SimPS-Net: Simultaneous Pose & Segmentation Network of Surgical Tools

Localisation of surgical tools during operation is of paramount importance in the context of robotic assisted surgery. 3D pose estimation can be utilised to explore the interaction of tools with registered tissue and improve the motion planning of robotic platforms, thus avoiding potential collisions with external agents. With the problems of traditional tracking systems being cost and the need to redesign surgical tools to accommodate markers, there has been a shift towards image-based, markerless tracking techniques. This study introduces a network capable of detecting and localising tools in 3D using a monocular setup. For training and validation, a novel dataset, 3dStool, was produced, and the network was trained to obtain a mean Dice coefficient of 85.0% for detection, along with a mean position and orientation error of 5.5mm and 3.3. respectively. The presented method is significantly more versatile than various state of the art solutions, as it requires no prior knowledge regarding the 3D structure of the tracked tools. The results were compared to standard pose estimation networks using the same dataset and demonstrated lower errors along most metrics. In addition, the generalisation capabilities of the proposed network were explored by performing inference on a previously unseen pair of scissors

Real-time active constraint generation and enforcement for surgical tools using 3D detection and localisation network

Introduction: Collaborative robots, designed to work alongside humans for manipulating end-effectors, greatly benefit from the implementation of active constraints. This process comprises the definition of a boundary, followed by the enforcement of some control algorithm when the robot tooltip interacts with the generated boundary. Contact with the constraint boundary is communicated to the human operator through various potential forms of feedback. In fields like surgical robotics, where patient safety is paramount, implementing active constraints can prevent the robot from interacting with portions of the patient anatomy that shouldn’t be operated on. Despite improvements in orthopaedic surgical robots, however, there exists a gap between bulky systems with haptic feedback capabilities and miniaturised systems that only allow for boundary control, where interaction with the active constraint boundary interrupts robot functions. Generally, active constraint generation relies on optical tracking systems and preoperative imaging techniques.Methods: This paper presents a refined version of the Signature Robot, a three degrees-of-freedom, hands-on collaborative system for orthopaedic surgery. Additionally, it presents a method for generating and enforcing active constraints “on-the-fly” using our previously introduced monocular, RGB, camera-based network, SimPS-Net. The network was deployed in real-time for the purpose of boundary definition. This boundary was subsequently used for constraint enforcement testing. The robot was utilised to test two different active constraints: a safe region and a restricted region.Results: The network success rate, defined as the ratio of correct over total object localisation results, was calculated to be 54.7% ± 5.2%. In the safe region case, haptic feedback resisted tooltip manipulation beyond the active constraint boundary, with a mean distance from the boundary of 2.70 mm ± 0.37 mm and a mean exit duration of 0.76 s ± 0.11 s. For the restricted-zone constraint, the operator was successfully prevented from penetrating the boundary in 100% of attempts.Discussion: This paper showcases the viability of the proposed robotic platform and presents promising results of a versatile constraint generation and enforcement pipeline.</jats:p

Mantle cell lymphoma of the gastrointestinal tract presenting with multiple intussusceptions – case report and review of literature

<p>Abstract</p> <p>Background</p> <p>Mantle cell lymphoma (MCL) is an aggressive type of B-cell non-Hodgkin's lymphoma that originates from small to medium sized lymphocytes located in the mantle zone of the lymph node. Extra nodal involvement is present in the majority of cases, with a peculiar tendency to invade the gastro-intestinal tract in the form of multiple lymphomatous polyposis. MCL can be accurately diagnosed with the use of the highly specific marker Cyclin D1. Few cases of mantle cell lymphoma presenting with intussuception have been reported. Here we present a rare case of multiple intussusceptions caused by mantle cell lymphoma and review the literature of this disease.</p> <p>Case presentation</p> <p>A 68-year-old male presented with pain, tenderness in the right lower abdomen, associated with nausea and non-bilious vomiting. CT scan of abdomen revealed ileo-colic intussusception. Laparoscopy confirmed multiple intussusceptions involving ileo-colic and ileo-ileal segments of gastrointestinal tract. A laparoscopically assisted right hemicolectomy and extended ileal resection was performed. Postoperative recovery was uneventful. The histology and immuno-histochemistry of the excised small and large bowel revealed mantle cell lymphoma with multiple lymphomatous polyposis and positivity to Cyclin D1 marker. The patient was successfully treated with Rituximab-CHOP chemotherapy and remains in complete remission at one-year follow-up.</p> <p>Conclusion</p> <p>This is a rare case of intestinal lymphomatous polyposis due to mantle cell lymphoma presenting with multiple small bowel intussusceptions. Our case highlights laparoscopic-assisted bowel resection as a potential and feasible option in the multi-disciplinary treatment of mantle cell lymphoma.</p

Protease-sensitive synthetic prions

Prions arise when the cellular prion protein (PrP(C)) undergoes a self-propagating conformational change; the resulting infectious conformer is designated PrP(Sc). Frequently, PrP(Sc) is protease-resistant but protease-sensitive (s) prions have been isolated in humans and other animals. We report here that protease-sensitive, synthetic prions were generated in vitro during polymerization of recombinant (rec) PrP into amyloid fibers. In 22 independent experiments, recPrP amyloid preparations, but not recPrP monomers or oligomers, transmitted disease to transgenic mice (n = 164), denoted Tg9949 mice, that overexpress N-terminally truncated PrP. Tg9949 control mice (n = 174) did not spontaneously generate prions although they were prone to late-onset spontaneous neurological dysfunction. When synthetic prion isolates from infected Tg9949 mice were serially transmitted in the same line of mice, they exhibited sPrP(Sc) and caused neurodegeneration. Interestingly, these protease-sensitive prions did not shorten the life span of Tg9949 mice despite causing extensive neurodegeneration. We inoculated three synthetic prion isolates into Tg4053 mice that overexpress full-length PrP; Tg4053 mice are not prone to developing spontaneous neurological dysfunction. The synthetic prion isolates caused disease in 600-750 days in Tg4053 mice, which exhibited sPrP(Sc). These novel synthetic prions demonstrate that conformational changes in wild-type PrP can produce mouse prions composed exclusively of sPrP(Sc)

Miller Early Childhood Sustained Home-visiting (MECSH) trial: design, method and sample description

<p>Abstract</p> <p>Background</p> <p>Home visiting programs comprising intensive and sustained visits by professionals (usually nurses) over the first two years of life show promise in promoting child health and family functioning, and ameliorating disadvantage. Australian evidence of the effectiveness of sustained nurse home visiting in early childhood is limited. This paper describes the method and cohort characteristics of the first Australian study of sustained home visiting commencing antenatally and continuing to child-age two years for at-risk mothers in a disadvantaged community (the Miller Early Childhood Sustained Home-visiting trial).</p> <p>Methods and design</p> <p>Mothers reporting risks for poorer parenting outcomes residing in an area of socioeconomic disadvantage were recruited between February 2003 and March 2005. Mothers randomised to the intervention group received a standardised program of nurse home visiting. Interviews and observations covering child, maternal, family and environmental issues were undertaken with mothers antenatally and at 1, 12 and 24 months postpartum. Standardised tests of child development and maternal-child interaction were undertaken at 18 and 30 months postpartum. Information from hospital and community heath records was also obtained.</p> <p>Discussion</p> <p>A total of 338 women were identified and invited to participate, and 208 were recruited to the study. Rates of active follow-up were 86% at 12 months, 74% at 24 months and 63% at 30 months postpartum. Participation in particular data points ranged from 66% at 1 month to 51% at 24 months postpartum. Rates of active follow-up and data point participation were not significantly different for the intervention or comparison group at any data point. Mothers who presented for antenatal care prior to 20 weeks pregnant, those with household income from full-time employment and those who reported being abused themselves as a child were more likely to be retained in the study. The Miller Early Childhood Sustained Home-visiting trial will provide Australian evidence of the effectiveness of sustained nurse home visiting for children at risk of poorer health and developmental outcomes.</p> <p>Trial registration</p> <p>ACTRN12608000473369</p

Analysis of SNPs and Haplotypes in Vitamin D Pathway Genes and Renal Cancer Risk

In the kidney vitamin D is converted to its active form. Since vitamin D exerts its activity through binding to the nuclear vitamin D receptor (VDR), most genetic studies have primarily focused on variation within this gene. Therefore, analysis of genetic variation in VDR and other vitamin D pathway genes may provide insight into the role of vitamin D in renal cell carcinoma (RCC) etiology. RCC cases (N = 777) and controls (N = 1,035) were genotyped to investigate the relationship between RCC risk and variation in eight target genes. Minimum-p-value permutation (Min-P) tests were used to identify genes associated with risk. A three single nucleotide polymorphism (SNP) sliding window was used to identify chromosomal regions with a False Discovery Rate of <10%, where subsequently, haplotype relative risks were computed in Haplostats. Min-P values showed that VDR (p-value = 0.02) and retinoid-X-receptor-alpha (RXRA) (p-value = 0.10) were associated with RCC risk. Within VDR, three haplotypes across two chromosomal regions of interest were identified. The first region, located within intron 2, contained two haplotypes that increased RCC risk by approximately 25%. The second region included a haplotype (rs2239179, rs12717991) across intron 4 that increased risk among participants with the TC (OR = 1.31, 95% CI = 1.09–1.57) haplotype compared to participants with the common haplotype, TT. Across RXRA, one haplotype located 3′ of the coding sequence (rs748964, rs3118523), increased RCC risk 35% among individuals with the variant haplotype compared to those with the most common haplotype. This study comprehensively evaluated genetic variation across eight vitamin D pathway genes in relation to RCC risk. We found increased risk associated with VDR and RXRA. Replication studies are warranted to confirm these findings

Local estrogen metabolism in epithelial ovarian cancer suggests novel targets for therapy

AbstractEpithelial ovarian cancer (EOC) accounts for about 90% of malignant ovarian tumors, and estrogen is often implicated in disease progression. We therefore compared the potential for gating of estrogen action via pre-receptor metabolism in normal human ovarian surface epithelium (OSE), EOC and selected EOC cell lines (SKOV3 and PEO1). Steroid sulphatase (STS), estrogen sulfotransferase (EST), 17β-hydroxysteroid dehydrogenases 2 (17BHSD2) and 5 (17BHSD5) mRNAs, proteins and enzymatic activities were all detectable in primary cell cultures of OSE and EOC, whereas aromatase and 17BHSD1 expression was negligible. qRT-PCR assay on total mRNA revealed significantly higher EST mRNA expression in OSE compared to EOC (P<0.05). Radioenzymatic measurements confirmed reduced sulfoconjugation (neutralization) of free estrogen in EOC relative to OSE. OSE cells were more effective at converting free [3H]-E1 to [3H]-E1S or [3H]-E2S, while EOC cell lines mainly converted [3H]-E1 to [3H]-E2 with minimal formation of [3H]-E1S or [3H]-E2S. IL1α treatment suppressed EST (P<0.01) and 17BHSD2 (P<0.001) mRNA levels in OSE and stimulated STS mRNA levels (P<0.001) in cancer (SKOV3) cells. These results show that estrogen is differentially metabolized in OSE and EOC cells, with E2 ‘activation’ from conjugated estrogen predominating in EOC. Inflammatory cytokines may further augment the local production of E2 by stimulating STS and suppressing EST. We conclude that local estrogen metabolism may be a target for EOC treatment

Significant benefits of AIP testing and clinical screening in familial isolated and young-onset pituitary tumors

Context Germline mutations in the aryl hydrocarbon receptor-interacting protein (AIP) gene are responsible for a subset of familial isolated pituitary adenoma (FIPA) cases and sporadic pituitary neuroendocrine tumors (PitNETs). Objective To compare prospectively diagnosed AIP mutation-positive (AIPmut) PitNET patients with clinically presenting patients and to compare the clinical characteristics of AIPmut and AIPneg PitNET patients. Design 12-year prospective, observational study. Participants & Setting We studied probands and family members of FIPA kindreds and sporadic patients with disease onset ≤18 years or macroadenomas with onset ≤30 years (n = 1477). This was a collaborative study conducted at referral centers for pituitary diseases. Interventions & Outcome AIP testing and clinical screening for pituitary disease. Comparison of characteristics of prospectively diagnosed (n = 22) vs clinically presenting AIPmut PitNET patients (n = 145), and AIPmut (n = 167) vs AIPneg PitNET patients (n = 1310). Results Prospectively diagnosed AIPmut PitNET patients had smaller lesions with less suprasellar extension or cavernous sinus invasion and required fewer treatments with fewer operations and no radiotherapy compared with clinically presenting cases; there were fewer cases with active disease and hypopituitarism at last follow-up. When comparing AIPmut and AIPneg cases, AIPmut patients were more often males, younger, more often had GH excess, pituitary apoplexy, suprasellar extension, and more patients required multimodal therapy, including radiotherapy. AIPmut patients (n = 136) with GH excess were taller than AIPneg counterparts (n = 650). Conclusions Prospectively diagnosed AIPmut patients show better outcomes than clinically presenting cases, demonstrating the benefits of genetic and clinical screening. AIP-related pituitary disease has a wide spectrum ranging from aggressively growing lesions to stable or indolent disease course