Multiplexed, High Density Electrophysiology with Nanofabricated Neural Probes

Extracellular electrode arrays can reveal the neuronal network correlates of behavior with single-cell, single-spike, and sub-millisecond resolution. However, implantable electrodes are inherently invasive, and efforts to scale up the number and density of recording sites must compromise on device size in order to connect the electrodes. Here, we report on silicon-based neural probes employing nanofabricated, high-density electrical leads. Furthermore, we address the challenge of reading out multichannel data with an application-specific integrated circuit (ASIC) performing signal amplification, band-pass filtering, and multiplexing functions. We demonstrate high spatial resolution extracellular measurements with a fully integrated, low noise 64-channel system weighing just 330 mg. The on-chip multiplexers make possible recordings with substantially fewer external wires than the number of input channels. By combining nanofabricated probes with ASICs we have implemented a system for performing large-scale, high-density electrophysiology in small, freely behaving animals that is both minimally invasive and highly scalable

Kondo physics in carbon nanotubes

The connection of electrical leads to wire-like molecules is a logical step in the development of molecular electronics, but also allows studies of fundamental physics. For example, metallic carbon nanotubes are quantum wires that have been found to act as one-dimensional quantum dots, Luttinger-liquids, proximity-induced superconductors and ballistic and diffusive one-dimensional metals. Here we report that electrically-contacted single-wall nanotubes can serve as powerful probes of Kondo physics, demonstrating the universality of the Kondo effect. Arising in the prototypical case from the interaction between a localized impurity magnetic moment and delocalized electrons in a metallic host, the Kondo effect has been used to explain enhanced low-temperature scattering from magnetic impurities in metals, and also occurs in transport through semiconductor quantum dots. The far higher tunability of dots (in our case, nanotubes) compared with atomic impurities renders new classes of Kondo-like effects accessible. Our nanotube devices differ from previous systems in which Kondo effects have been observed, in that they are one-dimensional quantum dots with three-dimensional metal (gold) reservoirs. This allows us to observe Kondo resonances for very large electron number (N) in the dot, and approaching the unitary limit (where the transmission reaches its maximum possible value). Moreover, we detect a previously unobserved Kondo effect, occurring for even values of N in a magnetic field.Comment: 7 pages, pdf onl

The role of rigidity in adaptive and maladaptive families assessed by FACES IV: the points of view of adolescents

Previous studies using Olson’s Circumplex Model and FACES IV, the self-report assessing family functioning, did not clarify the role of rigidity, a dimension of this model. Rigidity emerged as ambiguous: it was considered either as a functional or as a dysfunctional dimension. Building upon the results of previous studies, we provided a contribution intended to disambiguate the role of rigidity considering adolescents’ perceptions and using a non-a priori classification analysis. 320 Italian adolescents (13–21 years) participated in this study and responded to a questionnaire containing scales of the study variables. A latent class analysis was performed to identify the association of rigidity with the other dimensions of Olson’s model and with indicators of adaptive family functioning in adolescence: parental monitoring and family satisfaction. We found six clusters corresponding to family typologies and having different levels of functioning. Rigidity emerged as adaptive in the typologies named rigidly balanced and flexibly oscillating; it was associated with positive dimensions of family functioning, i.e. flexibility, cohesion, parental monitoring, and high levels of family satisfaction. Differently, when rigidity was associated with disengagement, low cohesion and flexibility, and lack of parental supervision, emerged as maladaptive. This was the case of two typologies: the rigidly disengaged and the chaotically disengaged. Adolescents of these families reported the lowest levels of satisfaction. In the two last typologies, the flexibly chaotic and the cohesively disorganized, rigidity indicated a mid-range functionality as these families were characterized by emotional connectedness but lack of containment. Clinical implications are discussed

Pain and analgesic use associated with skeletal-related events in patients with advanced cancer and bone metastases

PURPOSE: Bone metastases secondary to solid tumors increase the risk of skeletal-related events (SREs), including the occurrence of pathological fracture (PF), radiation to bone (RB), surgery to bone (SB), and spinal cord compression (SCC). The aim of this study was to evaluate the impact of SREs on patients' pain, analgesic use, and pain interference with daily functioning. METHODS: Data were combined from patients with solid tumors and bone metastases who received denosumab or zoledronic acid across three identically designed phase 3 trials (N = 5543). Pain severity (worst pain) and pain interference were assessed using the Brief Pain Inventory at baseline and each monthly visit. Analgesic use was quantified using the Analgesic Quantification Algorithm. RESULTS: The proportion of patients with moderate/severe pain and strong opioid use generally increased in the 6 months preceding an SRE and remained elevated, while they remained relatively consistent over time in patients without an SRE. Regression analysis indicated that all SRE types were significantly associated with an increased risk of progression to moderate/severe pain and strong opioid use. PF, RB, and SCC were associated with significantly greater risk of pain interference overall. Results were similar for pain interference with emotional well-being. All SRE types were associated with significantly greater risk of pain interference with physical function. CONCLUSIONS: SREs are associated with increased pain and analgesic use in patients with bone metastases. Treatments that prevent SREs may decrease pain and the need for opioid analgesics and reduce the impact of pain on daily functioning

Pain and analgesic use associated with skeletal-related events in patients with advanced cancer and bone metastases

PURPOSE: Bone metastases secondary to solid tumors increase the risk of skeletal-related events (SREs), including the occurrence of pathological fracture (PF), radiation to bone (RB), surgery to bone (SB), and spinal cord compression (SCC). The aim of this study was to evaluate the impact of SREs on patients' pain, analgesic use, and pain interference with daily functioning. METHODS: Data were combined from patients with solid tumors and bone metastases who received denosumab or zoledronic acid across three identically designed phase 3 trials (N = 5543). Pain severity (worst pain) and pain interference were assessed using the Brief Pain Inventory at baseline and each monthly visit. Analgesic use was quantified using the Analgesic Quantification Algorithm. RESULTS: The proportion of patients with moderate/severe pain and strong opioid use generally increased in the 6 months preceding an SRE and remained elevated, while they remained relatively consistent over time in patients without an SRE. Regression analysis indicated that all SRE types were significantly associated with an increased risk of progression to moderate/severe pain and strong opioid use. PF, RB, and SCC were associated with significantly greater risk of pain interference overall. Results were similar for pain interference with emotional well-being. All SRE types were associated with significantly greater risk of pain interference with physical function. CONCLUSIONS: SREs are associated with increased pain and analgesic use in patients with bone metastases. Treatments that prevent SREs may decrease pain and the need for opioid analgesics and reduce the impact of pain on daily functioning

Evaluation of anaemia in patients with multiple myeloma and lymphoma: findings of the European CANCER ANAEMIA SURVEY

Birgegård G, Gascón P, Ludwig H. Evaluation of anaemia in patients with multiple myeloma and lymphoma: findings of the European CANCER ANAEMIA SURVEY. Objectives: Until recently, no prospective epidemiologic survey of lymphoma and multiple myeloma (L/MM) in European cancer patients had been conducted; furthermore, data on prevalence, incidence, and treatment patterns of L/MM were limited or unavailable. Here we define anemia prevalence, incidence, and treatment patterns, and identify anemia risk factors in European L/MM patients. Methods: Data for a subgroup of 2360 L/MM patients in the European Cancer Anaemia Survey (ECAS) were analyzed; variables included age, gender, tumor type/stage, cancer and anemia treatment, WHO performance status, and hemoglobin (Hb) levels. Results: 2316 patients were evaluable (1612 L and 704 MM). Anemia rate at enrollment was 52.5%. At enrollment, Hb levels correlated significantly with WHO scores (r = −0.306, P < 0.001). Anemia prevalence during ECAS was 72.9% (MM, 85.3%; non-Hodgkin's lymphoma, 77.9%; Hodgkin's disease, 57.4%); incidence in chemotherapy patients was 55.4%. Only 47.3% of patients anemic any time during ECAS received anemia treatment; overall Hb nadir for initiating treatment was 8.9 g/dL (epoetin, 9.5 g/dL; transfusion, 8.2 g/dL). Factors found to significantly (P < 0.03) increase anemia risk were low initial Hb, female gender, persistent/resistant disease, and platinum chemotherapy. Conclusions:L/MM patients have a high prevalence and incidence of anemia; however, anemia is not optimally treated. Anemia is common in L/MM patients and, given its known adverse impact on physical functioning and quality-of-life variables including fatigue and cognitive function, anemia management should be an integral part of their care. Predictive factors identified by ECAS may help clinicians develop optimal anemia treatment strategies for L/MM patients

Gravity waves and the LHC: Towards high-scale inflation with low-energy SUSY

It has been argued that rather generic features of string-inspired inflationary theories with low-energy supersymmetry (SUSY) make it difficult to achieve inflation with a Hubble scale H > m_{3/2}, where m_{3/2} is the gravitino mass in the SUSY-breaking vacuum state. We present a class of string-inspired supergravity realizations of chaotic inflation where a simple, dynamical mechanism yields hierarchically small scales of post-inflationary supersymmetry breaking. Within these toy models we can easily achieve small ratios between m_{3/2} and the Hubble scale of inflation. This is possible because the expectation value of the superpotential relaxes from large to small values during the course of inflation. However, our toy models do not provide a reasonable fit to cosmological data if one sets the SUSY-breaking scale to m_{3/2} < TeV. Our work is a small step towards relieving the apparent tension between high-scale inflation and low-scale supersymmetry breaking in string compactifications.Comment: 21+1 pages, 5 figures, LaTeX, v2: added references, v3: very minor changes, version to appear in JHE

Visual Cells Remember Earlier Applied Target: Plasticity of Orientation Selectivity

BACKGROUND: A canonical proposition states that, in mature brain, neurons responsive to sensory stimuli are tuned to specific properties installed shortly after birth. It is amply demonstrated that that neurons in adult visual cortex of cats are orientation-selective that is they respond with the highest firing rates to preferred oriented stimuli. METHODOLOGY/PRINCIPAL FINDINGS: In anesthetized cats, prepared in a conventional fashion for single cell recordings, the present investigation shows that presenting a stimulus uninterruptedly at a non-preferred orientation for twelve minutes induces changes in orientation preference. Across all conditions orientation tuning curves were investigated using a trial by trial method. Contrary to what has been previously reported with shorter adaptation duration, twelve minutes of adaptation induces mostly attractive shifts, i.e. toward the adapter. After a recovery period allowing neurons to restore their original orientation tuning curves, we carried out a second adaptation which produced three major results: (1) more frequent attractive shifts, (2) an increase of their magnitude, and (3) an additional enhancement of responses at the new or acquired preferred orientation. Additionally, we also show that the direction of shifts depends on the duration of the adaptation: shorter adaptation in most cases produces repulsive shifts, whereas adaptation exceeding nine minutes results in attractive shifts, in the same unit. Consequently, shifts in preferred orientation depend on the duration of adaptation. CONCLUSION/SIGNIFICANCE: The supplementary response improvements indicate that neurons in area 17 keep a memory trace of the previous stimulus properties, thereby upgrading cellular performance. It also highlights the dynamic nature of basic neuronal properties in adult cortex since repeated adaptations modified both the orientation tuning selectivity and the response strength to the preferred orientation. These enhanced neuronal responses suggest that the range of neuronal plasticity available to the visual system is broader than anticipated

Pain outcomes in patients with bone metastases from advanced cancer: assessment and management with bone-targeting agents

Bone metastases in advanced cancer frequently cause painful complications that impair patient physical activity and negatively affect quality of life. Pain is often underreported and poorly managed in these patients. The most commonly used pain assessment instruments are visual analogue scales, a single-item measure, and the Brief Pain Inventory Questionnaire-Short Form. The World Health Organization analgesic ladder and the Analgesic Quantification Algorithm are used to evaluate analgesic use. Bone-targeting agents, such as denosumab or bisphosphonates, prevent skeletal complications (i.e., radiation to bone, pathologic fractures, surgery to bone, and spinal cord compression) and can also improve pain outcomes in patients with metastatic bone disease. We have reviewed pain outcomes and analgesic use and reported pain data from an integrated analysis of randomized controlled studies of denosumab versus the bisphosphonate zoledronic acid (ZA) in patients with bone metastases from advanced solid tumors. Intravenous bisphosphonates improved pain outcomes in patients with bone metastases from solid tumors. Compared with ZA, denosumab further prevented pain worsening and delayed the need for treatment with strong opioids. In patients with no or mild pain at baseline, denosumab reduced the risk of increasing pain severity and delayed pain worsening along with the time to increased pain interference compared with ZA, suggesting that use of denosumab (with appropriate calcium and vitamin D supplementation) before patients develop bone pain may improve outcomes. These data also support the use of validated pain assessments to optimize treatment and reduce the burden of pain associated with metastatic bone disease

Exoplanets and SETI

The discovery of exoplanets has both focused and expanded the search for extraterrestrial intelligence. The consideration of Earth as an exoplanet, the knowledge of the orbital parameters of individual exoplanets, and our new understanding of the prevalence of exoplanets throughout the galaxy have all altered the search strategies of communication SETI efforts, by inspiring new "Schelling points" (i.e. optimal search strategies for beacons). Future efforts to characterize individual planets photometrically and spectroscopically, with imaging and via transit, will also allow for searches for a variety of technosignatures on their surfaces, in their atmospheres, and in orbit around them. In the near-term, searches for new planetary systems might even turn up free-floating megastructures.Comment: 9 page invited review. v2 adds some references and v3 has other minor additions and modification