Mechanical Characterization of Synthetic Mesh for Pelvic Organ Prolapse Repair

Pelvic organ prolapse (POP) is characterized by the abnormal descent of the pelvic organs into the vaginal canal. POP is associated with urinary, defacatory, and sexual dysfunction, in addition to psychological disorders including depression. Prolapse is quite common, with ~50% of women over the age of 50 exhibiting some degree of prolapse, and over 200,000 surgical repairs in the United States annually. During surgical repair, a graft is used to restore support to the vagina, re-approximating the normal anatomy. Given the high failure rate of native tissue repair, use of polypropylene mesh has become widespread. Despite the prevalence of synthetic mesh, complication rates are ~20%, with little known about its behavior following implantation. Therefore, this dissertation aims to rigorously characterize the mechanical behavior of synthetic mesh, with the goal of optimizing device design for use in the pelvic floor. First, micro- and macro-level deformation of mesh was assessed in response to mechanical loads using uniaxial testing and 3D reconstruction. Upon loading, mesh pores significantly deformed, yielding textile dimensions that are known to heighten the foreign body response. In addition, point loads significantly wrinkled the mesh surface, further reducing mesh dimensions and producing configurations consistent with those found clinically. Next, a finite element model for synthetic mesh was developed, using a novel method to allow for textile properties to be measured in-silico. This model was validated using a custom testing apparatus to simultaneously load and image transvaginal mesh products. Evaluation of mesh deformation found experimental and computational results to be similar, demonstrating the predictive capabilities of this model. The validated model was then used to examine the sensitivity of mesh behavior to variable loading conditions. Here the magnitude and orientation of tensile forces were found to significantly predict undesired deformations. Finally, computational mesh models were combined with MRI reconstructions of patient specific anatomy to simulate the development of prolapse and mesh repair. Again, mesh pores experienced significant deformation upon anatomical fixation, corresponding with clinical sites of exposure and pain. In total, this dissertation provides a tool for the evaluation and optimization of synthetic mesh devices prior to implantation and pre-surgical evaluation of mesh procedures

Academic neurosurgery in the UK: present and future directions.

Academic neurosurgery encompasses basic science and clinical research efforts to better understand and treat diseases of relevance to neurosurgical practice, with the overall aim of improving treatment and outcome for patients. In this article, we provide an overview of the current and future directions of British academic neurosurgery. Training pathways are considered together with personal accounts of experiences of structured integrated clinical academic training and unstructured academic training. Life as an academic consultant is also described. Funding is explored, for the specialty as a whole and at the individual level. UK academic neurosurgical organisations are highlighted. Finally, the UK's international standing is considered

Relationship of age, gender, race, and body size to infrarenal aortic diameter

AbstractPurpose: To assess the effects of age, gender, race, and body size on infrarenal aortic diameter (IAD) and to determine expected values for IAD on the basis of these factors.Methods: Veterans aged 50 to 79 years at 15 Department of Veterans Affairs medical centers were invited to undergo ultrasound measurement of IAD and complete a prescreening questionnaire. We report here on 69,905 subjects who had no previous history of abdominal aortic aneurysm (AAA) and no ultrasound evidence of AAA (defined as IAD ≥ 3.0 cm).Results: Although age, gender, black race, height, weight, body mass index, and body surface area were associated with IAD by multivariate linear regression (all p < 0.001), the effects were small. Female sex was associated with a 0.14 cm reduction in IAD and black race with a 0.01 cm increase in IAD. A 0.1 cm change in IAD was associated with large changes in the independent variables: 29 years in age, 19 cm or 40 cm in height, 35 kg in weight, 11 kg/m2 in body mass index, and 0.35 m2 in body surface area. Nearly all height-weight groups were within 0.1 cm of the gender means, and the unadjusted gender means differed by only 0.23 cm. The variation among medical centers had more influence on IAD than did the combination of age, gender, race, and body size.Conclusions: Age, gender, race, and body size have statistically significant but small effects on IAD. Use of these parameters to define AAA may not offer sufficient advantage over simpler definitions (such as an IAD ≥3.0 cm) to be warranted. (J Vasc Surg 1997;26:595-601.

Mutations in the Gene DNAJC5 Cause Autosomal Dominant Kufs Disease in a Proportion of Cases: Study of the Parry Family and 8 Other Families

Background: The Neuronal Ceroid Lipofuscinoses (NCL) comprise at least nine progressive neurodegenerative genetic disorders. Kufs disease, an adult-onset form of NCL may be recessively or dominantly inherited. Our study aimed to identify genetic mutations associated with autosomal dominant Kufs disease (ADKD). Methodology and Principal Findings We have studied the family first reported with this phenotype in the 1970s, the Parry family. The proband had progressive psychiatric manifestations, seizures and cognitive decline starting in her mid 20s. Similarly affected relatives were observed in seven generations. Several of the affected individuals had post-mortem neuropathological brain study confirmatory for NCL disease. We conducted whole exome sequencing of three affected family members and identified a pLeu116del mutation in the gene DNAJC5, which segregated with the disease phenotype. An additional eight unrelated affected individuals with documented autosomal dominant or sporadic inheritance were studied. All had diagnostic confirmation with neuropathological studies of brain tissue. Among them we identified an additional individual with a p.Leu115Arg mutation in DNAJC5. In addition, a pAsn477Ser change in the neighboring gene PRPF6, a gene previously found to be associated with retinitis pigmentosa, segregated with the ADKD phenotype. Interestingly, two individuals of the Parry family did report visual impairment. Conclusions: Our study confirmed the recently reported association of DNAJC5 mutations with ADKD in two out of nine well-defined families. Sequence changes in PRPF6 have not been identified in other unrelated cases. The association of vision impairment with the expected PRPF6 dysfunction remains possible but would need further clinical studies in order to confirm the co-segregation of the visual impairment with this sequence change

The impact of diabetes mellitus on survival following resection and adjuvant chemotherapy for pancreatic cancer

BACKGROUND: Diabetes mellitus is frequently observed in pancreatic cancer patients and is both a risk factor and an early manifestation of the disease. METHODS: We analysed the prognostic impact of diabetes on the outcome of pancreatic cancer following resection and adjuvant chemotherapy using individual patient data from three European Study Group for Pancreatic Cancer randomised controlled trials. Analyses were carried out to assess the association between clinical characteristics and the presence of preoperative diabetes, as well as the effect of diabetic status on overall survival. RESULTS: In total, 1105 patients were included in the analysis, of whom 257 (23%) had confirmed diabetes and 848 (77%) did not. Median (95% confidence interval (CI)) unadjusted overall survival in non-diabetic patients was 22.3 (20.8–24.1) months compared with 18.8 (16.9–22.1) months for diabetic patients (P=0.24). Diabetic patients were older, had increased weight and more co-morbidities. Following adjustment, multivariable analysis demonstrated that diabetic patients had an increased risk of death (hazard ratio: 1.19 (95% CI 1.01, 1.40), P=0.034). Maximum tumour size of diabetic patients was larger at randomisation (33.6 vs 29.7 mm, P=0.026). CONCLUSIONS: Diabetes mellitus was associated with increased tumour size and reduced survival following pancreatic cancer resection and adjuvant chemotherapy

DTT - Divertor Tokamak Test facility: A testbed for DEMO

The effective treatment of the heat and power exhaust is a critical issue in the road map to the realization of the fusion energy. In order to provide possible, reliable, well assessed and on-time answers to DEMO, the Divertor Tokamak Test facility (DTT) has been conceived and projected to be carried out and operated within the European strategy in fusion technology. This paper, based on the invited plenary talk at the 31st virtual SOFT Conference 2020, provides an overview of the DTT scientific proposal, which is deeply illustrated in the 2019 DTT Interim Design Report

Quantifying neutralising antibody responses against SARS-CoV-2 in dried blood spots (DBS) and paired sera

The ongoing SARS-CoV-2 pandemic was initially managed by non-pharmaceutical interventions such as diagnostic testing, isolation of positive cases, physical distancing and lockdowns. The advent of vaccines has provided crucial protection against SARS-CoV-2. Neutralising antibody (nAb) responses are a key correlate of protection, and therefore measuring nAb responses is essential for monitoring vaccine efficacy. Fingerstick dried blood spots (DBS) are ideal for use in large-scale sero-surveillance because they are inexpensive, offer the option of self-collection and can be transported and stored at ambient temperatures. Such advantages also make DBS appealing to use in resource-limited settings and in potential future pandemics. In this study, nAb responses in sera, venous blood and fingerstick blood stored on filter paper were measured. Samples were collected from SARS-CoV-2 acutely infected individuals, SARS-CoV-2 convalescent individuals and SARS-CoV-2 vaccinated individuals. Good agreement was observed between the nAb responses measured in eluted DBS and paired sera. Stability of nAb responses was also observed in sera stored on filter paper at room temperature for 28 days. Overall, this study provides support for the use of filter paper as a viable sample collection method to study nAb responses.</p

Search of the Orion spur for continuous gravitational waves using a loosely coherent algorithm on data from LIGO interferometers

We report results of a wideband search for periodic gravitational waves from isolated neutron stars within the Orion spur towards both the inner and outer regions of our Galaxy. As gravitational waves interact very weakly with matter, the search is unimpeded by dust and concentrations of stars. One search disk (A) is 6.87° in diameter and centered on 20h10m54.71s+33°33′25.29′′, and the other (B) is 7.45° in diameter and centered on 8h35m20.61s-46°49′25.151′′. We explored the frequency range of 50-1500 Hz and frequency derivative from 0 to -5×10-9 Hz/s. A multistage, loosely coherent search program allowed probing more deeply than before in these two regions, while increasing coherence length with every stage. Rigorous follow-up parameters have winnowed the initial coincidence set to only 70 candidates, to be examined manually. None of those 70 candidates proved to be consistent with an isolated gravitational-wave emitter, and 95% confidence level upper limits were placed on continuous-wave strain amplitudes. Near 169 Hz we achieve our lowest 95% C.L. upper limit on the worst-case linearly polarized strain amplitude h0 of 6.3×10-25, while at the high end of our frequency range we achieve a worst-case upper limit of 3.4×10-24 for all polarizations and sky locations. © 2016 American Physical Society

CMS physics technical design report : Addendum on high density QCD with heavy ions

Peer reviewe

DTT - Divertor Tokamak Test facility - Interim Design Report

The “Divertor Tokamak Test facility, DTT” is a milestone along the international program aimed at demonstrating – in the second half of this century – the feasibility of obtaining to commercial electricity from controlled thermonuclear fusion. DTT is a Tokamak conceived and designed in Italy with a broad international vision. The construction will be carried out in the ENEA Frascati site, mainly supported by national funds, complemented by EUROfusion and European incentive schemes for innovative investments. The project team includes more than 180 high-standard researchers from ENEA, CREATE, CNR, INFN, RFX and various universities. The volume, entitled DTT Interim Design Report (“Green Book” from the colour of the cover), briefly describes the status of the project, the planning of the design future activities and its organizational structure. The publication of the Green Book also provides an occasion for thorough discussions in the fusion community and a broad international collaboration on the DTT challenge