Precise and low-power closed-loop neuromodulation through algorithm-integrated circuit co-design.

Implantable neuromodulation devices have significantly advanced treatments for neurological disorders such as Parkinson's disease, epilepsy, and depression. Traditional open-loop devices like deep brain stimulation (DBS) and spinal cord stimulators (SCS) often lead to overstimulation and lack adaptive precision, raising safety and side-effect concerns. Next-generation closed-loop systems offer real-time monitoring and on-device diagnostics for responsive stimulation, presenting a significant advancement for treating a range of brain diseases. However, the high false alarm rates of current closed-loop technologies limit their efficacy and increase energy consumption due to unnecessary stimulations. In this study, we introduce an artificial intelligence-integrated circuit co-design that targets these issues and using an online demonstration system for closed-loop seizure prediction to showcase its effectiveness. Firstly, two neural network models are obtained with neural-network search and quantization strategies. A binary neural network is optimized for minimal computation with high sensitivity and a convolutional neural network with a false alarm rate as low as 0.1/h for false alarm rejection. Then, a dedicated low-power processor is fabricated in 55 nm technology to implement the two models. With reconfigurable design and event-driven processing feature the resulting application-specific integrated circuit (ASIC) occupies only 5mm2 silicon area and the average power consumption is 142 µW. The proposed solution achieves a significant reduction in both false alarm rates and power consumption when benchmarked against state-of-the-art counterparts.

Minimally Invasive Hypoglossal Nerve Stimulator Enabled by ECG Sensor and WPT to Manage Obstructive Sleep Apnea.

A hypoglossal nerve stimulator (HGNS) is an invasive device that is used to treat obstructive sleep apnea (OSA) through electrical stimulation. The conventional implantable HGNS device consists of a stimuli generator, a breathing sensor, and electrodes connected to the hypoglossal nerve via leads. However, this implant is bulky and causes significant trauma. In this paper, we propose a minimally invasive HGNS based on an electrocardiogram (ECG) sensor and wireless power transfer (WPT), consisting of a wearable breathing monitor and an implantable stimulator. The breathing external monitor utilizes an ECG sensor to identify abnormal breathing patterns associated with OSA with 88.68% accuracy, achieved through the utilization of a convolutional neural network (CNN) algorithm. With a skin thickness of 5 mm and a receiving coil diameter of 9 mm, the power conversion efficiency was measured as 31.8%. The implantable device, on the other hand, is composed of a front-end CMOS power management module (PMM), a binary-phase-shift-keying (BPSK)-based data demodulator, and a bipolar biphasic current stimuli generator. The PMM, with a silicon area of 0.06 mm2 (excluding PADs), demonstrated a power conversion efficiency of 77.5% when operating at a receiving frequency of 2 MHz. Furthermore, it offers three-voltage options (1.2 V, 1.8 V, and 3.1 V). Within the data receiver component, a low-power BPSK demodulator was ingeniously incorporated, consuming only 42 µW when supplied with a voltage of 0.7 V. The performance was achieved through the implementation of the self-biased phase-locked-loop (PLL) technique. The stimuli generator delivers biphasic constant currents, providing a 5 bit programmable range spanning from 0 to 2.4 mA. The functionality of the proposed ECG- and WPT-based HGNS was validated, representing a highly promising solution for the effective management of OSA, all while minimizing the trauma and space requirements.

H-CNN: Spatial Hashing Based CNN for 3D Shape Analysis.

We present a novel spatial hashing based data structure to facilitate 3D shape analysis using convolutional neural networks (CNNs). Our method builds hierarchical hash tables for an input model under different resolutions that leverage the sparse occupancy of 3D shape boundary. Based on this data structure, we design two efficient GPU algorithms namely hash2col and col2hash so that the CNN operations like convolution and pooling can be efficiently parallelized. The perfect spatial hashing is employed as our spatial hashing scheme, which is not only free of hash collision but also nearly minimal so that our data structure is almost of the same size as the raw input. Compared with existing 3D CNN methods, our data structure significantly reduces the memory footprint during the CNN training. As the input geometry features are more compactly packed, CNN operations also run faster with our data structure. The experiment shows that, under the same network structure, our method yields comparable or better benchmark results compared with the state-of-the-art while it has only one-third memory consumption when under high resolutions (i.e., 2563).

Seroprevalence of pertussis in China: need to improve vaccination strategies.

Pertussis remains an important cause of infant death worldwide and is an ongoing public health concern even in countries with high vaccination coverage. A cross-sectional seroepidemiological study was undertaken to estimate true incidence rates and gain further insight into the epidemiology and burden of pertussis in China. During 2011, a total of 1080 blood samples were obtained from healthy individuals between 0 and 86 y of age in Zhengzhou, Central China. Serum IgG antibodies against pertussis toxin (PT) and filamentous hemagglutinin (FHA) were measured quantitatively using ELISA. The results showed that the geometric mean titers of PT and FHA IgG were 6.48 IU/mL (95% CI: 5.70-7.41 IU/mL) and 11.39 IU/mL (95% CI: 10.22-12.87 IU/mL) among subjects less than 4 y of age, indicating that pertussis antibody levels were low despite high vaccination coverage. Of the 850 subjects≥4 y of age, 56 (6.6%) had anti-PT IgG titers above 30 IU/mL, and 11 (1.3%) had antibodies titers above 80 IU/mL. The estimated age-specific incidence of infection with B. pertussis revealed a peak incidence in the 31 to 40 y age group, followed by the 41 to 60 y age group. Taken together, these results indicate that pertussis is common in Chinese subjects in Zhengzhou, especially in adults, suggesting that the disease burden is underestimated in China. Therefore, our study stresses the importance of strengthening the diagnostic capacity and improving surveillance system for delineating current epidemiological profiles of pertussis. Most importantly, it may be advisable to re-evaluate the current Chinese pertussis immunization schedule and implement to booster doses for older children, adolescents and adults.

Cone Tracing for Furry Object Rendering.

We present a cone-based ray tracing algorithm for high-quality rendering of furry objects with reflection, refraction and defocus effects. By aggregating many sampling rays in a pixel as a single cone, we significantly reduce the high supersampling rate required by the thin geometry of fur fibers. To reduce the cost of intersecting fur fibers with cones, we construct a bounding volume hierarchy for the fiber geometry to find the fibers potentially intersecting with cones, and use a set of connected ribbons to approximate the projections of these fibers on the image plane. The computational cost of compositing and filtering transparent samples within each cone is effectively reduced by approximating away in-cone variations of shading, opacity and occlusion. The result is a highly efficient ray tracing algorithm for furry objects which is able to render images of quality comparable to those generated by alternative methods, while significantly reducing the rendering time. We demonstrate the rendering quality and performance of our algorithm using several examples and a user study.

[Immunogenicity and safety of DTaP-IPV//PRP-T combined vaccine in infants in China].

OBJECTIVE: The aim of this study was to demonstrate the immunogenicity and safety of diphtheria, tetanus, pertussis (acellular, component), poliomyelitis (inactivated) vaccine (adsorbed) and Haemophilus influenzae type b conjugate vaccine (DTaP-IPV//PRP-T) combined vaccine compared with commercially available DTaP (diphtheria, tetanus and pertussis), Haemophilus influenzae type b (Hib), tetanus conjugate and IPV monovalent vaccine. METHODS: Subjects were randomly divided into three groups, Group A and Group B were DTaP-IPV//PRP-T combined vaccine (PENTAXIM(TM)) vaccinated at 2, 3, 4 months of age or 3, 4, 5 months of age respectively; Group C was commercially available DTaP. Hib tetanus conjugate (Act-HIB(TM)) and IPV (IMOVAX PolioTM(TM)) vaccines vaccinated at 3, 4, 5 months of age. All groups received booster dose at 18 to 20 months of age, with antibody titers tested. Non-inferiority analysis was demonstrated in terms of seroprotection/seroconversion rates between Group A, Group B respectively and Group C. Safety information was collected after each vaccination to assess the safety of investigational vaccines. RESULTS: The non-inferiority of DTaP-IPV//PRP-T combined vaccine vaccinated at 2, 3, 4 or 3, 4, 5 months of age versus DTaP, Hib tetanus conjugate and IPV vaccine was demonstrated for all vaccine antigens in both primary and booster phases in terms of seroprotection/seroconversion rates. DTaP-IPV//PRP-T combined vaccine was well tolerated. The rate of solicited/unsolicited severe adverse reactions was very low and similar to the control vaccines. CONCLUSION: DTaP-IPV//PRP-T combined vaccine was highly immunogenic with good safety profile in Chinese infants, which was comparable to the commercially available control vaccines.

Radiance transfer biclustering for real-time all-frequency biscale rendering.

We present a real-time algorithm to render all-frequency radiance transfer at both macroscale and mesoscale. At a mesoscale, the shading is computed on a per-pixel basis by integrating the product of the local incident radiance and a bidirectional texture function. While at a macroscale, the precomputed transfer matrix, which transfers the global incident radiance to the local incident radiance at each vertex, is losslessly compressed by a novel biclustering technique. The biclustering is directly applied on the radiance transfer represented in a pixel basis, on which the BTF is naturally defined. It exploits the coherence in the transfer matrix and a property of matrix element values to reduce both storage and runtime computation cost. Our new algorithm renders at real-time frame rates realistic materials and shadows under all-frequency direct environment lighting. Comparisons show that our algorithm is able to generate images that compare favorably with reference ray tracing results, and has obvious advantages over alternative methods in storage and preprocessing time.

Effect of vaccination on Bordetella pertussis strains, China.

Whole-cell pertussis vaccine was introduced in China in the early 1960s. We used standard typing methods to compare 96 Bordetella pertussis isolates collected before and after introduction of vaccination, during 1953-2005. The following vaccine-type alleles of the pertussis toxin (ptx) gene were characteristic for all prevaccination strains: ptxA2, ptxA3, and ptxA4. The shift to ptxA1 occurred since 1963. All isolates collected since 1983 contained ptxA1. Pertactin (prn) allele 1, prn1, was predominant, although prn2 and prn3 have been detected since 2000. Serotypes fimbriae (Fim) 2 and Fim2,3 were found in all isolates collected before 1986. During 1997-2005, Fim3 became prevalent. Although changes in electrophoresis profiles over time were observed, the predominant profiles during 1997-2005 resembled those during the prevaccine era and those found in Europe before the 1990s. B. pertussis strains in China may differ from those in countries that have a long history of high vaccine coverage.

Triplex real-time PCR assay for detection and differentiation of Bordetella pertussis and Bordetella parapertussis.

A triplex real-time PCR assay for detection and differentiation of Bordetella pertussis and Bordetella parapertussis was developed. Three targets were used for amplification in a single tube: the insertion sequence IS481 and the pertussis toxin promoter region (ptxP) for B. pertussis, and the insertion sequence IS1001 for B. parapertussis. The performance of this PCR assay was evaluated in parallel in three single-target real-time PCR assays using DNA extracted from B. pertussis and B. parapertussis reference strains and nasopharyngeal swabs taken from 105 patients who had been coughing for more than 7 days. The minimum detection limit of the triplex PCR was one to five colony-forming units (CFU) of B. pertussis and 1 CFU of B. parapertussis per reaction, and the coefficients of both intra- and inter-assay variation were less than 7%. Results were available within 4 h. Of the 105 nasopharyngeal samples, seven were culture positive and 23 were PCR positive for B. pertussis. All culture-positive samples were also PCR positive. Our single-tube triplex real-time PCR assay proved to be sensitive, specific and suitable for simultaneous detection and discrimination of B. pertussis and B. parapertussis.

Safety and immunogenicity of a diphtheria, tetanus, acellular pertussis and Haemophilus influenzae Type b combination vaccine compared with separate administration of licensed equivalent vaccines in Chinese infants and toddlers for primary and booster immunization.

To evaluate the safety and immunogenicity of a diphtheria, tetanus, acellular pertussis and Haemophilus infuenzae Type b (DTaP/Hib) combination vaccine first developed by a Chinese manufacturer, a randomized, two-stage, parallel controlled, single center clinical trial was conducted in Dafeng, Jiangsu Province of China. A total of 720 infants were enrolled and randomly assigned to two groups with a 2:1 allocation. In Stage I, 480 subjects in Group T were administered with 3 doses of the DTaP/Hib vaccine at 3, 4 and 5 months of age, respectively, while 240 subjects in Group C received separate licensed DTaP vaccine and Hib conjugate vaccine on the same schedule. In Stage II, 633 primed toddlers (431 of Group T and 202 of Group C) were given a booster dose at 18 months of age. Sera samples were collected at pre-dose 1, 4 weeks post-dose 3, pre-dose 4 and 4 weeks post-dose 4, respectively. Levels of protective antibodies were measured by Enzyme Linked Immunoadsorbent Assay (ELISA). Immunogenicity was evaluated with regard to geometric mean concentrations (GMCs), seroconversion rates and seroprotection rates of the antibodies. Solicited adverse reactions were recorded for 3 days after each dose; unsolicited adverse events and serious adverse events were monitored for 28 days after vaccination. Results showed that seroconversion rates of anti-pertussis toxoid (PT), anti-filamentous hemagglutinin (FHA), anti-diphtheria toxoid (DT), anti-tetanus toxid (TT) and anti-polyribosyl-ribitol-phosphate (PRP) in Group T (Stage I: 98.06%, 97.33%, 100%, 100%, 98.79%; Stage II: 99.18%, 83.42%, 99.18%, 63.32%, 85.05%) were comparable to that of Group C (Stage I: 95.26%, 93.16%, 100%, 100%, 98.42%; Stage II: 98.89%, 83.89%, 98.33%, 53.89%, 76.67%). Nearly 100% of the subjects in both groups achieved seroprotective levels of anti-DT (> or = 0.1IU/ml), anti-TT (> or = 0.1IU/ml) and anti-PRP (> or = 0.15 microg/ml) after primary and booster vaccination. The frequencies of local induration, swelling and redness as well as general reactions such as fever, diarrhea and anaphylaxis were low and acceptable in both groups. In conclusion, the DTaP/Hib vaccine was demonstrated to be non-inferior to the control vaccines on safety and immunogenicity. There could be a bright future for the DTaP/Hib vaccine to be widely used in the universal vaccination of Chinese children.

Booster vaccination against pertussis in Chinese children at six years of age using reduced antigen content diphtheria-tetanus-acellular pertussis vaccine (Boostrix()).

Pertussis continues to circulate in Chinese communities and older children, adolescents and adults are sources of infection for unprotected infants. Two studies conducted in Jiangsu Province in the People's Republic of China assessed the immunogenicity, reactogenicity and safety of Boostrix(), a combined reduced antigen content diphtheria-tetanus-acellular pertussis vaccine (dTpa) when administered as a booster dose to children 6 to 8 years of age. Immunogenicity was assessed before and one month after vaccination in a subset. Reactogenicity was assessed over a 4-day follow-up using diary cards. A total of 690 Chinese subjects were enrolled. Boostrix() was well tolerated. One month after the booster dose, 100% of dTpa recipients had seroprotective antibody concentrations against diphtheria and tetanus. The percentage of subjects with a response against pertussis antigens (using locally defined cut-offs) was 91.9% for pertussis toxoid, 98.8% for filamentous hemagglutinin, and 100% for pertactin. The exploratory analysis showed no statistically significant differences between dTpa or diphtheria-tetanus vaccine in terms of the percentage of subjects with seroprotective antibodies against diphtheria or tetanus. These studies demonstrate that Boostrix() is well tolerated and immunogenic when administered as a booster dose to 6 to 8 year old Chinese children previously immunized with a combined diphtheria-tetanus-pertussis vaccine. Introduction of dTpa into the routine Chinese immunization schedule would provide booster vaccination against pertussis without the addition of further injections into the Chinese vaccination schedule and is likely to promote improved pertussis control in older children.

Production and characterization of recombinant pertactin, fimbriae 2 and fimbriae 3 from Bordetella pertussis.

BACKGROUND: Bordetella pertussis is a causative agent of pertussis or whooping cough in humans. Pertactin (Prn), fimbriae 2 (Fim2) and fimbriae 3 (Fim3) of B. pertussis are important virulence factors and immunogens which have been included in some acellular pertussis vaccines. In this present study, we cloned, expressed and purified Prn, Fim2 and Fim3, respectively. The immunogenicity and protective efficacy of the three recombinant proteins (rPrn, rFim2 and rFim3) were investigated in mouse model. RESULTS: Three recombinant proteins with amount of 12 to 25 mg/L were produced. Compared to the control mice only immunized with adjuvant, serum IgG antibody responses were significantly induced in the mice immunized with rPrn, rFim2 or rFim3 (P < 0.001 for all three proteins). Furthermore, T cell responses characteristic of increased production of IL-2 and TNF-alpha (only for rPrn) were elicited in the mice immunized with the three proteins (P < 0.05 for all three proteins). Immunization with rPrn, but not with rFim2 or rFim3, significantly enhanced clearance of bacteria in the lungs of mice after intranasal challenge with B. pertussis (P < 0.05). When tested in a lethal intracerebral infection model, certain protection was observed in mice immunized with rPrn. CONCLUSIONS: We have developed an efficient method to produce large amounts of rPrn, rFim2, and rFim3 from B. pertussis. The three recombinant proteins induced both humoral and cellular immune responses in mice. Immunization with rPrn also conferred protection against pertussis in mouse infection models. Our results indicated that the recombinant proteins still retain their immunological properties and highlighted the potential of the recombinant proteins for the future development of the B. pertussis vaccines.

Protective immunity against Bordetella pertussis by a recombinant DNA vaccine and the effect of coinjection with a granulocyte-macrophage colony stimulating factor gene.

A recombinant pertussis DNA vaccine was described here with its immunogenicity and the ability to induce protection against B. pertussis infection in mice. Three immunodominant antigen gene fragments of pertussis, pertussis toxin subunit 1 (pts1), fragments of pertactin (prn) and filamentous hemagglutinin (fha), were recombined as fragment pts1-prn-fha named ppf, and it was cloned to plasmid pVAX1 as pVAX1/ppf. Compared to those injected with pVAX1, the mice injected with pVAX1/ppf significantly elicited more antigen specific antibody anti-PTS1, anti-PRN, anti-FHA and cytokine IL-10, IFN-gamma. When pGM-CSF was coinjected with pVAX1/ppf, the mice showed significantly increases of the three antibodies and cytokine IL-10, IL-4, IFN-gamma and TNF-alpha compared to those injected with pVAX1 only. The mice in group pVAX1/ppf & pGM-CSF, in particular; induced much more anti-PTS1, IL-4 and TNF-alpha than those in group pVAX1/ppf. In the intracerebral mouse protection test, the mice immunized with pVAX1/ppf or pVAX1/ppf & pGM-CSF induced protection to a lethal dose of B. pertussis. The results indicate that recombinant DNA vaccine and pGM-CSF coinjection can induce protective immunity against B. pertussis, demonstrating a valuable method to prevent pertussis.