Optimistic Analysis Research Articles

Blinded independent central review versus local investigator assessment of PFS in RCTs of immunotherapy in advanced cancers: A systematic review and meta-analysis

BackgroundAssessment of Progression-free survival (PFS) events by investigators might be inaccurate in randomized controlled trials (RCTs) with open-label design. We explored differences in PFS evaluated by blinded independent central review (BICR) or local investigator assessment (IA) in trials testing immunotherapy (IO) in advanced cancers. MethodsWe systematically reviewed articles of RCTs investigating IO in advanced tumors, published in PubMed-indexed journals up to December 2023. For each RCT, we collected PFS results by BICR and by local IA. We calculated the discrepancy index (DI) as the ratio of BICR and IA Hazard Ratios (HRBICR/HRIA) for PFS. An overall DI and relative confidence interval (CI) were calculated using a fixed-effect model weighted for the inverse of variance. FindingsOnly 32/140 (22.9 %) RCTs reported both BICR and local IA PFS data, including 17,054 patients. PFS was the sole primary endpoint in 19/32 (59.4 %) and a co-primary endpoint 9/32 (28.2 %) trials. The study design was open label or double-blind in 17/32 (53.1 %) and 15/32 (46.9 %) RCTs, respectively. The overall DI was 1.07 (95 % CI 1.01–1.13; I2 =0, p = 0.02), revealing a more optimistic analysis of results in favor of local IA. In the 17 open-label trials, the overall DI was 1.09 (95 % CI 1.02–1.17, I2 =0, p = 0.02), revealing a more favorable interpretation of PFS results by local investigators. InterpretationWe found a statistically significant difference between BICR and local IA of PFS in trials of IO in cancer. These results suggest that the double assessment is recommended in RCTs testing IO, especially in open-label trials. FundingThis work was supported by the MFAG27826–2022 grant (Dr. Alberto Servetto).

Analysis of the behavior of piled foundations in unconventional soil

Building foundations using pile groups generally assume that the piles absorb the entire load of the structure. However, it is known that pile caps rest not only on the piles but also on the surrounding soil. These foundations involve great complexity in the phenomenon of load sharing, especially when they are situated on unconventional soils, such as tropical climate soils. To study this behavior, static load tests were conducted on real foundations. These tests were also used to calibrate a three-dimensional finite element numerical model (FEA-3D) using Rocscience's RS3 software. The results showed that the settlement corresponding to the allowable load of the pile groups was significantly lower, ranging from 22 % to 73 %, compared to pile caps that exert contact pressure on the soil. For pile groups, the efficiency ranged between 92 % and 109 %, while for pile caps with contact, it ranged from 132 % to 178 %. In this sense, it becomes evident that estimating the settlement of the pile group based on the conventional design, which does not consider the contact between the cap and the soil, can significantly underestimate the settlement, and provide an overly optimistic analysis of the soil-structure interaction.

Classification and Parametric Analysis of Solar Hybrid PVT System: A Review

A Hybrid Photovoltaic Thermal (PVT) system is one of the most emerging and energy-efficient technologies in the area of solar energy engineering. This review paper provides a comprehensive review of hybrid PVT systems in the context of the history of PVT, general classification, and parameter analysis. Several cell technologies with spectrum analysis are discussed to understand the application’s ability and energy efficiency. Hybrid PVT concept, characteristics, and structure analysis is also discussed in this study. An extensive analysis on the classifications of hybrid PVT systems from the recent literature is also presented here. These literatures are identified based on several criteria. In order to provide a complete and energy-efficient technology, an innovative classification of the hybrid PVT system is proposed in this paper. This proposed classification is a combination and upgrade of various existing classifications mentioned in recent research studies. Parameters have a significant and unavoidable impact on the performance and efficiency of the hybrid PVT system. A brief analysis of different parameters and the optimization of the system is conducted after reviewing recent research articles. This analysis provides insights into the impact of parameter variations on the system. A novel parameter model comprising parametric and optimistic analyses is also presented in this paper. It provides a detailed parametric description that significantly affects the performance and efficiency of the hybrid PVT system. Finally, the assessment focuses on a critical analysis of the main challenges in adopting PVT technology and suggests ways to overcome these barriers.

Can Distributed Intermittent Renewable Generation Reduce Future Grid Investments? Evidence from France

Abstract This paper estimates the relationship between investments in five distributed generation technologies and hourly net withdrawals from over 2,000 electricity distribution networks in France between 2005 and 2018. We find that investments in distributed wind and solar generation have little or no impact on the annual peak of hourly net withdrawals from the distribution grid, while investments in hydroelectric and thermal distributed generation significantly reduce it. An optimistic analysis of the impact of investments in battery storage suggests that high levels are required for distributed wind and solar to deliver similar reductions in the annual peak of hourly net withdrawals. Our results imply that public policies favoring distributed wind and solar generation over utility-scale generation cannot be rationalized by savings in future grid investments.

The Firebird and the Fox: Russian Culture under the Tsars and Bolsheviks by Jeffrey Brooks

Reviewed by: The Firebird and the Fox: Russian Culture under the Tsars and Bolsheviks by Jeffrey Brooks Svetlana Yefimenko The Firebird and the Fox: Russian Culture under the Tsars and Bolsheviks. By Jeffrey Brooks. Cambridge: Cambridge University Press. 2019. vii+330 pp. £29.99. ISBN 978–1–108–48446–6. The fraught century between 1850 and 1950 was driven in Russia by radical transformations in politics, social structure, economic activity, and religious practice. How these upheavals manifested in the cultural production of the time—namely, literature, art, music, and dance—is the subject of Jeffrey Brooks's The Firebird and the Fox. By helpfully arranging what he terms the 'creative century' into three periods, Brooks focuses his socio-politically and economically informed lens on the culture of each epoch. First, on how the arts responded to emancipation and reform between 1850 and 1889; next, dialogue between revolutionary politics and art from 1890 to 1916; and, finally, artistic expression under the Soviet regime from 1917 to 1950. Each section subscribes to Brooks's overarching theme: the opposition of firebird and fox, both ubiquitous folkloric figures in Russian nineteenth- and twentieth-century culture. With a nod to Isaiah Berlin's archetypal hedgehog and fox (The Hedgehog and the Fox (London: Weidenfeld and Nicolson, 1953)), Brooks's dyad is introduced here as a poetic, rather than strictly rigorous, organizing principle. The dazzling firebird and the sly vixen invoke, respectively, the soaring imagination and practical wisdom that characterized Russian cultural production in this rapidly evolving, and often violent, political landscape. The first section of Brooks's monograph describes with lyricism and humour the raffish bandits, rebels, Holy Fools, and ordinary folk represented in the lubki (woodcuts), adventure novels, and print magazines that circulated widely between 1850 and 1889, reassuring the reader that the boundary between anarchy and order was always re-established in the end: '[F]ree spaces proved uninhabitable over the longer period. People must return to the realm of society and the law, where rebels may face punishment and death or win redemption' (p. 43). This formulation explains why popular fiction of the day embraced Christian kenoticism, why Gogolʹ and Turgenev extolled freedom, and why Dostoevskii and Tolstoi were preoccupied with spiritual salvation. It does not, however, explain Chekhov, who is shown to remain ambivalent to the last, and who, along with Tolstoi, helped inaugurate a tradition of civic obligation and activism among Russia's cultural producers that continues to this day. Brooks turns in the second section to the last days of empire and the new art forms emerging in an expanding market economy. As the tsarist regime struggled to maintain power through rhetoric and, when that failed, summary executions, Modernism, neo-Realism, and celebrity culture flourished, with experimental artists such as Mikhail Vrubelʹ and Natalia Goncharova on the ascendant. Realist writers such as Maksim Gorʹkii gradually fell out of vogue, replaced by Symbolism and satire. Brooks recounts how the innovations of Sergei [End Page 521] Diaghilev, Igorʹ Stravinskii, and the legendary Ballets Russes repositioned artists as beneficiaries, rather than critics, of autocracy. As art and empire collaborated to legitimize themselves by exporting Russia's artistic achievements, many avantgarde artists distanced themselves from the sense of collective responsibility that Chekhov, Tolstoi, and Gorʹkii had embraced: '[T]he best young artists of the early twentieth century [. . .] rejected the obligation to enlighten' (p. 148). Adopting the ambivalence of his vulpine hero, Brooks remains refreshingly free from judgement, neither condemning nor praising his subjects. Brooks's tolerance informs his survey of post-1917 cultural production, which studies how the economic and political realities of the New Economic Policy, Stalin's Five-Year Plan, and the Great Terror, along with tightening ideological control over the arts, contributed to one of the most dazzling periods in Russian intellectual history. This seeming paradox justifies Brooks's optimistic analysis of what cultural figures such as Kazimir Malevich and Vladimir Maiakovskii saw as 'a new art for the Soviet people' (p. 168). Even in those hard times, poets, writers, artists, composers, film-makers, and cartoonists rallied to find unique avenues for subversion, self-expression, and even joy. Brooks describes how artists such as Vladimir Tatlin...

Against Abstractions

Abstract This article focuses on different iterations of virality to explore the racial logic of death and the crisis of our time during the coronavirus pandemic. By examining the war on the coronavirus, the sanctions on Iran, and the rise of white supremacy in the United States, this article argues that the optimistic analyses of virus and virality are predicated upon the abstraction of the human, thus overlooking race and geopolitics.

Cumulative live birth rates for low-prognosis women over 5\u2009years or 9 frozen-thawed embryo transfer cycles

BackgroundFor heterogeneous populations of low-prognosis women, it remains unclear as to how long individuals should continue undergoing ART when attempting to have a baby, as there have been insufficient studies to date tracking the cumulative live birth rates (CLBRs) for these women over the entire course of their ART treatment, particularly over extended time periods.MethodsThis was a retrospective analysis of 17,698 women at a tertiary care academic medical center who had begun undergoing IVI/ICSI cycles using a progestin-primed ovarian stimulation (PPOS) approach between January 2013 and January 2019. Low-prognosis patients were stratified into four groups based upon POSEIDON criteria, with patients exhibiting normal or high ovarian reserves and response to stimulation (defined as AFC ≥5, > 9 oocytes retrieved) being included as controls (group 5). The CLBR within 5 years or 9 FET cycles from the ovum pick-up (OPU) day of the first cycle was the primary endpoint for this study, including all repetitive oocyte retrieval cycles and subsequent FET cycles. Optimistic and conservative approaches were used for the analysis of CLBRs and the depiction of cumulative incidence curves.ResultsUnder both optimistic and conservative model analyses, normal and good responders exhibited the highest CLBR within 5 years or 9 FET cycles, followed by younger unexpected poor responders, younger expected poor responders, older unexpected poor responders, and older expected poor responders. Upward trends in CLBRs were evident across the five groups with the prolongation of time or an increase in FET cycle counts. Within the first 2 years or 3 FET cycles, the CLBRs rose rapidly, followed by more moderate increases over the following 2–3.5 years or 4–6 cycles, with expected poor responders exhibiting the most obvious improvements. All Patients reached a CLBR plateau after 3.5 years or 6 FET cycles.ConclusionsAll low-prognosis women should undergo ART treatment for a minimum of 2 years or 3 FET cycles, and exhibit better outcomes when extending ART treatment to 3.5 years or 6 FET cycles (particularly for POSEIDON groups 3 and 4), but should consider ceasing further treatment thereafter due to a lack of apparent benefit.

Working for your own folks: the microeconomics of social media

ABSTRACT This paper uses a comparative ethnographic approach to explore the ways in which social media enables new economic strategies that capitalize on women's traditional forms of reliance within their local communities. We use ethnographic examples from northern Chile, southeast Italy, and south India to show how women are successful in establishing small but prestigious entrepreneurial activities by using social media to respond to local social and cultural needs. Women use social media to transform both conventional work practices and individuals' notions of work in ways that overcome important structural constraints they face in their respective communities. These findings contrast with optimistic analyses that suggest online platforms decrease global inequalities through bringing disadvantaged people into global economic flows. This article demonstrates the effective ways in which individuals use social media to gradually change local norms related to gender and work while making small but important gains towards economic stability. This process is related to important shifts in sociality that have resulted from social media use within local communities. By focusing on entrepreneurship and gendered aspects of online economic exchange, we develop an understanding of what happens when longstanding expectations for gendered work meet commerce made possible through new media.

Prospective comparison of 18F-PSMA-1007 PET/CT, whole-body MRI and CT in primary nodal staging of unfavourable intermediate- and high-risk prostate cancer

PurposeTo prospectively compare 18F-prostate-specific membrane antigen (PSMA)-1007 positron emission tomography (PET)/CT, whole-body magnetic resonance imaging (WBMRI) including diffusion-weighted imaging (DWI) and standard computed tomography (CT), in primary nodal staging of prostate cancer (PCa).MethodsMen with newly diagnosed unfavourable intermediate- or high-risk PCa prospectively underwent 18F-PSMA-1007 PET/CT, WBMRI with DWI and contrast-enhanced CT within a median of 8 days. Six readers (two for each modality) independently reported pelvic lymph nodes as malignant, equivocal or benign while blinded to the other imaging modalities. Sensitivity, specificity and accuracy were reported according to optimistic (equivocal lesions interpreted as benign) and pessimistic (equivocal lesions interpreted as malignant) analyses. The reference standard diagnosis was based on multidisciplinary consensus meetings where available histopathology, clinical and follow-up data were used.ResultsSeventy-nine patients completed all the imaging modalities, except for one case of interrupted WBMRI. Thirty-one (39%) patients had pelvic lymph node metastases, which were detected in 27/31 (87%), 14/31 (45%) and 8/31 (26%) patients by 18F-PSMA-1007 PET/CT, WBMRI with DWI and CT, respectively (optimistic analysis). In 8/31 (26%) patients, only 18F-PSMA-1007 PET/CT detected malignant lymph nodes, while the other two imaging modalities were reported as negative. At the patient level, sensitivity and specificity values for 18F-PSMA-1007 PET/CT, WBMRI with DWI and CT in optimistic analysis were 0.87 (95%CI 0.71–0.95) and 0.98 (95%CI 0.89–1.00), 0.37 (95%CI 0.22–0.55) and 0.98 (95%CI 0.89–1.00) and 0.26 (95%CI 0.14–0.43) and 1.00 (95%CI 0.93–1.00), respectively.Conclusion18F-PSMA-1007 PET/CT showed significantly greater sensitivity in nodal staging of primary PCa than did WBMRI with DWI or CT, while maintaining high specificity.Clinical trial registrationClinicaltrials.gov ID: NCT03537391

What Kinds of Distributed Generation Technologies Defer Network Expansions? Evidence from France

This paper estimates the relationship between investments in five distributed generation technologies and hourly net injections to the distribution grid for over 2,000 substations in France between 2005 and 2018. We find that investments in distributed wind and solar capacity have little or no impact on the annual peak of hourly net injections to the distribution grid, while investments in hydroelectric and thermal distributed generation significantly reduce it. An optimistic analysis of battery storage suggests that high levels of investments are required for distributed wind and solar investments to deliver similar reductions in the annual peak of hourly net injections.

Às voltas com o futuro: Minhas incursões na Educação Física Escolar.

Este Ensaio, construído em momento ímpar na história atual do mundo contemporâneo, onde incertezas sobre nosso presente e futuro prevalecem às análises mais otimistas sobre eles, traz reflexões acerca da Educação Física Escolar brasileira a partir das incursões no tema realizadas pelo autor ao longo de sua trajetória profissional, alicerçada em mais de quatro décadas de atuação. Em cenário de pandemia sanitária mundial motivada pelo Covid-19, e pandemônio nacional causado por desastrosas ações políticas do governo federal de nosso país, motivadoras de instabilidade de nossas instituições republicanas, coloca em evidência a política educacional e, nela, a perspectiva que redundou caber à EF Escolar ao longo do tempo passado e presente, deixando em perspectiva seu lugar em futuro próximo.

A Prospective Comparison of 18F-prostate-specific Membrane Antigen-1007 Positron Emission Tomography Computed Tomography, Whole-body 1.5 T Magnetic Resonance Imaging with Diffusion-weighted Imaging, and Single-photon Emission Computed Tomography/Computed Tomography with Traditional Imaging in Primary Distant Metastasis Staging of Prostate Cancer (PROSTAGE)

BackgroundComputed tomography (CT) and bone scintigraphy (BS) are the imaging modalities currently used for distant metastasis staging of prostate cancer (PCa). ObjectiveTo compare standard staging modalities with newer and potentially more accurate imaging modalities. Design, setting, and participantsThis prospective, single-centre trial (NCT03537391) enrolled 80 patients with newly diagnosed high-risk PCa (International Society of Urological Pathology grade group ≥3 and/or prostate-specific antigen [PSA] ≥20 and/or cT ≥ T3; March 2018–June 2019) to undergo primary metastasis staging with two standard and three advanced imaging modalities. Outcome measurements and statistical analysisThe participants underwent the following five imaging examinations within 2 wk of enrolment and without a prespecified sequence: BS, CT, 99mTc-hydroxymethylene diphosphonate (99mTc-HMDP) single-photon emission computed tomography (SPECT)-CT, 1.5 T whole-body magnetic resonance imaging (WBMRI) using diffusion-weighted imaging, and 18F-prostate-specific membrane antigen-1007 (18F-PSMA-1007) positron emission tomography(PET)-CT. Each modality was reviewed by two independent experts blinded to the results of the prior studies, who classified lesions as benign, equivocal, or malignant. Pessimistic and optimistic analyses were performed to resolve each equivocal diagnosis. The reference standard diagnosis was defined using all available information accrued during at least 12 mo of clinical follow-up. Patients with equivocal reference standard diagnoses underwent MRI and/or CT to search for the development of anatomical correspondence. PSMA PET-avid lesions without histopathological verification were rated to be malignant only if there was a corresponding anatomical finding suspicious for malignancy at the primary or follow-up imaging. Results and limitationsSeventy-nine men underwent all imaging modalities except for one case of interrupted MRI. The median interval per patient between the first and the last imaging study was 8 d (interquartile range [IQR]: 6–9). The mean age was 70 yr (standard deviation: 7) and median PSA 12 ng/mL (IQR:7–23). The median follow-up was 435 d (IQR: 378–557). Metastatic disease was detected in 20 (25%) patients. The imaging modality 18F-PSMA-1007 PET-CT had superior sensitivity and highest inter-reader agreement. The area under the receiver-operating characteristic curve (AUC) values for bone metastasis detection with PSMA PET-CT were 0.90 (95% confidence interval [CI]: 0.85–0.95) and 0.91 (95% CI: 0.87–0.96) for readers 1 and 2, respectively, while the AUC values for BS, CT, SPECT-CT, and WBMRI were 0.71 (95% CI: 0.58–0.84) and 0.8 (95% CI: 0.67–0.92), 0.53 (95% CI: 0.39–0.67) and 0.66 (95% CI: 0.54–0.77), 0.77 (95% CI: 0.65–0.89) and 0.75 (95% CI: 0.62–0.88), and 0.85 (95% CI: 0.74–0.96) and 0.67 (95% CI: 0.54–0.80), respectively, for the other four pairs of readers. The imaging method 18F-PSMA-1007 PET-CT detected metastatic disease in 11/20 patients in whom standard imaging was negative and influenced clinical decision making in 14/79 (18%) patients. In 12/79 cases, false positive bone disease was reported only by PSMA PET-CT. Limitations included a nonrandomised study setting and few histopathologically validated suspicious lesions. ConclusionsDespite the risk of false positive bone lesions, 18F-PSMA-1007 PET-CT outperformed all other imaging methods studied for the detection of primary distant metastasis in high-risk PCa. Patient summaryIn this report, we compared the diagnostic performance of conventional and advanced imaging. It was found that 18F-prostate-specific membrane antigen-1007 positron emission tomography/computed tomography (18F-PSMA-1007 PET-CT) was superior to the other imaging modalities studied for the detection of distant metastasis at the time of initial diagnosis of high-risk prostate cancer. PSMA PET-CT also appears to detect some nonmetastatic bone lesions.

‘Lions led by donkeys’? Britain’s war in Afghanistan, 2001–2014

This article argues that Theo Farrell’s book Unwinnable is a semi-official British Army history of the Afghan war and reflects the ‘dominant military narrative’. The book’s argument is contradictory, it suggests that NATO was ‘learning, adapting and winning’ the war but the politicians stabbed the military in the back by withdrawing just as a turning point had been reached in 2009-11. This was Farrell’s optimistic analysis when the war was ongoing. But Unwinnable also argues that the war was unwinnable from 2001. This implies that it was the military elite that blundered because of their enthusiasm for the escalation of Britain’s involvement in an unwinnable and, therefore, futile war. Unwinnable tries to rescue ‘counterinsurgency’ by trying to claim, implausibly, that it was only properly implement during 2009-11. Farrell champions the empowerment of the military elite and is unconcerned that the politicians struggled to exert democratic control over the military.

MP62-18 PRIMARY METASTASIS STAGING USING 18 F-PSMA-1007 PET-CT IN HIGH-RISK PROSTATE CANCER

MP62-18 PRIMARY METASTASIS STAGING USING ¹⁸ F-PSMA-1007 PET-CT IN HIGH-RISK PROSTATE CANCER

Computing the Geometric Intersection Number of Curves

The geometric intersection number of a curve on a surface is the minimal number of self-intersections of any homotopic curve, i.e., of any curve obtained by continuous deformation. Given a curve c represented by a closed walk of length at most ℓ on a combinatorial surface of complexity n , we describe simple algorithms to (1) compute the geometric intersection number of c in O ( n + ℓ 2 ) time, (2) construct a curve homotopic to c that realizes this geometric intersection number in O ( n +ℓ 4 ) time, and (3) decide if the geometric intersection number of c is zero, i.e., if c is homotopic to a simple curve, in O ( n +ℓ log ℓ) time. The algorithms for (2) and (3) are restricted to orientable surfaces, but the algorithm for (1) is also valid on non-orientable surfaces. To our knowledge, no exact complexity analysis had yet appeared on those problems. An optimistic analysis of the complexity of the published algorithms for problems (1) and (3) gives at best a O ( n + g 2 ℓ 2 ) time complexity on a genus g surface without boundary. No polynomial time algorithm was known for problem (2) for surfaces without boundary. Interestingly, our solution to problem (3) provides a quasi-linear algorithm to a problem raised by Poincaré more than a century ago. Finally, we note that our algorithm for problem (1) extends to computing the geometric intersection number of two curves of length at most ℓ in O ( n + ℓ 2 ) time.

Primary Metastasis Staging Using 18F-PSMA-1007 PET-CT in High-Risk Prostate Cancer: A Prospective Comparative Study of Advanced and Traditional Imaging Modalities

Background: Computed tomography (CT) and bone scintigraphy are the imaging modalities currently used for primary metastasis staging of high-risk prostate cancer (PCa). This trial compared these standard staging modalities with potentially more accurate imaging modalities: single photon emission computed tomography-CT (SPECT-CT), magnetic resonance imaging (MRI), prostate specific membrane antigen positron emission tomography (PSMA PET). Methods: This prospective, registered, single-centre, open-label, single-arm trial enrolled patients with primary high-risk PCa. Results of bone scintigraphy and CT were compared with 99mTc-HMDP SPECT-CT, 1.5T whole-body MRI using diffusion-weighted imaging and 18 F-PSMA-1007 PET-CT. Each imaging modality was reviewed by two independent experts blinded for the other modalities. The lesions were classified as benign, equivocal or malignant. Pessimistic and optimistic analyses were performed to resolve equivocal lesion status. Based on clinical data, including follow-up investigations, the best valuable comparator was defined at lesion level in multidisciplinary consensus meetings. Findings: 79 men were included and underwent all imaging modalities, except for one cancelled MRI due to claustrophobia. Mean age was 70 years and median PSA 12 ng/ml (range: 3-2000). Metastatic disease was detected in 27 (34%) patients. In pessimistic and optimistic analysis at patient, region and lesion levels, PSMA PET-CT was superior to all other modalities concerning sensitivity, and the area under curve values (AUC) at the bone region, while maintaining high specificity and demonstrating the highest inter-reader agreement. AUC for detection of bone metastasis for PSMA PET-CT was 0·94 (95%Cl;0·90-0·99) and 0·96 (95%CI;0·92-0·99) (reader 1, and reader 2, respectively) while AUC for all other modalities was in the range of 0·55-0·76. PSMA PET-CT revealed metastatic disease in 18/27 patients where standard imaging was negative. Interpretation: 18F-PSMA-1007 PET-CT outperformed other imaging methods in primary metastasis staging of high-risk PCa. We recommend further evaluation of this method as a new reference standard. Trial Registration number: (ClinicalTrials.gov NCT03537391). Funding Statement: This study was financially supported by grants from Finnish Government Research and Development Funds for Medical Research, Turku University Hospital and TYKS-SAPA Research Fund. Declaration of Interests: Dr. Anttinen reports grants from Profound Medical Inc, Finnish Urological Research Foundation and Finnish Urological Association, outside the submitted work. Dr. Ettala reports non-financial support from Ferring Pharmaceuticals Inc, SwanMedica and Pierre-Fabre Pharma Norden AB, and personal fees from Astellas, outside the submitted work. Dr. Sandell reports personal fees from Roche, outside the submitted work. Dr. Taimen reports personal fees from Roche, AstraZeneca and MSD, and non-financial support from MSD, all outside the submitted work. Dr. Bostrom reports grants from the Cancer Foundation Finland, personal fees from Profound Medical Inc and Janssen-Cilag Company, outside the submitted work. The other authors declare that there is no conflict of interest regarding the publication of this article. Ethical Approval Statement: The trial protocol, included in the Supplemental material, was approved by the ethics committee of the Hospital District of Southwest Finland, and written informed consent was obtained from all participants. The trial was performed in accordance with the principles of the Declaration of Helsinki.

A Prospective Study Comparing 99mTc-Hydroxyethylene-Diphosphonate Planar Bone Scintigraphy and Whole-Body SPECT/CT with 18F-Fluoride PET/CT and 18F-Fluoride PET/MRI for Diagnosing Bone Metastases.

We prospectively evaluated and compared the diagnostic performance of 99mTc-hydroxyethylene-diphosphonate (99mTc-HDP) planar bone scintigraphy (pBS), 99mTc-HDP SPECT/CT, 18F-NaF PET/CT, and 18F-NaF PET/MRI for the detection of bone metastases. Methods: One hundred seventeen patients with histologically proven malignancy referred for clinical pBS were prospectively enrolled. pBS and whole-body SPECT/CT were performed followed by 18F-NaF PET/CT within 9 d. 18F-NaF PET/MRI was also performed in 46 patients. Results: Bone metastases were confirmed in 16 patients and excluded in 101, which was lower than expected. The number of equivocal scans was significantly higher for pBS than for SPECT/CT and PET/CT (18 vs. 5 and 6, respectively; P = 0.004 and 0.01, respectively). When equivocal readings were excluded, no statistically significant difference in sensitivity, specificity, positive predictive value, negative predictive value, or overall accuracy were found when comparing the different imaging techniques. In the per-patient analysis, equivocal scans were either assumed positive for metastases ("pessimistic analysis") or assumed negative for metastases ("optimistic analysis"). The percentages of misdiagnosed patients for the pessimistic analysis were 21%, 15%, 9%, and 7% for pBS, SPECT/CT, PET/CT, and PET/MRI, respectively. Corresponding figures for the optimistic analysis were 9%, 12%, 5%, and 7%. In those patients identified as having bone metastases according to the reference standard, SPECT/CT, 18F-NaF PET/CT, and PET/MRI detected additional lesions compared with pBS in 31%, 63%, and 71%, respectively. Conclusion:18F-NaF PET/CT and whole-body SPECT/CT resulted in a significant reduction of equivocal readings compared with pBS, which implies an improved diagnostic confidence. However, the clinical benefit of using, for example, 18F-NaF PET/CT or PET/MRI as compared with SPECT/CT and pBS in this patient population with a relatively low prevalence of bone metastases (14%) is likely limited. This conclusion is influenced by the low prevalence of patients with osseous metastases. There may well be significant differences in the sensitivity of SPECT/CT, PET/CT, and PET/MRI compared with pBS, but a larger patient population or a patient population with a higher prevalence of bone metastases would have to be studied to demonstrate this.

Civil society and small town capitalism: the case of Arni

The paper explores the impact of civil society on India’s capitalist development. While the concept of civil society is controversial, the interpretations of the phenomenon can be reduced to two major views. The first view builds on the optimistic analysis by Alexis de Tocqueville, who introduces the idea of civil society as a partnership of equal individuals that promote the common good, and the second view builds on the analysis by Antonio Gramsci, who sees civil society as the organization that supports the hegemony of the dominant classes pursuing particularistic interests. The paper focuses on India’s civil society having in mind these alternative views in order to explore which one of the two fits better to the case. The paper builds on the hypothesis that, due to the widespread informality of India’s economy, the associations of civil society are a major character in India’s society, playing a crucial regulative role in substitution of the state, and that the analysis of civil society enhances the understanding of capitalist organization and of the power relations governing it. The argument is that it is hardly appropriate to interpret India’s organized society as ‘good’ civil society, while the Gramscian interpretation appears to be more appropriate to the Indian case in which the organizations of civil society are the tools to regulate the economy, managing interest conflicts and building social consensus over the hegemony of the elites. The argument is supported with evidence coming from Arni, a market town in Provincial India in which the economy is vastly informalized and the market is not the prevailing organizing principle, while institutions and structures produced in civil society regulate economic transactions.

Are interventions to increase the uptake of screening for cardiovascular disease risk factors effective? A systematic review and meta-analysis

BackgroundCardiovascular disease (CVD) is the leading cause of death globally. However, many individuals are unaware of their CVD risk factors. The objective of this systematic review is to determine the effectiveness of existing intervention strategies to increase uptake of CVD risk factors screening.MethodsA systematic search was conducted through Pubmed, CINAHL, EMBASE and Cochrane Central Register of Controlled Trials. Additional articles were located through cross-checking of the references list and bibliography citations of the included studies and previous review papers. We included intervention studies with controlled or baseline comparison groups that were conducted in primary care practices or the community, targeted at adult populations (randomized controlled trials, non-randomized trials with controlled groups and pre- and post-intervention studies). The interventions were targeted either at individuals, communities, health care professionals or the health-care system. The main outcome of interest was the relative risk (RR) of screening uptake rates due to the intervention.ResultsWe included 21 studies in the meta-analysis. The risk of bias for randomization was low to medium in the randomized controlled trials, except for one, and high in the non-randomized trials. Two analyses were performed; optimistic (using the highest effect sizes) and pessimistic (using the lowest effect sizes). Overall, interventions were shown to increase the uptake of screening for CVD risk factors (RR 1.443; 95% CI 1.264 to 1.648 for pessimistic analysis and RR 1.680; 95% CI 1.420 to 1.988 for optimistic analysis). Effective interventions that increased screening participation included: use of physician reminders (RR ranged between 1.392; 95% CI 1.192 to 1.625, and 1.471; 95% CI 1.304 to 1.660), use of dedicated personnel (RR ranged between 1.510; 95% CI 1.014 to 2.247, and 2.536; 95% CI 1.297 to 4.960) and provision of financial incentives for screening (RR 1.462; 95% CI 1.068 to 2.000). Meta-regression analysis showed that the effect of CVD risk factors screening uptake was not associated with study design, types of population nor types of interventions.ConclusionsInterventions using physician reminders, using dedicated personnel to deliver screening, and provision of financial incentives were found to be effective in increasing CVD risk factors screening uptake.

Spontaneous pregnancy in Turner's Syndrome: An optimistic analysis

Searchable abstracts of presentations at key conferences in endocrinology ISSN 1470-3947 (print) | ISSN 1479-6848 (online)