Toward Next Generation Clinical Diagnostic Instruments: Scaling and New Processing Paradigms

Looking toward future clinical diagnostic instruments, there is little debate as to the features that need improvement over the current state-of-the-art. Increasing the speed and sensitivity of the assays, while reducing costs are clear goals. Recently, it has become possible to microminiaturize fluidic and sensing components using micromachining and precision injection molding. There has been a large amount of interest and effort in the area of miniaturization of such systems, yet not all of the properties of fluidics and sensing methods improve as they are drastically reduced in size. It is clear that implementing miniaturized diagnostic instruments is not a matter of simply shrinking their conventional counterparts, nor of automating existing manual procedures. What is required to harness the full potential of scaling technologies is the use of design methods that take into account scaling effects and the development of completely new processing approaches. Beginning with a general overview of the relevant scaling principles, sample preparation and detection approaches are addressed in this context.     

Laparoscopic treatment of liver tumours using a two-needle probe bipolar radiofrequency ablation device

BackgroundMany hepatobiliary centres are increasingly utilizing thermocoagulative devices such as bipolar-radiofrequency ablation (B-RFA). Compared with monopolar-radiofrequency ablation (M-RFA), B-RFA does not require grounding pads, thereby avoiding dermal burn injuries, and does not position probes directly into the tumour but rather on the perimeter. Additionally, B-RFA can precoagulate parenchyma to assist in hepatic resection. Herein, we report our early experience using B-RFA.MethodsA retrospective review identified 68 patients who underwent M-RFA or B-RFA between June 2004 and September 2010 in an academic centre. Peri-operative metrics were analysed.ResultsM-RFA was used to treat 30 patients, whereas B-RFA was used for 17 patients. There were no differences in peri-operative metrics, survival or disease recurrence between M-RFA and B-RFA. Seventeen additional patients underwent B-RFA precoagulation during laparoscopic resection (segmentectomy in eleven patients and multi-segmental resection in six patients). Four patients with multifocal disease underwent procedures that combined B-RFA with resection.ConclusionsThe early experience utilizing B-RFA demonstrates equivalency to M-RFA with respect to peri-operative metrics and survival. Moreover, B-RFA can be utilized to precoagulate tissue during a planned resection, making it not only a useful tool for tumour therapy but also a useful adjunct during surgical resections.     

Diabetes prediction,lipid accumulation product,and adiposity measures; 6-year follow-up: Tehran lipid and glucose study

Background

The body mass index (BMI) is the most commonly used marker for evaluating obesity related risks, however, central obesity measures have been proposed to be more informative. Lipid accumulation product (LAP) is an alternative continuous index of lipid accumulation, which is computed from waist circumference (WC, cm) and triglycerides (TGs, mmol/l): (WC-65) ×TG (men) and (WC-58) ×TG (women). We sought in this study to assess if LAP can outperform BMI, waist-to-height-ratio (WHtR), or waist-to-hip-ratio (WHpR) in identifying prevalent and predicting incident diabetes.

Results

The cross-sectional analyses were performed on a sample included 3,682 men and 4,989 women who were not pregnant, aged ≥ 20 years. According to the age (≥ 50 and <50 years) - and sex-specific analyses, odds ratios (ORs) of LAP for prevalent diabetes were higher than those of BMI, WHpR, or WHtR among women, after adjustment for mean arterial pressure and family history of diabetes. The OR of LAP in old men was lower than those of other adiposity measures; in young men, however, LAP was superior to BMI but identical to WHpR and WHtR in identifying prevalent diabetes. Except in young men, LAP showed highest area under the receiver operating characteristic curves (AROC) for prevalent diabetes (P for trend ≤ 0.005).For longitudinal analyses, a total of 5,018 non-diabetic subjects were followed for ~6 years. The ORs of BMI, WHpR, and WHtR were the same as those of LAP in both sexes and across age groups; except in young men where LAP was superior to the BMI. AROCs of LAP were relatively the same as anthropometric adiposity measures.

Conclusions

LAP was a strong predictor of diabetes and in young individuals had better predictability than did BMI; it was, however, similar to WHpR and WHtR in prediction of incident diabetes.

     

Vertical Mammaplasty Marking Using the Key Hole Pattern

Many modifications of the vertical mammaplasty procedure used to shorten the learning curve have been described. The authors advocate marking the breasts for the vertical mammaplasty operation according to the key hole pattern. They have used inverted T techniques on the upper breast and Lejour’s vertical mammaplasty on the lower breast. A total of 14 patients who had breast hypertrophy and ptosis underwent operations with this marking modification. The amount of removed breast ranged from 285 to 875 g per breast. Hematoma, skin necrosis, skin dehiscence, loss of nipple–areola sensitivity, and distortion were not observed in these cases.     

Heterogeneity in the smoking behavior of African American women

OBJECTIVE: To assess the association between sociodemographic variables and smoking behavior patterns of African American women. METHODS: Six years of data (N=14,903) from the National Health Interview Surveys were analyzed using multiple logistic regression. RESULTS: African American women in the South were more likely to never smoke and to start smoking later than women in the Northeast. Positive smoking outcomes (never smoking, initiating smoking at later ages, and quitting) were associated with higher education, higher income, and being married. CONCLUSIONS: Variations among African American women suggest the need for targeting specific subgroups at greater risks to reduce disparities in smoking and smoking-related diseases.     

Role of nitric oxide and prostaglandin systems in lithium modulation of acetylcholine vasodilation

The mechanism of lithium action, an effective treatment for bipolar disease, is still unknown. The present study examined the role of nitric oxide (NO) and prostaglandin systems in lithium modulation of acetylcholine in mesenteric vascular bed of rats by cannulating superior mesenteric artery. Acetylcholine (ACh) or sodium nitroprusside was injected under constant controlled flow induced by phenylephrine; therefore, changes in perfusion pressure reflect changes in resistance. Although 0.5 mM or 1 mM lithium-pretreatment of vascular bed causes reduction in ACh-response, 1.5 mM lithium induced no changes and 2 and 2.5 mM lithium potentiated ACh-induced mesenteric vascular bed relaxation compared to control group. Pretreatment of vascular bed with L-NAME or indomethacin decreased ACh-induced relaxation in 2 concentrations of 0.5 and 2 mM of lithium. The vasorelaxation response to sodium nitroprusside, the NO donor, was not different among lithium groups (0.5 and 2 mM) and controls. In conclusion, there is a dual modulation of endothelium-dependent relaxation, including an inhibitory effect at lower dose and a stimulating effect at higher dose of lithium in rat mesenteric vascular bed. NO synthesis or cyclooxygenase inhibition decreased vasorelaxation in both lower and higher doses of lithium, suggesting a role for NO and prostaglandin in this effect.     

Performance enhancement for audio-visual speaker identification using dynamic facial muscle model

Science of human identification using physiological characteristics or biometry has been of great concern in security systems. However, robust multimodal identification systems based on audio-visual information has not been thoroughly investigated yet. Therefore, the aim of this work to propose a model-based feature extraction method which employs physiological characteristics of facial muscles producing lip movements. This approach adopts the intrinsic properties of muscles such as viscosity, elasticity, and mass which are extracted from the dynamic lip model. These parameters are exclusively dependent on the neuro-muscular properties of speaker; consequently, imitation of valid speakers could be reduced to a large extent. These parameters are applied to a hidden Markov model (HMM) audio-visual identification system. In this work, a combination of audio and video features has been employed by adopting a multistream pseudo-synchronized HMM training method. Noise robust audio features such as Mel-frequency cepstral coefficients (MFCC), spectral subtraction (SS), and relative spectra perceptual linear prediction (J-RASTA-PLP) have been used to evaluate the performance of the multimodal system once efficient audio feature extraction methods have been utilized. The superior performance of the proposed system is demonstrated on a large multispeaker database of continuously spoken digits, along with a sentence that is phonetically rich. To evaluate the robustness of algorithms, some experiments were performed on genetically identical twins. Furthermore, changes in speaker voice were simulated with drug inhalation tests. In 3 dB signal to noise ratio (SNR), the dynamic muscle model improved the identification rate of the audio-visual system from 91 to 98%. Results on identical twins revealed that there was an apparent improvement on the performance for the dynamic muscle model-based system, in which the identification rate of the audio-visual system was enhanced from 87 to 96%.     

KP544, a nerve growth factor amplifier: Pharmacokinetics,safety, and efficacy in the rat

In cultured cells, KP544 [2‐amino‐5‐(4‐chlorophenylethynyl)‐4‐(4‐trans‐hydroxycyclohexyl amino) pyrimidine] amplifies differentiation initiated by nerve growth factor (NGF) or cAMP. This report describes the pharmacokinetics, safety, and neuroprotective efficacy of KP544 in rats. After an oral dose of 10 mg/kg KP544 was 25% bioavailable with a plasma half‐life of 1.3 h and brain levels 6‐fold higher than plasma levels at 4 and 8 h post‐dose. In a safety study, daily oral dosing for 30 days at 10 and 100 mg/kg was well tolerated. The favorable pharmacokinetic and safety profiles, together with its amplification of NGF in vitro, prompted evaluation of KP544 in two models involving NGF deficiencies. In the first model, brains were lesioned with intrastriatal injections of quinolinic acid. KP544 at oral doses of 0.02 to 1.0 mg/kg/day almost completely prevented the resulting learning deficits as evaluated using a radial‐arm‐water maze. At the lowest dose, there was a slower onset of functional improvement. These effects were accompanied by reductions (16–34%) in the striatal lesion size that were greatest at the highest dose and comparable to those seen with NGF therapy. The second model involved a peripheral neuropathy induced by taxol that is associated with decreases in NGF. KP544 at oral doses of 0.1–10 mg/kg/day decreased the severity of the neuropathy as measured by caudal nerve conduction velocities (30–70% return to control values). In both models, KP544 had a large therapeutic index suggesting its potential as a new approach for treating clinical disorders involving deficiencies in NGF. Drug Dev. Res. 62:60–70, 2004. © 2004 Wiley‐Liss, Inc.     

Smoking practices in New York City: The use of a population-based survey to guide policy-making and programming

To inform New York City’s (NYC’s) tobacco control program, we identified the neighborhoods with the highest smoking rates, estimated the burden of second-band smoke exposure, assessed the early response to state taxation, and examined cessation practices. We used a stratified random design to conduct a digit-dialed telephone survey in 2002 among 9,674 New York City adults. Our main outcome measures included prevalence of cigarette smoking, exposure to second-hand smoke, the response of smokers to state tax increases, and cessation practices. Even after controlling for sociodemographic factors (age, racelethnicity, income, education, marital status, employment status, and foreign-born status) smoking rates were highest in Central Harlem and in the South Bronx. Sixteen percent of nonsmokers reported frequent exposure to second-hand smoke at home or in a workplace. Among smokers with a child with asthma, only 33% reported having a no-smoking policy in their homes. More than one fifth of smokers reported reducing the number of cigarettes they smoked in response to the state tax increase. Of current smokers who tried to quit, 65% used no cessation aid. These data were used to inform New York City’s smoke-free legislation, taxation, public education, and a free nicotine patch give-away program. In conclusion, large, local surveys can provide essential data to effectively advocate for, plan, implement, and evaluate a comprehensive tobacco control program. Dr. Mostashari (the guarantor) made substantial contributions to the conception, design, and supervision of this paper, the analysis and interpretation of data, the drafting of the paper, critical revisions of the paper for important intellectual content, and the acquisition of data and funding for this research. Dr. Kerker made substantial contributions to the analysis and interpretation of data, the drafting of the paper and critical revisions of the paper for important intellectual content. Ms. Hajat made substantial contributions to the acquisition of data and critical revisions of the paper for important intellectual content. Dr. Miller made substantial contributions to the conception of this paper and critical revisions of the paper for important intellectual content. Dr. Frieden made substantial contributions to the conception, design, and supervision of this paper and critical revisions of the paper for important intellectual content.