Surgery for pelvic organ prolapse: the quest to reduce failure rates

Female pelvic organ prolapse (FPOP) is a debilitating condition. In Australia, 19% of women require prolapse surgery in their lifetime and recurrence rates range as high as 40 – 60% in the anterior compartment. Given the high surgical failure rate, this thesis aimed to identify the use of mesh to improve surgical outcomes utilising translabial ultrasound as the principal study method. In a retrospective analysis of mesh use in vaginal repair, anterior mesh proved to have a lower recurrence rate compared to native tissue repair, and anterior anchored mesh such as the PerigeeTM was of maximum benefit only in women who had a levator avulsion, a risk factor for prolapse recurrence. Apical anchoring supports were also evaluated in this thesis. Vaginally, the anterior ElevateTM was found to be inferior compared to the PerigeeTM, highlighting the possible poorer load-bearing capability of the self-fixating anterior ElevateTM anchors, whilst abdominally, there was still a very high rate of cystocele recurrence (>80%) despite excellent apical support in those that had laparoscopic sacrocolpopexy. Regardless of anchoring methods, mesh repair did not seem to completely compensate for the effect of levator avulsion and it did not confer additional benefit in women with an enlarged levator hiatal area, another risk factor for prolapse recurrence. The Puborectalis sling was designed to prevent excessive levator hiatal enlargement and proof of concept was achieved in a phase II observational pilot study of 110 women. There was a mean reduction of the levator hiatal area by 12cm2 sustained for over two years. During the course of this work, the rise in reported mesh related complications had also led to heated debates over its use in urogynaecology. Prolapse repair with mesh shifted from being readily embraced to complete withdrawal of use in many countries. This work hopes to contribute to the evolving mesh literature and to outline an alternative operative approach in women at high risk of prolapse recurrence

Comments on "Design and performance evaluation of load distribution strategies for multiple loads on heterogeneous linear daisy chain networks''

Min, Veeravalli, and Barlas proposed strategies to minimize the overall execution time of one or several divisible loads on a heterogeneous linear network, using one or more installments. We show on a very simple example that the proposed approach does not always produce a solution and that, when it does, the solution is often suboptimal. We also show how to find an optimal scheduling for any instance, once the number of installments per load is given. Finally, we formally prove that under a linear cost model, as in the original paper, an optimal schedule has an infinite number of installments. Such a cost model can therefore not be sed to design practical multi-installment strategies

EFFECTS OF RENT-SEEKING ON ECONOMIC GROWTH IN LOW-INCOME ECONOMIES

Sluggish growth in low-income countries, despite the high performance in other economic indicators, motivates the literature to switch attention to institutions. Despite its crucial economic implications, there is limited attention on rent-seeking as a driver of economic growth in low-income countries. This paper investigates the effect of rent-seeking on growth in low-income countries from 2004 to 2017using the system generalized method of moments estimator. The empirical results reveal that rent-seeking negatively affects growth, implying that it obstructs the pace of economic development in low-income countries. Hence, it is necessary for policymakers in these countries to adopt anti-rent-seeking policies to promote a rapid and sustainable growth.Sluggish growth in low-income countries, despite the high performance in other economic indicators, motivates the literature to switch attention to institutions. Despite its crucial economic implications, there is limited attention on rent-seeking as a driver of economic growth in low-income countries. This paper investigates the effect of rent-seeking on growth in low-income countries from 2004 to 2017using the system generalized method of moments estimator. The empirical results reveal that rent-seeking negatively affects growth, implying that it obstructs the pace of economic development in low-income countries. Hence, it is necessary for policymakers in these countries to adopt anti-rent-seeking policies to promote a rapid and sustainable growth

Cost-Effectiveness of Poly ADP-Ribose Polymerase Inhibitors in Cancer Treatment: A Systematic Review

Background: PARP inhibitors have shown significant improvement in progression-free survival, but their costs cast a considerable financial burden. In line with value-based oncology, it is important to evaluate whether drug prices justify the outcomes. / Objectives: The aim of the study was to systematically evaluate PARP inhibitors on 1) cost-effectiveness against the standard care, 2) impact on cost-effectiveness upon stratification for genetic characteristics, and 3) identify factors determining their cost-effectiveness, in four cancer types. / Methods: We systematically searched PubMed, EMBASE, Web of Science, and Cochrane Library using designated search terms, updated to 31 August 2021. Trial-based or modeling cost-effectiveness analyses of four FDA-approved PARP inhibitors were eligible. Other studies known to authors were included. Reference lists of selected articles were screened. Eligible studies were assessed for methodological and reporting quality before review. / Results: A total of 20 original articles proceeded to final review. PARP inhibitors were not cost-effective as recurrence maintenance in advanced ovarian cancer despite improved performance upon genetic stratification. Cost-effectiveness was achieved when moved to upfront maintenance in a new diagnosis setting. Limited evidence indicated non–cost-effectiveness in metastatic breast cancer, mixed conclusions in metastatic pancreatic cancer, and cost-effectiveness in metastatic prostate cancer. Stratification by genetic testing displayed an effect on cost-effectiveness, given the plummeting ICER values when compared to the “treat-all” strategy. Drug cost was a strong determinant for cost-effectiveness in most models. / Conclusions: In advanced ovarian cancer, drug use should be prioritized for upfront maintenance and for patients with BRCA mutation or BRCAness at recurrence. Additional economic evaluations are anticipated for novel indications

Amalan rewang dalam masyarakat Jawa di Malaysia

Kajian ini dijalankan untuk mengetahui makna amalan rewang dalam masyarakat Jawa dan melihat unsur moden yang sedikit sebanyak telah mengubah cara perlaksanaan tradisi rewang ini. Selain itu, kajian ini juga melihat bagaimana pembahagian tugas dalam rewang serta mengetahui nilai rewang itu terhadap masyarakat Jawa. Kaedah kualitatif secara temubual mendalam dan pemerhatian tidak ikut serta digunakan untuk mendapat maklumat daripada lima orang Jawa yang terlibat dalam amalan rewang seperti tuan rumah, Ketua kampung, ketua masak dan penduduk kampung Lenga yang terlibat dalam aktiviti rewang. Analisis hasil kajian ini dibahagi kepada dua bahagian. Bahagian pertama mengenalpasti makna sebenar amalan rewang dalam masyarakat setempat seperti semangat melakukan kerja bergotong-royong, semangat kerjasama dan identiti masyarakat Jawa itu sendiri. Kemudian, penyerapan unsur moden dalam rewang mempengaruhi cara penyediaan makanan, masakan dan balai atau khemah khawin. Bahagian kedua analisis hasil kajian ini pula tertumpu kepada pembahagian tugas dalam warisan rewang. Tema yang dikaji termasuk aspek melancarkan aktiviti kenduri itu, membina solidariti dalam masyarakat dan menyatupadukan masyarakat yang saling bergantung antara satu sama lain. Di samping itu, antara nilai yang terdapat dalam amalan rewang ini adalah wujudnya nilai tidak mementingkan diri dalam masyarakat Jawa itu sendiri, hormat menghormati, saling muafakat dan wujud nilai perkongsian pengalaman dan emosi dalam masyarakat Jawa di Kampung Jawa, Lenga

CHEMICAL INVESTIGATION AND ANTIPROLIFERATIVE STUDIES OF ISOLATED POLYISOPRENYLATED BENZOPHENONES FROM STEM-BARK OF Garcinia maingayi

In the current study, sequential solvents extraction from the stem bark of Garcinia maingayi, a native plant to Malaysia has led to the isolation of four polyisoprenylated benzophenones: 30-epi-cambogin (GB 1), 14-deoxy-30-epi-cambogin (GB 2), guttiferone F (GB 3), and 14-deoxy-guttiferone F (GB 4). The structures were elucidated using IR, optical rotation, and NMR spectral data. The compounds were evaluated for antiproliferative effect using MTT assay, apoptosis using Annexin V/7-AAD flow cytometry, cell cycle progression, and activation of caspases 3/7, 8 and 9 and BCL2 mRNA expression in MCF-7, HeLa, and HepG2 cancer cell lines. Compounds GB 1 to GB 4 exhibited a remarkable antiproliferative effect on HeLa, MCF-7, and HepG2 cells with IC50 values ranging from 5 to 45 µM. Compounds GB 1 to GB 4 induced significant cell cycle arrest in the G1 phase corroborated with the decrease in the number of MCF-7 and HepG2 cells in S and G2/M phases (P<0.05). Compounds GB 1 to GB 4 induced apoptosis at 48 h. Further, among these, compounds GB 1 and GB 2 induced significant levels of caspases 3 and 9 in HeLa cells, while GB 3 induced caspase 9 activities in both MCF-7 and HepG2 cells. No significant induction of caspase 8 was observed suggesting that the apoptotic effects are mainly mediated through the intrinsic pathway. Only compound GB 1 inhibited the BCL2 mRNA expression significantly in all treated cancer cells. In conclusion, these compounds possess anticancer properties and thus further investigation is crucial on the mechanistic study, structure-activity relationship, and identification of putative molecular targets

Phase 1 Study of High-Specific-Activity I-131 MIBG for Metastatic and/or Recurrent Pheochromocytoma or Paraganglioma

Context: No therapies are approved for the treatment of metastatic and/or recurrent pheochromocytoma or paraganglioma (PPGL) in the United States. Objective: To determine the maximum tolerated dose (MTD) of high-specific-activity I-131 meta-iodobenzylguanidine (MIBG) for the treatment of metastatic and/or recurrent PPGL. Design: Phase 1, dose-escalating study to determine the MTD via a standard 3 + 3 design, escalating by 37 MBq/kg starting at 222 MBq/kg. Setting: Three centers. Patients: Twenty-one patients were eligible, received study drug, and were evaluable for MTD, response, and toxicity. Intervention: Open-label use of high-specific-activity I-131 MIBG therapy. Main Outcome Measures: Dose-limiting toxicities, adverse events, radiation absorbed dose estimates, radiographic tumor response, biochemical response, and survival. Results: The MTD was determined to be 296 MBq/kg on the basis of two observed dose-limiting toxicities at the next dose level. The highest mean radiation absorbed dose estimates were in the thyroid and lower large intestinal wall (each 1.2 mGy/MBq). Response was evaluated by total administered activity: four patients (19%), all of whom received \u3e18.5 GBq of study drug, had radiographic tumor responses of partial response by Response Evaluation Criteria in Solid Tumors. Best biochemical responses (complete or partial response) for serum chromogranin A and total metanephrines were observed in 80% and 64% of patients, respectively. Overall survival was 85.7% at 1 year and 61.9% at 2 years after treatment. The majority (84%) of adverse events were considered mild or moderate in severity. Conclusions: These findings support further development of high-specific-activity I-131 MIBG for the treatment of metastatic and/or recurrent PPGL at an MTD of 296 MBq/kg

Natural products from stem bark of Calophyllum andersonii

Phytochemical study on the stem bark of Calophyllum andersonii has resulted in the isolation of five xanthones, namely (1) caloxanthone I, (2) pyranojacareubin, (3) macluraxanthone, (4) caloxanthone C, and (5) euxanthone. In this study, the compounds were subjected to various spectroscopic analyses including FT-IR, GC-MS, 1D and 2D NMR for structural elucidations. Furthermore, these xanthones were obtained for the first time from Calophyllum andersonii, a plant never reported before. All four extracts, namely hexane, chloroform, ethyl acetate and methanol extracts of the plant showed moderate inhibitions against Bacillus subtilis

H0LiCOW XII. Lens mass model of WFI2033-4723 and blind measurement of its time-delay distance and H0H_0

We present the lens mass model of the quadruply-imaged gravitationally lensed quasar WFI2033-4723, and perform a blind cosmographical analysis based on this system. Our analysis combines (1) time-delay measurements from 14 years of data obtained by the COSmological MOnitoring of GRAvItational Lenses (COSMOGRAIL) collaboration, (2) high-resolution $\textit{Hubble Space Telescope}$ imaging, (3) a measurement of the velocity dispersion of the lens galaxy based on ESO-MUSE data, and (4) multi-band, wide-field imaging and spectroscopy characterizing the lens environment. We account for all known sources of systematics, including the influence of nearby perturbers and complex line-of-sight structure, as well as the parametrization of the light and mass profiles of the lensing galaxy. After unblinding, we determine the effective time-delay distance to be $4784_{-248}^{+399}~\mathrm{Mpc}$, an average precision of $6.6\%$. This translates to a Hubble constant $H_{0} = 71.6_{-4.9}^{+3.8}~\mathrm{km~s^{-1}~Mpc^{-1}}$, assuming a flat $\Lambda$CDM cosmology with a uniform prior on $\Omega_\mathrm{m}$ in the range [0.05, 0.5]. This work is part of the $H_0$ Lenses in COSMOGRAIL's Wellspring (H0LiCOW) collaboration, and the full time-delay cosmography results from a total of six strongly lensed systems are presented in a companion paper (H0LiCOW XIII).Comment: Version accepted by MNRAS. 29 pages including appendix, 17 figures, 6 tables. arXiv admin note: text overlap with arXiv:1607.0140

Exoplanet phase curves: observations and theory

Phase curves are the best technique to probe the three dimensional structure of exoplanets' atmospheres. In this chapter we first review current exoplanets phase curve observations and the particular challenges they face. We then describe the different physical mechanisms shaping the atmospheric phase curves of highly irradiated tidally locked exoplanets. Finally, we discuss the potential for future missions to further advance our understanding of these new worlds.Comment: Fig.5 has been updated. Table 1 and corresponding figures have been updated with new values for WASP-103b and WASP-18b. Contains a table sumarizing phase curve observation