DST Group Research Articles

A Retrospective Study Distinguishing between Hyperacusis and Misophonia in children with Auditory Processing Disorder (APD)

ObjectivesDecreased sound tolerance (DST) is common in children with auditory processing disorder (APD). This study aimed to differentiate between hyperacusis and misophonia in children with APD. DesignA retrospective study evaluating outcomes of structured history and co-morbidity following Research Domain Criteria (RDoC) frame-work. Misophonia was considered as oversensitivity to eating/chewing sounds and hyperacusis as oversensitivity to other sounds. Study sampleTwo hundred and seventy-nine children (160 males; 119 females), 6-16 year-olds with NVIQ ≥80, diagnosed with APD between January 2021 and December 2022. ResultsOne hundred and forty-three out of 279 children with APD had DST, of which 107 had hyperacusis (without misophonia) and 36 had misophonia. Misophonia co-existed with hyperacusis in 35 children (97 %), and in one child misophonia occurred without hyperacusis. Misophonia was prevalent in older children, in females, and those with tinnitus. Fear and being upset were predominant emotional responses in hyperacusis (without misophonia) while disgust and verbal abuse were prevalent in misophonia (with or without hyperacusis). Compared to children without DST, the hyperacusis (without misophonia) and misophonia (with or without hyperacusis) groups had significant higher prevalence of ADHD, anxiety, and language impairment. Educational difficulties were similar in APD irrespective of the presence or absence of DST. Despite higher tinnitus prevalence in misophonia (with or without hyperacusis) along with similar co-morbidities and educational difficulties in both hyperacusis (without misophonia) and misophonia (with or without hyperacusis), the misophonia (with or without hyperacusis) group surprisingly had less support at school which was reflected in fewer Education, Health and Care Plan (EHCP). ConclusionsIn APD misophonia mostly co-exists with hyperacusis, with differences in emotional responses, tinnitus prevalence, and gender distribution when compared to hyperacusis (without misophonia). Increase in awareness about misophonia is needed, as children with misophonia may have unidentified needs. Larger scale prospective study is required to clarify if misophonia evolves from hyperacusis, and to explore the factors underlying ‘misophonia with hyperacusis’ and ‘misophonia without hyperacusis’. For clarity, DST studies need to specify if hyperacusis or misophonia co-existed when referring to hyperacusis or misophonia.

QMAC-DST for Rapid Detection of Drug Resistance in Pulmonary Tuberculosis Patients: A Multicenter Pre-Post Comparative Study.

Background/Objectives: This study explores the impact of QMAC-DST, a rapid, fully automated phenotypic drug susceptibility test (pDST), on the treatment of tuberculosis (TB) patients. Methods: This pre-post comparative study, respectively, included pulmonary TB patients who began TB treatment between 1 December 2020 and 31 October 2021 (pre-period; pDST using the Löwenstein-Jensen (LJ) DST (M-kit DST)) and between 1 November 2021 and 30 September 2022 (post-period; pDST using the QMAC-DST) in five university-affiliated tertiary care hospitals in South Korea. We compared the turnaround times (TATs) of pDSTs and the time to appropriate treatment for patients whose anti-TB drugs were changed based on these tests between the groups. All patients were permitted to use molecular DSTs (mDSTs). Results: A total of 182 patients (135 in the M-kit DST group and 47 in the QMAC-DST group) were included. The median TAT was 36 days for M-kit DST (interquartile range (IQR), 30-39) and 12 days for QMAC-DST (IQR, 9-15), with the latter being significantly shorter (p < 0.001). Of the total patients, 10 (5.5%) changed their anti-TB drugs based on the mDST or pDST results after initiating TB treatment (8 in the M-kit DST group and 2 in the QMAC-DST group). In the M-kit DST group, three (37.5%) patients changed anti-TB drugs based on the pDST results. In the QMAC-DST group, all changes were due to mDST results; therefore, calculating the time to appropriate treatment for patients whose anti-TB drugs were changed based on pDST results was not feasible. In the QMAC-DST group, 46.8% of patients underwent the first-line line probe assay compared to 100.0% in the M-kit DST group (p < 0.001), indicating that rapid QMAC-DST results provide quicker assurance of the ongoing treatment by confirming susceptibility to the current anti-TB drugs. Conclusions: QMAC-DST delivers pDST results more rapidly than LJ-DST, ensuring faster confirmation for the current treatment regimen.

Phenotypic and genomic comparison of dominant and nondominant sequence-type of Acinetobacter baumannii isolated in China.

A. baumannii is a common clinical pathogen that often causes pneumonia and bloodstream infections in ICU patients. Sequence types (ST) are used to investigate the distribution and spread of A. baumannii. Biological characteristics such as virulence and resistance may play a role in A. baumannii becoming a specific dominant ST(DST,ST191, ST195 and ST208) strain. To characterize the biological, genetic, and transcriptomic differences between the DST and non-dominant ST(NST,ST462 and ST547,etc.) strains in A. baumannii, we performed several biological experiments and genetic, and transcriptomic analyses. The DST group displayed more resistance ability to desiccation, oxidation, multiple antibiotics, and complement killing than the NST group. However, the latter had higher biofilm formation ability than the former. The genomic analysis showed the DST group exhibited more capsule-related and aminoglycoside-resistant genes. Besides, GO analysis indicated that functions involved in lipid biosynthetic, transport, and the metabolic process were up-regulated in the DST group, while KEGG analysis manifested that the two-component system related to potassium ion transport and pili were down-regulated. In short, resistance to desiccation, oxidation, multiple antibiotics, and serum complement killing are important reasons for the formation of DST. Genes related to capsule synthesis and lipid biosynthesis and metabolism play an important role at the molecular level in the formation of DST.

Comparison between the double‐syringe and the single‐syringe techniques of adenosine administration for terminating supraventricular tachycardia: A pilot, randomized controlled trial

BackgroundAdenosine has been recommended as a first‐line treatment for stable supraventricular tachycardia (SVT). Standard guidelines recommend 6‐mg of adenosine administered intravenously (IV) with an immediate 20‐ml IV bolus of normal saline solution (NSS; double syringe technique [DST]). However, a newly proposed single‐syringe technique (SST), in which adenosine is diluted with an up to 20 ml IV bolus of NSS, was found to be beneficial.HypothesisWe hypothesized that the SST was noninferior to the DST for terminating stable SVT.MethodsA pilot multicenter, single‐blind, randomized controlled study was conducted at nine hospitals in north and northeast Thailand. Thirty patients who were diagnosed with stable SVT were randomized into two groups of 15, with one receiving adenosine via the DST and the other via the SST. We examined SVT termination, the average successful dose, and the complication rate of each group. Analyses were based on the intention‐to‐treat principle.ResultThe termination rate was 93.3% in the DST and 100% in the SST group (p = 1.000), and the success rate of the first 6‐mg dose of adenosine was 73.3% and 80%, respectively (p = 1.000). The total administered dose was 8.6 ± 5.1 mg in the DST group and 7.6 ± 4.5 mg in the SST group (p = .608). No complications were found in either group.ConclusionsThe SST was non‐inferior to the DST for termination of SVT. However, a further definitive study with a larger sample size is required.

Abstract 10470: Comparison Between the Double-Syringe Technique and the Single-Syringe Diluted with Normal Saline Technique of Adenosine for a Termination of Supraventricular Tachycardia: A Pilot, Randomized, Single-Blind Controlled Trial (Do-Single Trial)

Introduction: Supraventricular tachycardia (SVT) is a condition commonly found in emergency settings. Adenosine is recommended as the first-line treatment for stable patients, however, it is rapidly metabolized. The ACLS guidelines recommend administration of 6-mg adenosine intravenously (IV) with an immediate 20-ml normal saline solution (NSS) IV (double syringe technique; DST). However, adenosine diluted with NSS up to 20 ml IV (single syringe technique; SST) was as well found effective for terminating the arrhythmia. Hypothesis: The SST is non-inferior to the DST for terminating stable SVT. Methods: A pilot, single-blind, randomized, controlled study was conducted from January to December 2020 at 4 hospitals in the northeastern region, Thailand. Thirty patients who presented with stable regular narrow complex tachycardia, diagnosed as stable SVT by cardiologists, were enrolled. They were randomized into the DST and SST groups, 15 patients each. We evaluated the termination of SVT (turned to normal sinus rhythm), the average successful doses, and the complication rate of each group. Analyses were based on the intention to treat principle. Results: The termination rate was 91.7% and 83.3% in the DST and the SST group, P =0.990. The success rate of 6-mg adenosine was 75% and 66.7% in the DST and the SST group, P =0.640. The total administration dose was 8.2±4.9 mg in the DST group, and 10.0±5.9 mg in the SST group, P =0.432. There was no difference in the complication rate between both groups. Conclusions: Adenosine diluted with NSS up to 20 ml administered IV was non-inferior to the conventional technique for terminating SVT. A further definitive study with larger sample size is required.

Value of amplitude-integrated electroencephalogram combined with quantitative indices of cranial magnetic resonance imaging in predicting short-term neurodevelopment in moderately and late preterm infants: a prospective study.

To study the association of amplitude-integrated electroencephalogram (aEEG) and the quantitative indices biparietal width (BPW) and interhemispheric distance (IHD) of cranial magnetic resonance imaging (cMRI) with short-term neurodevelopment in moderately and late preterm infants. A total of 104 moderately and late preterm infants who were admitted to the neonatal intensive care unit from September 2018 to April 2020 were selected as the subjects for this prospective study. The Naqeeb method and sleep-wake cycling (SWC) were used for aEEG assessment within 72 hours after birth. cMRI was performed at the corrected gestational age of 37 weeks. BPW and IHD were measured at the T2 coronal position. At the corrected age of 6 months, the Developmental Screening Test for Child Under Six (DST) was used to follow up neurodevelopment. According to developmental quotient (DQ), the infants were divided into a normal DST group (78 infants with DQ≥85) and an abnormal DST group (26 infants with DQ<85). Related indices were compared between the two groups. The association between aEEG and cMRI was evaluated. Compared with the normal DST group, the abnormal DST group had significantly lower aEEG normal rate and SWC maturation rate (P<0.05), as well as a significantly larger IHD and a significantly smaller BPW (P<0.05). Immature SWC, aEEG abnormality, and a relatively large IHD were the risk factors for abnormal DST (P<0.05), and a relatively large BPW was a protective factor against abnormal DST (P<0.05). For moderately and late preterm infants, aEEG within 72 hours after birth and the quantitative indices BPW and IHD of cMRI at the corrected gestational age of 37 weeks may affect their neurodevelopmental outcome at the corrected age of 6 months.

Applying digital storytelling in the medical oncology curriculum: Effects on students’ achievement and critical thinking

BackgroundDigital storytelling (DST), which combines traditional storytelling with digital tools, can provide a narrative pedagogy that promotes critical thinking (CT). However, we found no previous study in medical education. Materials and methodsThe aim of the study was to investigate if DST can promote CT and, if so, which CT skills were improved. Thirty-two students participated in a non-equivalent control group pretest-posttest research study, with 16 in each group. The participants were fifth-year medical students on a hematology rotation. We compared the routine instructional method (control group) with DST (intervention group). The measures of CT used for the pre- and post-test in both groups was the Health Science Reasoning Test (HRST) and knowledge test. We also evaluated the satisfaction of the students in DST group. We used Paired and independent t-tests for comparing the mean scores. To eliminate the confounding effect of pre-test on the results of the intervention, the ANCOVA test was used. ResultsThere was no significant difference in the overall CT pretest scores (P-value = 0.51) between the control and intervention groupsbut the difference was significant for the post-test scores (P-value = 0.03). Although post-test scores showed a significant increase (P-value = 0.002) compared to pre-test scores in the intervention group, no significant increase was observed in the control group (P-value = 0.26). Most students considered that DST improved their CT, deep learning, communication skills and team-working. ConclusionsThe study demonstrated that DST promoted CT. We recommend the use of DST to promote CT in clinical education placements.

Comparison of the short-term outcomes of using DST and PPH staplers in the treatment of grade III and IV hemorrhoids

Stapled hemorrhoidopexy has a few advantages such as less postoperative pain and faster recovery compared with conventional hemorrhoidectomy. There are two major devices used for stapled hemorrhoidopexy, PPH stapler (Ethicon EndoSurgery) and DST stapler (Covidien). This study was conducted to investigate the postoperative outcomes among patients with grade III and IV hemorrhoids who underwent hemorrhoidopexy with either of these two devices. A total of 242 consecutive patients underwent stapled hemorrhoidopexy with either PPH stapler (110 patients) or DST stapler (132 patients) at a single center in 2017. We performed a retrospective case–control study to compare the short-term postoperative outcomes and the complications between these two groups. After matching the cases in terms of age, gender, and the grade of hemorrhoids, there were 100 patients in each group (PPH versus DST). There were no significant differences in the postoperative visual analog scale (VAS) score and analgesic usage. Among complications, the incidence of anorectal stricture was significantly higher in the DST group (p = 0.02). Evaluation of the mucosal specimen showed that the total surface area, the muscle/mucosa ratio and the surface area of the muscle were also significantly higher in the DST group (p = 0.03). Further analysis of the DST group demonstrated that patients with anorectal stricture after surgery are younger than patients without anorectal stricture, and higher muscle/mucosa ratio (p = 0.03) and a higher surface area of the muscle (p = 0.03) also measured in the surgical specimen. The two devices provide similar outcomes of postoperative recovery. Patients who underwent DST stapled hemorrhoidopexy had a higher incidence rate of stricture, larger area of muscle excision, and higher muscle/mucosa ratio in the surgical specimen. Further investigation is warranted for a better understanding of the correlation between muscle excision and anorectal stricture.

Gait changes following direct versus contralateral strength training: A randomized controlled pilot study in individuals with multiple sclerosis

BackgroundContralateral strength training (CST) is increasingly investigated and employed as a non-conventional way to induce an indirect gain in strength in the weakened untrained limb. However, its effects on gait performance are more controversial. Research questionTo assess and compare the effects of contralateral (CST) and direct (DST) strength training on spatio-temporal parameters, kinematic and kinetic descriptors of gait in persons with relapsing-remitting multiple sclerosis (PwMS). MethodsTwenty-eight PwMS (EDSS 2.0–5.5) with inter-side difference in ankle dorsiflexors’ strength ≥ 20 % and moderate gait impairment (walking speed 0.70-0.94 m/s), were randomly assigned to a CST (undergoing training of the less-affected dorsiflexors) or DST group (where the most-affected dorsiflexors were trained). Before and after a 6-week high-intensity resistance training (three 25-minute sessions/week), PwMS underwent bilateral measurements of dorsiflexors’ maximal strength and assessment of gait spatio-temporal parameters, lower limb joint kinematics and kinetics. Results and significanceFollowing the training period, muscle strength increased significantly in both groups (on average, CST + 29.5 %, p < 0.0005; DST + 15.7 %, p = 0.001) with no difference between the two interventions. Significant changes in gait speed (+16.5 %; p < 0.0001) and stride length (+6.0 %; p = 0.04) were detected only after DST, while no difference was detected in the CST group. Ankle moment and ROM were unaffected by the training. In PwMS with mild to moderate disability and lower limb dorsiflexors’ strength asymmetry, CST was not inferior to DST in inducing significant strength gains in the untrained most-affected limb. However, only DST significantly improved gait performance and, specifically, walking speed. Even though CST did not worsen asymmetry, data suggest that contralateral approaches should not be recommended straightaway if the training goal is to improve outcomes other than strength and, specifically, walking speed.

Alteration in the mRNA expression of genes associated with gastrointestinal permeability and ileal TNF-\u03b1 secretion due to the exposure of silver nanoparticles in Sprague\u2013Dawley rats

BackgroundSilver ions from silver nanoparticles (AgNP) or AgNPs themselves itself that are ingested from consumer health care products or indirectly from absorbed food contact material can interact with the gastrointestinal tract (GIT). The permeability of the GIT is strictly regulated to maintain barrier function and proper nutrient absorption. The single layer intestinal epithelium adheres and communicates actively to neighboring cells and the extracellular matrix through different cell junctions. In the current study, we hypothesized that oral exposure to AgNPs may alter the intestinal permeability and expression of genes controlling cell junctions. Changes in cell junction gene expression in the ileum of male and female rats administered different sizes of AgNP for 13-weeks were assessed using qPCR.ResultsThe results of this study indicate that AgNPs have an altering effect on cell junctions that are known to dictate intestinal permeability. mRNA expression of genes representing tight junction (Cldn1, Cldn5, Cldn6, Cldn10 and Pecam1), focal adhesion (Cav1, Cav2, and Itgb2), adherens junction (Pvrl1, Notch1, and Notch2), and hemidesmosome (Dst) groups were upregulated significantly in females treated with 10 nm AgNP, while no change or downregulation of same genes was detected in male animals. In addition, a higher concentration of pro-inflammatory cytokine, TNF-α, was noticed in AgNP-treated female animals as compared to controls.ConclusionsThis study proposes that interaction of silver with GIT could potentially initiate an inflammatory process that could lead to changes in the gastrointestinal permeability and/or nutrient deficiencies in sex-specific manner. Fully understanding the mechanistic consequences of oral AgNP exposure may lead to stricter regulation for the commercial usage of AgNPs and/or improved clinical therapy in the future.

News &amp; information: Distinguished lectures in Queensland

The Queensland Chapter of the Aerospace and Electronic Systems Society was pleased to host two Distinguished Lectures in August and September, from Dr Joe Fabrizio, Acting Research Leader, Surveillance and Reconnaissance Systems at DST Group, and AES Society President; and Dr Eli Brookner, who retired in 2014 as a Principal Research Engineer after a 50-year career with Raytheon.

A Robust Feature Extraction and Parameterized Fitting Algorithm for Bottom‐Side Oblique and Vertical Incidence Ionograms

AbstractAutomatic processing of ionograms to extract ionospheric propagation characteristics and electron density profile parameters is an important enabling step toward constructing real time data‐assimilative models of the ionosphere. A robust and reliable feature extraction and fitting algorithm that supports both oblique and vertical incidence ionograms has recently been developed to enhance the regional ionospheric model for Australia's Jindalee Operational Radar Network. The so‐called DST‐IIP algorithm is an autoscaling technique based on a constrained quasi‐parabolic segment profile, which is modified from its climatological estimate to fit a set of key peak, edge, and line features in the ionogram image, representing the E, sporadic‐E (Es), and F2 layers. The F2 fitting, in particular, is performed in the ionogram domain, using analytic ray‐tracing and homing to produce a synthetic trace that reproduces the image features. Following thorough testing on a large database of midlatitude Australian ionograms, the DST‐IIP algorithm now runs routinely on‐board DST Group's Digital Oblique Receiving System. This paper provides an overview of the technique, along with sample results and performance statistics.

Gaussian mixture multitarget–multisensor Bernoulli tracker for multistatic sonobuoy fields

Sonobuoy fields, consisting of a large network of emitter and receiver sonar sensors on buoys, are increasingly being used for detection and tracking of underwater targets in a defined maritime area. This study presents a Gaussian mixture version of a multitarget-multisensor (MS) Bayesian-type tracker developed specifically for multistatic sonobuoy fields. Its foundation is the optimal Bayesian MS filter for a single target in clutter. The multi target feature is incorporated using the linear-multitarget paradigm, which is a fast and accurate approximation assuming the density of underwater targets is low. Reliable track initiation and false track discrimination for low signal-to-noise ratio targets are achieved using the amplitude feature of reported detections. The developed tracker is capable of processing measurements with different modalities, depending on the transmitted signal waveform. It is integrated and tested within a realistic multistatic sonar emulator developed by DST Group.

A UAS Testbed for the Flight Demonstration of Structural Health Monitoring Systems

The transition of airframe diagnostic technologies onto manned air vehicles is a complex process, with a timeline based on technological push, operator requirements and trust. The timeline includes stages for system development, validation, certification and implementation. The application of airframe diagnostic technologies on unmanned air vehicles offers a simpler route, which can expedite the development and validation cycles, and demonstrate the efficacy of the technologies hence building operator trust. With these benefits in mind, DST Group is developing an airframe sensor testbed upon which various airframe diagnostic systems (such as those used for structural health monitoring including optical fibre and acousto-ultrasonic based approaches) can be tested and have their usefulness verified. For initial demonstrations the testbed, based on a commercial-off-the-shelf hexacopter, was flown tethered in a laboratory setting. This paper presents results of the initial flight demonstration focusing on optical fibre measurements, in particular strain measurements with draw-tower fibre Bragg gratings.

The Acousto Ultrasonic Structural Health Monitoring Array Module (AUSAM+) for Damage Detection in Structures

An area of considerable interest within the aerospace community is the use of structurally-integrated transducers for detecting and monitoring damage in aircraft structures. Such Structural Health Monitoring (SHM) systems offer the possibility to provide non-destructive inspections on-demand and consequently provide a basis for condition-based maintenance on airframes. This approach potentially offers maintenance cost savings and possible improvements in performance when compared to current time-based techniques for detecting and monitoring structural damage. A wide-area damage detection technique under extensive investigation by researchers, on small-scale coupons to full-scale test articles, is acousto-ultrasonics (AU) using structurally-integrated piezoelectric transducers. For any SHM technique to be successfully applied to an operational aircraft in the field the SHM hardware needs to be fit for purpose i.e. easy to use, compact, portable, light, electrically and mechanically robust and provide reliable and accurate measurements. Additionally, in order for researchers to extend, demonstrate and validate AU based SHM techniques under various aerospace structural scenarios, instrumentation is required that is functionally flexible, expandable and relatively inexpensive. In order to facilitate the development, validation and implementation of AU based SHM in the aerospace community the Australian Defence Science and Technology Group (DST Group) has developed a compact device for AU excitation and interrogation, called the Acousto Ultrasonic Structural health monitoring Array Module (AUSAM+). The module, which has the footprint of a typical current generation smart phone, provides autonomous control of four send and receive piezoelectric elements, which can operate in pitch-catch or pulse-echo modes and can undertake electro-mechanical impedance measurements for transducer and structural diagnostics. Other key features include an ability to (1) accommodate larger transducer arrays by operating synchronously with other units, via an optical link; (2) cater for fibre optic sensing of acoustic waves with four intensity-based optical inputs; (3) measure temperature and strain; (4) be triggered externally; and (5) allow the users to easily access the full hardware functionality via a Matlab or Python hardware object, thus providing enormous flexibility for the creation of custom interfaces. This paper provides an overview of the system and its capabilities and demonstrates the efficacy of the system via a simple laboratory AU study on a flat plate.

Ageing of Australian DNAN Based Melt‐Cast Insensitive Explosives

Abstract2,4‐Dinitroanisole (DNAN) is a new melt‐cast matrix ingredient that replaces traditional TNT in TNT‐based melt‐cast explosives. Aside from sensitiveness improvements, the use of DNAN allows for the continued operation of existing melt‐cast facilities (for example the Australian Munitions plants located at Mulwala and Benalla) without the need for major plant modifications. Researchers at Defence Science and Technology Group (DST Group) have developed several DNAN based formulations that have been extensively characterized. In an effort to better understand the ageing properties of these formulations, an accelerated ageing program was undertaken. Testing was conducted under two different ageing conditions; the first test condition was conducted at a constant 60 °C with ambient humidity and the second test condition was the A2 diurnal cycle (representative of hot dry climates). Analysis of the formulation density, sensitiveness, mechanical and thermal properties was made at three‐month intervals for a period of 12 months and results compared with conventional explosives similarly aged. For all DNAN‐based formulations there was negligible change in impact, friction, electrostatic discharge, and thermal testing over time. These results highlight the ability of the ARX formulations to diurnal temperature cycling and to hold favorable sensitiveness properties to various stimuli.

Assessment of Methods for Rapid Intraoperative Concentration and Selection of Marrow-Derived Connective Tissue Progenitors for Bone Regeneration Using the Canine Femoral Multidefect Model

Treatment of large bone defects remains an unsolved clinical challenge, despite a wide array of existing bone graft materials and strategies. Local deficiency in osteogenic connective tissue progenitors (CTP-Os) due to tissue loss is one of the central biological barriers to bone regeneration. Density separation (DS) and selective retention (SR) represent two promising methods that can be used intraoperatively to rapidly concentrate cells and potentially select CTP-Os. This project was designed to compare DS and SR using the canine femoral multidefect (CFMD) model. Mineralized cancellous allograft (MCA) was used as a standardized scaffold for cell transplantation. Two experiments were performed using a cohort of six animals in each comparison. In Cohort I, unprocessed bone marrow aspirate (BMA) clot was compared to DS processing. MCA combined with raw BMA or DS processed cells produced a robust and advanced stage of bone regeneration throughout the defect in 4 weeks with reconstitution of hematopoietic marrow. However, the retention of DS processed cells and CTP-Os in the MCA matrix was low compared to BMA clot. In Cohort II, MCA with DS-T cells (addition of calcium chloride thrombin to induce clotting and enhance cell and CTP-O retention) was compared to MCA with SR cells. A mean of 276 ± 86 million nucleated cells and 29,030 ± 10,510 CTP-Os were implanted per defect in the DS-T group. A mean of 76 ± 42 million nucleated cells and 30,266 ± 15,850 CTP-Os were implanted in the SR group. Bone formation was robust and not different between treatments. Histologically, both groups demonstrated regeneration of hematopoietic marrow tissue. However, SR sites contained more hematopoietic vascular tissues, less fibrosis, and less residual allograft, particularly in the intramedullary cavity, suggesting a more advanced stage of remodeling (p = 0.04). These data demonstrate excellent overall performance of DS and SR processing methods. Both methods achieve a bone regeneration response that approaches the limits of performance that can be achieved in the CFMD model. Further advancement and comparison of these intraoperative bone marrow cell processing methods will require use of a larger and more biologically compromised defect site to guide the next steps of preclinical development and optimization.

Long-Term Functional Outcomes of Total Mesorectal Excision Following Chemoradiotherapy for Lower Rectal Cancer: Stapled Anastomosis versus Intersphincteric Resection

Aims: To compare the long-term functional outcomes of total mesorectal excision following chemoradiotherapy for lower rectal cancer between stapled anastomosis and intersphincteric resection (ISR). Methods: A total of 105 of 170 sphincter-preserving patients found to be disease-free and anal functional patients were assessed at 6.5 years (range 2.4-13.0 years) of follow-up after surgery. Of these subjects, 87 (double stapling technique [DST]: 41; ISR: 46) of the 105 patients (82.9%) responded to the questionnaire on the low anterior resection syndrome score (LARS score). Results: The total LARS scores in the DST and ISR groups were not significantly different (Major/Minor/No LARS = 23/14/4 and 31/10/5, p = 0.431). When considering each item of the LARS, ISR was associated with poorer incontinence scores than DST. Conversely, the scores for the frequency of bowel movement, clustering and urgency were not different between the 2 groups. In addition, in the multivariate analysis, the tumor distance from the anal verge and postoperative period was independently associated with Major LARS. Conclusion: In this study, we demonstrate the long-term functional outcomes of irradiated lower rectal cancer reconstructed with DST and ISR. Bowel function improves over time; therefore, long-term patient follow-up is important.

Differential Effect of Pretransplant Blood Transfusions on Immune Effector and Regulatory Compartments in HLA-Sensitized and Nonsensitized Recipients

Blood transfusion (BT) may elicit both harmful and beneficial immune responses against a subsequent organ graft. Immune parameters of a single, non leukocyte-depleted BT were investigated in two groups: non-human leukocyte antigen (HLA)-sensitized recipients with a one-HLA-DR matched donor (protocolled BT [PBT]) and females with previous exposure to HLA alloantigens through pregnancy (donor-specific transfusion [DST]). Thirty-five percent of DST recipients and 9.5% of PBT recipients developed HLA antibodies after BT.Phenotypic and functional analyses were performed in pre-BT, 2 weeks post-BT, and more than 10 weeks post-BT samples (PBT: n=10; DST: n=14). The number of donor-reactive interferon-γ-producing memory T cells increased 2 weeks post-BT, but only in the DST group, increased frequencies persisted beyond 10 weeks (P0.004). In the DST recipients, the proportion of natural killer cells (CD3(-)CD56(+)) significantly increased after BT (P=0.01), whereas in PBT recipients, the proportion of regulatoryT cells (CD4(+)CD25(+)Foxp3(+)CD127 low) significantly increased at 2 weeks post-BT (P=0.039). Microarray analysis confirmed increased activity of genes involved in function of natural killer cells,Tcells, and Bcells in DSTrecipients and increased expression of immune regulatory genes (galectin-1, Foxo3a, and follistatin-like 3) in PBT recipients. Galectin-1 expression by quantitative polymerase chain reaction was significantly enhanced in peripheral blood cells after PBT (P0.05). Decreased immune effector mechanisms combined with an increased immune regulatory cell signature after HLA-DR-matched BT in nonsensitized patients is in line with clinical observations of improved outcome of a subsequent graft. Previous sensitization, however, may lead to HLA antibody formation and prolonged donor-specific memory T-cell reactivity after BT.

Induction of rat cardiac allograft tolerance by combined blockade of OX40/OX40L and CD28/B7 and donor specific spleen cell transfusion

Objective To induce the tolerance to cardiac allograft by combined blockade of OX40/OX40L and CD28/B7 co-stimulatory signaling and donor specific spleen cell transfusion in rat mod-els of pre-existent allogenic reactive memory T lymphocytes. Methods Lewis rats that underwent 3 days of adoptive transfer of donor specific CD8~+ memory T cells, separated by immunomagnetic bead separation kit, received either separate or combined transfusion of AdCTLA4Ig, AdOX40Ig, donor spleen cells (DST) and transplantations of hearts of DA rats at the same time. Cardiac allografts were taken out 48 h after transplantation for histological analysis and cytokines expression ,and survival time of cardiac allografts with different treatments was observed. Results Compared with AdCTLA4Ig, AdOX40Ig and DST groups, AdCTLA4Ig + AdOX4OIg + DST group showed lower cardiac pathological grade with much lower expression level of IL-2 and IFN-γ,and much longer heart survival time. Conclusion Combined blockade of OX40/ OX40L and CD28/B7 and donor specific spleen cell transfusion could induce rat cardiac graft tolerance. Key words: Heart transplantation; Memory T lymphocytes; Immune tolerance