Hairlike Percutaneous Photochemical Sensors

Instrumentation systems based on hairlike fiber-optic photochemical sensors have been proposed as minimally invasive means of detecting biochemicals associated with cancer and other diseases. The fiber-optic sensors could be mass-produced as inexpensive, disposable components. The sensory tip of a fiber-optic sensor would be injected through the patient's skin into subcutaneous tissue. A biosensing material on the sensory tip would bind or otherwise react with the biochemical(s) of interest [the analyte(s)] to produce a change in optical properties that would be measured by use of an external photonic analyzer. After use, a fiber-optic sensor could be simply removed by plucking it out with tweezers. A fiber-optic sensor according to the proposal would be of the approximate size and shape of a human hair, and its sensory tip would resemble a follicle. Once inserted into a patient's subcutaneous tissue, the sensor would even more closely resemble a hair growing from a follicle (see Figure 1). The biosensing material on the sensory tip could consist of a chemical and/or cells cultured and modified for the purpose. The biosensing material would be contained within a membrane that would cover the tip. If the membrane were not permeable by an analyte, then it would be necessary to create pores in the membrane that would be large enough to allow analyte molecules to diffuse to the biosensing material, but not so large as to allow cells (if present as part of the biosensing material) to diffuse out. The end of the fiber-optic sensor opposite the sensory tip would be inserted in a fiberoptic socket in the photonic analyzer

Muscle coordination is habitual rather than optimal

When sharing load among multiple muscles, humans appear to select an optimal pattern of activation that minimizes costs such as the effort or variability of movement. How the nervous system achieves this behavior, however, is unknown. Here we show that contrary to predictions from optimal control theory, habitual muscle activation patterns are surprisingly robust to changes in limb biomechanics. We first developed a method to simulate joint forces in real time from electromyographic recordings of the wrist muscles. When the model was altered to simulate the effects of paralyzing a muscle, the subjects simply increased the recruitment of all muscles to accomplish the task, rather than recruiting only the useful muscles. When the model was altered to make the force output of one muscle unusually noisy, the subjects again persisted in recruiting all muscles rather than eliminating the noisy one. Such habitual coordination patterns were also unaffected by real modifications of biomechanics produced by selectively damaging a muscle without affecting sensory feedback. Subjects naturally use different patterns of muscle contraction to produce the same forces in different pronation-supination postures, but when the simulation was based on a posture different from the actual posture, the recruitment patterns tended to agree with the actual rather than the simulated posture. The results appear inconsistent with computation of motor programs by an optimal controller in the brain. Rather, the brain may learn and recall command programs that result in muscle coordination patterns generated by lower sensorimotor circuitry that are functionally "good-enough.

Preventing Ischial Pressure Ulcers: II. Biomechanics

Background: Pressure ulcers (PUs) are common and debilitating wounds that arise when immobilized patients cannot shift their weight. Neuromuscular Electrical Stimulation (NMES) has been investigated for Pressure Ulcer Prevention (PUP) for over 20 years. Historically gluteus maximus (GM) has been considered an important actuator in attempting to redistribute seated pressures through NMES

Longwave Band-by-band Cloud Radiative Effect and its Application in GCM Evaluation

The cloud radiative effect (CRE) of each longwave (LW) absorption band of a GCM fs radiation code is uniquely valuable for GCM evaluation because (1) comparing band-by-band CRE avoids the compensating biases in the broadband CRE comparison and (2) the fractional contribution of each band to the LW broadband CRE (f(sub CRE)) is sensitive to cloud top height but largely insensitive to cloud fraction, presenting thus a diagnostic metric to separate the two macroscopic properties of clouds. Recent studies led by the first author have established methods to derive such band ]by ]band quantities from collocated AIRS and CERES observations. We present here a study that compares the observed band-by-band CRE over the tropical oceans with those simulated by three different atmospheric GCMs (GFDL AM2, NASA GEOS-5, and CCCma CanAM4) forced by observed SST. The models agree with observation on the annual ]mean LW broadband CRE over the tropical oceans within +/-1W/sq m. However, the differences among these three GCMs in some bands can be as large as or even larger than +/-1W/sq m. Observed seasonal cycles of f(sub CRE) in major bands are shown to be consistent with the seasonal cycle of cloud top pressure for both the amplitude and the phase. However, while the three simulated seasonal cycles of f(sub CRE) agree with observations on the phase, the amplitudes are underestimated. Simulated interannual anomalies from GFDL AM2 and CCCma CanAM4 are in phase with observed anomalies. The spatial distribution of f(sub CRE) highlights the discrepancies between models and observation over the low-cloud regions and the compensating biases from different bands

Preventing Ischial Pressure Ulcers: III. Clinical Pilot Study of Chronic Neuromuscular Electrical Stimulation

Objective: BIONs™ (BIOnic Neurons) are injectable, wireless microstimulators that make chronic BION Active Seating (BAS) possible for pressure ulcer prevention (PUP). Neuromuscular electrical stimulation (NMES) produces skeletal motion and activates trophic factors, counteracting three major etiological mechanisms leading to pressure ulcers (PUs): immobility, soft-tissue atrophy, and ischemia. Companion papers I and II reviewed prior experience with NMES for PUP, and analyzed the biomechanical considerations, respectively. This paper presents a treatment strategy derived from this analysis, and the clinical results of the first three cases

Randomized controlled trial of influenza vaccine in patients with heart failure to reduce adverse vascular events (IVVE): Rationale and design

Background: Influenza is associated with an increase in the risk of cardiac and other vascular events. Observational data and small randomized trials suggest that influenza vaccination may reduce such adverse vascular events. Research Design and Methods: In a randomized controlled trial patients with heart failure are randomized to receive either inactivated influenza vaccine or placebo annually for 3 years. Patients aged ≥18 years with a clinical diagnosis of heart failure and NYHA functional class II, III and IV are eligible. Five thousand patients from 10 countries where influenza vaccination is not common (Asia, the Middle East, and Africa) have been enrolled. The primary outcome is a composite of the following: cardiovascular death, non-fatal myocardial infarction, non-fatal stroke and hospitalizations for heart failure using standardized criteria. Analyses will be based on comparing event rates between influenza vaccine and control groups and will include time to event, rate comparisons using Poisson methods, and logistic regression. The analysis will be conducted by intention to treat i.e. patients will be analyzed in the group in which they were assigned. Multivariable secondary analyses to assess whether variables such as age, sex, seasonality modify the benefits of vaccination are also planned for the primary outcome. Conclusion: This is the largest randomized trial to test if influenza vaccine compared to control reduces adverse vascular events in high risk individuals

Mutational spectra of aflatoxin B

Aflatoxin B₁ (AFB₁) and/or hepatitis B and C viruses are risk factors for human hepatocellular carcinoma (HCC). Available evidence supports the interpretation that formation of AFB₁-DNA adducts in hepatocytes seeds a population of mutations, mainly G:C→T:A, and viral processes synergize to accelerate tumorigenesis, perhaps via inflammation. Responding to a need for early-onset evidence predicting disease development, highly accurate duplex sequencing was used to monitor acquisition of high-resolution mutational spectra (HRMS) during the process of hepatocarcinogenesis. Four-day-old male mice were treated with AFB₁ using a regimen that induced HCC within 72 wk. For analysis, livers were separated into tumor and adjacent cellular fractions. HRMS of cells surrounding the tumors revealed predominantly G:C→T:A mutations characteristic of AFB₁ exposure. Importantly, 25% of all mutations were G→T in one trinucleotide context (CGC; the underlined G is the position of the mutation), which is also a hotspot mutation in human liver tumors whose incidence correlates with AFB₁ exposure. The technology proved sufficiently sensitive that the same distinctive spectrum was detected as early as 10 wk after dosing, well before evidence of neoplasia. Additionally, analysis of tumor tissue revealed a more complex pattern than observed in surrounding hepatocytes; tumor HRMS were a composite of the 10-wk spectrum and a more heterogeneous set of mutations that emerged during tumor outgrowth. We propose that the 10-wk HRMS reflects a short-term mutational response to AFB₁, and, as such, is an early detection metric for AFB₁-induced liver cancer in this mouse model that will be a useful tool to reconstruct the molecular etiology of human hepatocarcinogenesis.National Institutes of Health (U.S.) (Grant R01-ES016313)National Institutes of Health (U.S.) (Grant P30-ES002109)National Institutes of Health (U.S.) (Grant T32-ES007020)National Institutes of Health (U.S.) (Grant R01-CA080024

Deep sequencing analysis of mutations resulting from the incorporation of dNTP analogs

Next-generation DNA sequencing technology was used to score >100 000 mutations resulting from exposure of a nucleic acid template to a mutagenic dNTP analog during a single pass of a DNA polymerase. An RNA template of known secondary structure was reverse transcribed in the presence of 8-oxo-dGTP, dPTP or both, followed by forward transcription in the presence of standard NTPs. Each mutagen, whether used alone or in combination, resulted in a highly characteristic mutation profile. Mutations were generated at a mean frequency of 1–2% per eligible nucleotide position, but there was substantial variation in the frequency of mutation at different positions, with a SD close to the mean. This variation was partly due to the identity of the immediately surrounding nucleotides and was not significantly influenced by the secondary structure of the RNA template. Most of the variation appears to result from idiosyncratic features that derive from local sequence context, demonstrating how different genetic sequences have different chemical phenotypes

The Scientific Investigation of Unidentified Aerial Phenomena (UAP) Using Multimodal Ground-based Observatories

Peer reviewedPublisher PD