nervosa: A Narrative Review.

Anorexia nervosa (AN) is a psychiatric illness characterized by extreme overvaluation of weight and disturbed eating. Despite having the highest mortality rate of any psychiatric illness, the etiology and neurobiology of AN are poorly understood. A growing body of research has begun to elucidate the role of reward processing, as well as cognitive and limbic networks, in the symptomology of AN. However, these advances have so far failed to contribute therapeutically, suggesting a new understanding may be necessary. A disturbance in the interoceptive system, involved in perceiving and interpreting the physiological condition of the body, has recently been proposed as a central mechanism of pathology in AN, through links to hunger and satiety, risk prediction errors, emotional awareness, and body dysmorphia. This review summarizes the existing literature in order to clarify possible underlying mechanisms and proposes a novel model of the neuro-circuitry of AN. Detailed neuroanatomical studies and new methods for studying interoception may allow further refinement of this model and the development of improved treatment.

Does repeatedly viewing overweight versus underweight images change perception of and satisfaction with own body size?

Body dissatisfaction is associated with subsequent eating disorders and weight gain. One-off exposure to bodies of different sizes changes perception of others' bodies, and perception of and satisfaction with own body size. The effect of repeated exposure to bodies of different sizes has not been assessed. We randomized women into three groups, and they spent 5 min twice a day for a week completing a one-back task using images of women modified to appear either under, over, or neither over- nor underweight. We tested the effects on their perception of their own and others' body size, and satisfaction with own size. Measures at follow-up were compared between groups, adjusted for baseline measurements. In 93 women aged 18-30 years, images of other women were perceived as larger following exposure to underweight women (and vice versa) (p < 0.001). There was no evidence for a difference in our primary outcome measure (visual analogue scale own size) or in satisfaction with own size. Avatar-constructed ideal (p = 0.03) and avatar-constructed perceived own body size (p = 0.007) both decreased following exposure to underweight women, possibly due to adaptation affecting how the avatar was perceived. Repeated exposure to different sized bodies changes perception of the size of others' bodies, but we did not find evidence that it changes perceived own size.

Psychological Treatments for People With Severe and Enduring Anorexia Nervosa: A Mini Review.

This Mini-Review presents recent research into evidence for psychological treatments for people with severe and enduring anorexia nervosa (SEAN). Two psychological therapies, specialist supportive clinical management (SSCM), and cognitive behavior therapy for anorexia nervosa (CBT-AN) have limited (one randomized controlled study) evidence of efficacy. Both have had adaptations for SEAN, notably with revision of the primary treatment goal of improved quality of life and full weight recovery a secondary goal. A major issue with existing studies is poor definition of SEAN, and the large deficit in research that has used an agreed definition of SEAN. In particular, it may be problematic to extrapolate from studies of people with either severe and/or enduring but not intractable or "resistant" illness. People with longstanding AN who have not received evidence based care should be offered this with an expectation of recovery. Similarly, people with SEAN may be offered care with judicious mitigation of expectations. In the future, trials should include people with SEAN clearly defined. Trials with a subsample of participants likely to have SEAN, if identified at randomisation, are an opportunity for secondary analyses of such participants. This would widen the evidence base for psychological treatments providing hope for people with this devastating illness. Finally, there is an urgent need not only to strengthen our existing knowledge with studies of sufficient power, but also, fundamentally, to derive novel conceptualizations of what "treatment" involves.

The Gut Microbiome in Anorexia Nervosa: Friend or Foe?

The human gut microbiome is emerging as a key modulator of homeostasis, with far-reaching implications for various multifactorial diseases, including anorexia nervosa (AN). Despite significant morbidity and mortality, the underlying mechanisms of this eating disorder are poorly understood, but the classical view defining AN as a purely psychiatric condition is increasingly being challenged. Accumulating evidence from comparative studies of AN and healthy fecal microbial composition reveals considerable low divergence and altered taxonomic abundance of the AN gut microbiome. When integrated with preclinical data, these findings point to a significant role of the gut microbiome in AN pathophysiology, via effects on host energy metabolism, intestinal permeability, immune function, appetite, and behavior. While complex causal relationships between genetic risk factors, dietary patterns and microbiome, and their relevance for AN onset and perpetuation have not been fully elucidated, preliminary clinical studies support the use of microbiome-based interventions such as fecal microbiota transplants and probiotics as adjuvants to standard AN therapies. Future research should aim to move from observational to mechanistic, as dissecting how specific microbial taxa interact with the host to impact the development of AN could help design novel therapeutic approaches that more effectively address the severe comorbidities and high relapse rate of this serious disorder.

Low-Temperature Side Contact to Carbon Nanotube Transistors: Resistance Distributions Down to 10 nm Contact Length.

Carbon nanotube field-effect transistors (CNFETs) promise to improve the energy efficiency, speed, and transistor density of very large scale integration circuits owing to the intrinsic thin channel body and excellent charge transport properties of carbon nanotubes. Low-temperature fabrication (e.g., <400 °C) is a key enabler for the monolithic three-dimensional (3D) integration of CNFET digital logic into a device technology platform that overcomes memory bandwidth bottlenecks for data-abundant applications such as big-data analytics and machine learning. However, high contact resistance for short CNFET contacts has been a major roadblock to establishing CNFETs as a viable technology because the contact resistance, in series with the channel resistance, reduces the on-state current of CNFETs. Additionally, the variation in contact resistance remains unstudied for short contacts and will further degrade the energy efficiency and speed of CNFET circuits. In this work, we investigate by experiments the contact resistance and statistical variation of room-temperature fabricated CNFET contacts down to 10 nm contact lengths. These CNFET contacts are ∼15 nm shorter than the state-of-the-art Si CMOS "7 nm node" contact length, allowing for multiple generations of future scaling of the transistor-contacted gate pitch. For the 10 nm contacts, we report contact resistance values down to 6.5 kΩ per source/drain contact for a single carbon nanotube (CNT) with a median contact resistance of 18.2 kΩ. The 10 nm contacts reduce the CNFET current by as little as 13% at VDS = 0.7 V compared with the best reported 200 nm contacts to date, corroborated by results in this work. Our analysis of RC from 232 single-CNT CNFETs between the long-contact (e.g., 200 nm) and short-contact (e.g., 10 nm) regimes quantifies the resistance variation and projects the impact on CNFET current variability versus the number of CNT in the transistor. The resistance distribution reveals contact-length-dependent RC variations become significant below 20 nm contact length. However, a larger source of CNFET resistance variation is apparent at all contact lengths used in this work. To further investigate the origins of this contact-length-independent resistance variation, we analyze the variation of RC in arrays of identical CNFETs along a single CNT of constant diameter and observe the random occurrence of high  RC, even on correlated CNFETs.

The Moral Obligation to Prioritize Research Into Deep Brain Stimulation Over Brain Lesioning Procedures for Severe Enduring Anorexia Nervosa.

Deep Brain Stimulation is currently being investigated as an experimental treatment for patients suffering from treatment-refractory AN, with an increasing number of case reports and small-scale trials published. Although still at an exploratory and experimental stage, initial results have been promising. Despite the risks associated with an invasive neurosurgical procedure and the long-term implantation of a foreign body, DBS has a number of advantageous features for patients with SE-AN. Stimulation can be fine-tuned to the specific needs of the particular patient, is relatively reversible, and the technique also allows for the crucial issue of investigating and comparing the effects of different neural targets. However, at a time when DBS is emerging as a promising investigational treatment modality for AN, lesioning procedures in psychiatry are having a renaissance. Of concern it has been argued that the two kinds of interventions should instead be understood as rivaling, yet "mutually enriching paradigms" despite the fact that lesioning the brain is irreversible and there is no evidence base for an effective target in AN. We argue that lesioning procedures in AN are unethical at this stage of knowledge and seriously problematic for this patient group, for whom self-control is particularly central to wellbeing. They pose a greater risk of major harms that cannot justify ethical equipoise, despite the apparent superiority in reduced short term surgical harms and lower cost.

Effects of exposure to bodies of different sizes on perception of and satisfaction with own body size: two randomized studies.

Body dissatisfaction is prevalent among women and associated with subsequent obesity and eating disorders. Exposure to images of bodies of different sizes has been suggested to change the perception of 'normal' body size in others. We tested whether exposure to different-sized (otherwise identical) bodies changes perception of own and others' body size, satisfaction with body size and amount of chocolate consumed. In Study 1, 90 18-25-year-old women with normal BMI were randomized into one of three groups to complete a 15 min two-back task using photographs of women either of 'normal weight' (Body Mass Index (BMI) 22-23 kg m-2), or altered to appear either under- or over-weight. Study 2 was identical except the 96 participants had high baseline body dissatisfaction and were followed up after 24 h. We also conducted a mega-analysis combining both studies. Participants rated size of others' bodies, own size, and satisfaction with size pre- and post-task. Post-task ratings were compared between groups, adjusting for pre-task ratings. Participants exposed to over- or normal-weight images subsequently perceived others' bodies as smaller, in comparison to those shown underweight bodies (p < 0.001). They also perceived their own bodies as smaller (Study 1, p = 0.073; Study 2, p = 0.018; mega-analysis, p = 0.001), and felt more satisfied with their size (Study 1, p = 0.046; Study 2, p = 0.004; mega-analysis, p = 0.006). There were no differences in chocolate consumption. This study suggests that a move towards using images of women with a BMI in the healthy range in the media may help to reduce body dissatisfaction, and the associated risk of eating disorders.

Study Protocol: Using Deep-Brain Stimulation, Multimodal Neuroimaging and Neuroethics to Understand and Treat Severe Enduring Anorexia Nervosa.

BACKGROUND: Research suggests that altered eating and the pursuit of thinness in anorexia nervosa (AN) are, in part, a consequence of aberrant reward circuitry. The neural circuits involved in reward processing and compulsivity overlap significantly, and this has been suggested as a transdiagnostic factor underpinning obsessive compulsive disorder, addictions and eating disorders. The nucleus accumbens (NAcc) is central to both reward processing and compulsivity. In previous studies, deep-brain stimulation (DBS) to the NAcc has been shown to result in neural and symptomatic improvement in both obsessive compulsive disorder and addictions. Moreover, in rats, DBS to the NAcc medial shell increases food intake. We hypothesise that this treatment may be of benefit in severe and enduring anorexia nervosa (SE-AN), but first, feasibility and ethical standards need to be established. The aims of this study are as follows: (1) to provide feasibility and preliminary efficacy data on DBS to the NAcc as a treatment for SE-AN; (2) to assess any subsequent neural changes and (3) to develop a neuroethical gold standard to guide applications of this treatment. METHOD: This is a longitudinal study of six individuals with SE-AN of >7 years. It includes an integrated neuroethical sub-study. DBS will be applied to the NAcc and we will track the mechanisms underpinning AN using magnetoelectroencephalography, neuropsychological and behavioural measures. Serial measures will be taken on each intensively studied patient, pre- and post-DBS system insertion. This will allow elucidation of the processes involved in symptomatic change over a 15-month period, which includes a double-blind crossover phase of stimulator on/off. DISCUSSION: Novel, empirical treatments for SE-AN are urgently required due to high morbidity and mortality costs. If feasible and effective, DBS to the NAcc could be game-changing in the management of this condition. A neuroethical gold standard is crucial to optimally underpin such treatment development. CLINICAL TRIAL REGISTRATION: The study is ongoing and registered with www.ClinicalTrials.gov, https://clinicaltrials.gov/ct2/show/NCT01924598, 22 July, 2013. It has full ethical and HRA approval (Project ID 128658).

Three-dimensional integration of nanotechnologies for computing and data storage on a single chip.

The computing demands of future data-intensive applications will greatly exceed the capabilities of current electronics, and are unlikely to be met by isolated improvements in transistors, data storage technologies or integrated circuit architectures alone. Instead, transformative nanosystems, which use new nanotechnologies to simultaneously realize improved devices and new integrated circuit architectures, are required. Here we present a prototype of such a transformative nanosystem. It consists of more than one million resistive random-access memory cells and more than two million carbon-nanotube field-effect transistors-promising new nanotechnologies for use in energy-efficient digital logic circuits and for dense data storage-fabricated on vertically stacked layers in a single chip. Unlike conventional integrated circuit architectures, the layered fabrication realizes a three-dimensional integrated circuit architecture with fine-grained and dense vertical connectivity between layers of computing, data storage, and input and output (in this instance, sensing). As a result, our nanosystem can capture massive amounts of data every second, store it directly on-chip, perform in situ processing of the captured data, and produce 'highly processed' information. As a working prototype, our nanosystem senses and classifies ambient gases. Furthermore, because the layers are fabricated on top of silicon logic circuitry, our nanosystem is compatible with existing infrastructure for silicon-based technologies. Such complex nano-electronic systems will be essential for future high-performance and highly energy-efficient electronic systems.

Hysteresis-Free Carbon Nanotube Field-Effect Transistors.

While carbon nanotube (CNT) field-effect transistors (CNFETs) promise high-performance and energy-efficient digital systems, large hysteresis degrades these potential CNFET benefits. As hysteresis is caused by traps surrounding the CNTs, previous works have shown that clean interfaces that are free of traps are important to minimize hysteresis. Our previous findings on the sources and physics of hysteresis in CNFETs enabled us to understand the influence of gate dielectric scaling on hysteresis. To begin with, we validate through simulations how scaling the gate dielectric thickness results in greater-than-expected benefits in reducing hysteresis. Leveraging this insight, we experimentally demonstrate reducing hysteresis to <0.5% of the gate-source voltage sweep range using a very large-scale integration compatible and solid-state technology, simply by fabricating CNFETs with a thin effective oxide thickness of 1.6 nm. However, even with negligible hysteresis, large subthreshold swing is still observed in the CNFETs with multiple CNTs per transistor. We show that the cause of large subthreshold swing is due to threshold voltage variation between individual CNTs. We also show that the source of this threshold voltage variation is not explained solely by variations in CNT diameters (as is often ascribed). Rather, other factors unrelated to the CNTs themselves (i.e., process variations, random fixed charges at interfaces) are a significant factor in CNT threshold voltage variations and thus need to be further improved.

Reduced Resting-State Functional Connectivity in Current and Recovered Restrictive Anorexia Nervosa.

Functional connectivity studies based on resting-state functional magnetic resonance imaging (rs-fMRI) have shown alterations in brain networks associated with self-referential processing, cognitive control, and somatosensory processing in anorexia nervosa (AN). This study aimed to further investigate the functional connectivity of resting-state networks (RSNs) in homogenous subsamples of individuals with restrictive AN (current and recovered) and the relationship this has with core eating disorder psychopathology. rs-fMRI scans were obtained from 12 female individuals with restrictive AN, 14 females recovered from restrictive AN, and 16 female healthy controls. Independent components analysis revealed a set of functionally relevant RSNs, previously reported in the literature. Dual regression analysis showed decreased temporal coherence within the lateral visual and auditory RSNs in individuals with current AN and those recovered from AN compared to healthy individuals. This decreased connectivity was also found in regions associated with somatosensory processing, and is consistent with reduced interoceptive awareness and body image perception, characteristic of AN. Widespread gray matter (GM) reductions were also found in both the AN groups, and differences in functional connectivity were no longer significant when GM maps were added as a covariate in the dual regression analysis. This raises the possibility that deficits in somatosensory and interoceptive processing observed in AN may be in part underpinned or exacerbated by GM reductions.