Surrogate science: The idol of a universal method for scientific inference

The application of statistics to science is not a neutral act. Statistical tools have shaped and were also shaped by its objects. In the social sciences, statistical methods fundamentally changed research practice, making statistical inference its centerpiece. At the same time, textbook writers in the social sciences have transformed rivaling statistical systems into an apparently monolithic method that could be used mechanically. The idol of a universal method for scientific inference has been worshipped since the "inference revolution" of the 1950s. Because no such method has ever been found, surrogates have been created, most notably the quest for significant p values. This form of surrogate science fosters delusions and borderline cheating and has done much harm, creating, for one, a flood of irreproducible results. Proponents of the "Bayesian revolution" should be wary of chasing yet another chimera: an apparently universal inference procedure. A better path would be to promote both an understanding of the various devices in the "statistical toolbox" and informed judgment to select among these.

MGMT Promoter Methylation Is a Strong Prognostic Biomarker for Benefit from Dose-Intensified Temozolomide Rechallenge in Progressive Glioblastoma: The DIRECTOR Trial.

PURPOSE: Rechallenge with temozolomide (TMZ) at first progression of glioblastoma after temozolomide chemoradiotherapy (TMZ/RT→TMZ) has been studied in retrospective and single-arm prospective studies, applying temozolomide continuously or using 7/14 or 21/28 days schedules. The DIRECTOR trial sought to show superiority of the 7/14 regimen. EXPERIMENTAL DESIGN: Patients with glioblastoma at first progression after TMZ/RT→TMZ and at least two maintenance temozolomide cycles were randomized to Arm A [one week on (120 mg/m(2) per day)/one week off] or Arm B [3 weeks on (80 mg/m(2) per day)/one week off]. The primary endpoint was median time-to-treatment failure (TTF) defined as progression, premature temozolomide discontinuation for toxicity, or death from any cause. O(6)-methylguanine DNA methyltransferase (MGMT) promoter methylation was prospectively assessed by methylation-specific PCR. RESULTS: Because of withdrawal of support, the trial was prematurely closed to accrual after 105 patients. There was a similar outcome in both arms for median TTF [A: 1.8 months; 95% confidence intervals (CI), 1.8-3.2 vs. B: 2.0 months; 95% CI, 1.8-3.5] and overall survival [A: 9.8 months (95% CI, 6.7-13.0) vs. B: 10.6 months (95% CI, 8.1-11.6)]. Median TTF in patients with MGMT-methylated tumors was 3.2 months (95% CI, 1.8-7.4) versus 1.8 months (95% CI, 1.8-2) in MGMT-unmethylated glioblastoma. Progression-free survival rates at 6 months (PFS-6) were 39.7% with versus 6.9% without MGMT promoter methylation. CONCLUSIONS: Temozolomide rechallenge is a treatment option for MGMT promoter-methylated recurrent glioblastoma. Alternative strategies need to be considered for patients with progressive glioblastoma without MGMT promoter methylation.

Frequent users of the emergency department in a universal health coverage system : a randomized controlled trial of a case-management intervention

BACKGROUND: Frequent emergency department users represent a small number of patients but account for a large number of emergency department visits. They should be a focus because they are often vulnerable patients with many risk factors affecting their quality of life (QoL). Case management interventions have resulted in a significant decrease in emergency department visits, but association with QoL has not been assessed. One aim of our study was to examine to what extent an interdisciplinary case management intervention, compared to standard emergency care, improved frequent emergency department users' QoL. METHODS: Data are part of a randomized, controlled trial designed to improve frequent emergency department users' QoL and use of health-care resources at the Lausanne University Hospital, Switzerland. In total, 250 frequent emergency department users (≥5 attendances during the previous 12 months; ≥ 18 years of age) were interviewed between May 2012 and July 2013. Following an assessment focused on social characteristics; social, mental, and somatic determinants of health; risk behaviors; health care use; and QoL, participants were randomly assigned to the control or the intervention group (n=125 in each group). The final sample included 194 participants (20 deaths, 36 dropouts, n=96 in the intervention group, n=99 in the control group). Participants in the intervention group received a case management intervention by an interdisciplinary, mobile team in addition to standard emergency care. The case management intervention involved four nurses and a physician who provided counseling and assistance concerning social determinants of health, substance-use disorders, and access to the health-care system. The participants' QoL was evaluated by a study nurse using the WHOQOL-BREF five times during the study (at baseline, and at 2, 5.5, 9, and 12 months). Four of the six WHOQOL dimensions of QoL were retained here: physical health, psychological health, social relationship, and environment, with scores ranging from 0 (low QoL) to 100 (high QoL). A linear, mixed-effects model with participants as a random effect was run to analyze the change in QoL over time. The effects of time, participants' group, and the interaction between time and group were tested. These effects were controlled for sociodemographic characteristics and health-related variables (i.e., age, gender, education, citizenship, marital status, type of financial resources, proficiency in French, somatic and mental health problems, and behaviors at risk).

Standardisation process of Universal Mobile Telecommunication System in Third Generation Partnership Project

Third Generation Partnership Project (3GPP) on organisaatio, joka määrittelee ja ylläpitää kolmannen sukupolven matkapuhelinverkon standardeja. Organisaatio luotiin monien eri standardointielinten toimesta havaittaessa, ettei maailmanlaajuista kolmannen sukupolven matkapuhelinteknologiaa voitaisi määritellä ilman laajaa yhteistyötä. 3GPP:ssä standardointityö on jakautunut usealle tekniselle määrittelyryhmälle. Jokaisen ryhmän tehtävänä on kehittää määrittelyjä ja raportteja omalla vastuualueellaan. 3GPP:ssä määrittelytyötä tehdään samanaikaisesti teknillisten määrittelyryhmien välillä. Tämä vaatii tiukkoja sääntöjä määrittelyjen luonti-, hyväksyntä- ja ylläpitotehtäviin. Vain siten on mahdollista hallita määrittelyihin tulevia muutoksia ja tarvittavaa kokonaistyömäärää. Tämä diplomityö kuvaa 3GPP:n määrittelemän UMTS-teknologian. Työssä keskitytään tarkemmin 3GPP-organisaation rakenteeseen, määritysten tekemiseen ja työskentelytapoihin. Tämä diplomityö osoittaa millainen organisaatio ja säännöt vaaditaan maailmanlaajuisen matkapuhelinjärjestelmän kehittämiseen.

Multifactor Performance Study on Complex Systems for the Benefit of Management

The primary objective is to identify the critical factors that have a natural impact on the performance measurement system. It is important to make correct decisions related to measurement systems, which are based on the complex business environment. The performance measurement system is combined with a very complex non-linear factor. The Six Sigma methodology is seen as one potential approach at every organisational level. It will be linked to the performance and financial measurement as well as to the analytical thinking on which the viewpoint of management depends. The complex systems are connected to the customer relationship study. As the primary throughput can be seen in a new well-defined performance measurement structure that will also be facilitated as will an analytical multifactor system. These critical factors should also be seen as a business innovation opportunity at the same time. This master's thesis has been divided into two different theoretical parts. The empirical part consists of both action-oriented and constructive research approaches with an empirical case study. The secondary objective is to seek a competitive advantage factor with a new analytical tool and the Six Sigma thinking. Process and product capabilities will be linked to the contribution of complex system. These critical barriers will be identified by the performance measuring system. The secondary throughput can be recognised as the product and the process cost efficiencies which throughputs are achieved with an advantage of management. The performance measurement potential is related to the different productivity analysis. Productivity can be seen as one essential part of the competitive advantage factor.

Universal Service Policies in Europe & Latam: Evidence on Bridging the Divide in Rural Areas

Broadband access is a key factor for economic and social development. However, providing broadband to rural areas is not attractive to private telecommunications operators due its low or zero investment return. To deal with broadband provision in rural areas, different governance systems based on private and public cooperation have appeared. This paper not only identifies and defines public and private cooperation models but also assesses their impact on overcoming the digital divide in rural areas. The results show that public ownership infrastructure under private management policy has had positive effects on reducing the broadband digital divide and being applied to areas with higher digital divide; subsides to private operators providers only positive effects on reducing broadband digital divide; but public infrastructure with public management programs did not. The results, obtained using quasi-experimental methods, suggest the importance of incentives and control mechanisms in broadband universal service provision plans.

Les vaccins contre le zona : efficacité, sécurité, et rapport coût/bénéfices [Vaccines against Herpes zoster: Effectiveness, safety, and cost/benefit ratio].

CONTEXT: A vaccination against herpes zoster and its complication is available in France since June 2015. Its exact benefit for public health is still controversial and its level of protection is not optimal. All those reasons seem to suggest a low acceptation rate from general practitioners. OBJECTIVE: To evaluate the effectiveness, the safety, and the cost/benefit ratio of the vaccination against herpes zoster in people aged 50 year or over. DOCUMENTARY SOURCE: Systematic review in Medline and PubMed with research by key words: "herpes zoster vaccine", "zoster vaccine" and "post herpetic neuralgia vaccine". SELECTION OF STUDIES: Randomized and observational studies published in English and French language have been selected by two readers. RESULTS: On 1886 articles identified, 62 studies were included in this systematic review of which 21 randomized trials, 21 observational studies, and 17 medico-economic studies concerned the unadjuvanted vaccine. Considered studies showed an effectiveness of 50% against herpes zoster and 60% on post-herpetic neuralgia incidence of the unadjuvanted vaccine. Five randomized controlled studies were identified for the adjuvanted vaccine. The overall effectiveness of this vaccine was > 90% whatever the age of subjects including those over age 70 and 80. The medico-economic studies conducted in many countries have shown that vaccine policies were beneficial in individuals aged 60 years or over. LIMITATION OF THE WORK: Most of data of effectiveness, and tolerance result from 2 large controlled studies only (SPS and ZEST) for the unadjuvanted vaccine and only one for the adjuvanted vaccine. CONCLUSION: Despite controversy and few uncertainties, the vaccine significantly reduces herpes zoster and its complication incidence. In terms of public health objectives, it reduces the burden of the disease and has a positive medico-economic impact. Preliminary data concerning the adjuvanted vaccine, whilst very promising, are still too limited. Up to now, no group of people with particularly high risk of herpes zoster-related complication who will beneficiate the most of the vaccination has been identified yet and only an age criteria has been considered for the recommendation.

Cost-benefit analysis of an enhanced recovery protocol for pancreaticoduodenectomy.

BACKGROUND: Enhanced recovery after surgery (ERAS) programmes have been shown to decrease complications and hospital stay. The cost-effectiveness of such programmes has been demonstrated for colorectal surgery. This study aimed to assess the economic outcomes of a standard ERAS programme for pancreaticoduodenectomy. METHODS: ERAS for pancreaticoduodenectomy was implemented in October 2012. All consecutive patients who underwent pancreaticoduodenectomy until October 2014 were recorded. This group was compared in terms of costs with a cohort of consecutive patients who underwent pancreaticoduodenectomy between January 2010 and October 2012, before ERAS implementation. Preoperative, intraoperative and postoperative real costs were collected for each patient via the hospital administration. A bootstrap independent t test was used for comparison. ERAS-specific costs were integrated into the model. RESULTS: The groups were well matched in terms of demographic and surgical details. The overall complication rate was 68 per cent (50 of 74 patients) and 82 per cent (71 of 87 patients) in the ERAS and pre-ERAS groups respectively (P = 0·046). Median hospital stay was lower in the ERAS group (15 versus 19 days; P = 0·029). ERAS-specific costs were euro922 per patient. Mean total costs were euro56 083 per patient in the ERAS group and euro63 821 per patient in the pre-ERAS group (P = 0·273). The mean intensive care unit (ICU) and intermediate care costs were euro9139 and euro13 793 per patient for the ERAS and pre-ERAS groups respectively (P = 0·151). CONCLUSION: ERAS implementation for pancreaticoduodenectomy did not increase the costs in this cohort. Savings were noted in anaesthesia/operating room, medication and laboratory costs. Fewer patients in the ERAS group required an ICU stay.

Cardiovascular risk among hypertensive adolescents and the potential benefit of a screen-and-treat strategy.

To evaluate whether screening for hypertension should start early in life, information on the risk of diseases associated with the level of blood pressure in childhood or adolescence is needed. The study by Leiba et al. that is reported in the current issue of Pediatric Nephrology demonstrates convincingly that hypertensive adolescents are at higher risk of cardiovascular death than normotensive adolescents. Nevertheless, it can be shown that this excess risk is not sufficient to justify a screen-and-treat strategy. Since the large majority of cardiovascular deaths occur among normotensive adolescents, measures for primordial prevention of cardiovascular diseases could have a much larger impact at the population level.

Brideshead Revisited (1945) by Evelyn Waugh (1903-1966): the benefit of an Arcadian experience in confronting the human tragedy

As the frontispiece of Book One of Evelyn Waugh’s Brideshead Revisited, the phrase ‘Et in Arcadia ego’ announces the author’s intention of making the classical Arcadian theme a key reference in a text that speaks of nostalgia for a joyful past in times marked by sadness and pain. However, an interpretation may be approached from several directions even within the classical tradition. Thus, without ignoring philological or artistic aspects of the topic, this article focuses on a close study of the author’s most original message: the notion that a youthful Arcadian experience confers on young men and women a ‘residue of happiness’ able to sustain their future development and assist them in dealing with the challenges of personal tragedy.