Aging and the governance of the healthcare system in Japan. Bruegel Working Paper 2014/14, December 2014

Japan is the most rapidly aging country in the world. This is evidence that the social security system, which consists of the pension system, healthcare system and other programmes, has been working well. The population is shrinking because of a falling birth rate. It is expected that the population will fall from 128 million in 2010 to 87 million in 2060. During this period, the ratio of people aged 65 or over will rise from 23 percent to 39.9 percent. Japan’s age dependency ratio was 62 in 2013, the highest among advanced nations. It is expected to rise sharply to 94 in 2050 (see Figure 1 on page 4). A total reform of the Japanese social security system, therefore, is inevitable. From the point of view of fiscal reconstruction, reform of the healthcare system is the most important issue. The biggest problem in the healthcare system is that both the funding system and the care-delivery system are extremely fragmented. The government is planning its reform of the healthcare system based on the principle of integration. Other advanced economies could learn from the Japanese experience.

How returns from tertiary education differ by field of study. Implications for policy-makers and students. CEPS Working Document No. 411/July 2015

With the huge growth in enrolment in higher education, the key question facing young people today is not so much “what to study” as “whether to study”. Taking a methodologically innovative approach, this paper measures the net present value of university education and compares returns from studying a range of different subjects. We use data from 5 European countries (France, Italy, Hungary, Poland and Slovenia) and include (opportunity) costs in the computation. Results suggest that enrolling in science, technology, engineering and mathematics (STEM) courses is often not the best investment for students, especially female students. In choosing what to study, therefore, students are taking decisions that are consistent with their own private returns. This suggests that policymakers should consider changing the incentives offered if they wish to change students’ behaviour.

Overtreatment of asymptomatic bacteriuria: a qualitative study

BACKGROUND Overtreatment of asymptomatic bacteriuria (ASB) is widespread and may result in antibiotic side-effects, excess costs to the healthcare system, and may potentially trigger antimicrobial resistance. According to international management guidelines, ASB is not an indication for antibiotic treatment (with few exceptions). AIM To determine reasons for using antibiotics to treat ASB in the absence of a treatment indication. METHODS A qualitative study was conducted at a tertiary care hospital in Switzerland during 2011. We interviewed 21 internal medicine residents and attending physicians selected by purposive sampling, using a semi-structured questionnaire. Responses were analysed in an inductive thematic content approach using dedicated software (MAXQDA(®)). FINDINGS In the 21 interviews, the following thematic rationales for antibiotic overtreatment of ASB were reported (in order of reporting frequency): (i) treating laboratory findings without taking the clinical picture into account (N = 17); (ii) psychological factors such as anxiety, overcautiousness, or anticipated positive impact on patient outcomes (N = 13); (iii) external pressors such as institutional culture, peer pressure, patient expectation, and excessive workload that interferes with proper decision-making (N = 9); (iv) difficulty with interpreting clinical signs and symptoms (N = 8). CONCLUSION In this qualitative study we identified both physician-centred factors (e.g. overcautiousness) and external pressors (e.g. excessive workload) as motivators for prescribing unnecessary antibiotics. Also, we interpreted the frequently cited practice of treating asymptomatic patients based on laboratory findings alone as lack of awareness of evidence-based best practices.

Design and synthesis of constrained azacyclic pyrrolidine analogues of FTY720 as anticancer agents & metal coordination-controlled and bifunctional catalysis toward tertiary β-Ketols

Cette thèse se compose en deux parties: Première Partie: La conception et la synthèse d’analogues pyrrolidiniques, utilisés comme agents anticancéreux, dérivés du FTY720. FTY720 est actuellement commercialisé comme médicament (GilenyaTM) pour le traitement de la sclérose en plaques rémittente-récurrente. Il agit comme immunosuppresseur en raison de son effet sur les récepteurs de la sphingosine-1-phosphate. A fortes doses, FTY720 présente un effet antinéoplasique. Cependant, à de telles doses, un des effets secondaires observé est la bradycardie dû à l’activation des récepteurs S1P1 et S1P3. Ceci limite son potentiel d’utilisation lors de chimiothérapie. Nos précédentes études ont montré que des analogues pyrrolidiniques dérivés du FTY720 présentaient une activité anticancéreuse mais aucune sur les récepteurs S1P1 et S1P3. Nous avons soumis l’idée qu’une étude relation structure-activité (SARs) pourrait nous conduire à la découverte de nouveaux agents anti tumoraux. Ainsi, deux séries de composés pyrrolidiniques (O-arylmethyl substitué et C-arylmethyl substitué) ont pu être envisagés et synthétisés (Chapitre 1). Ces analogues ont montré d’excellentes activités cytotoxiques contre diverses cellules cancéreuses humaines (prostate, colon, sein, pancréas et leucémie), plus particulièrement les analogues actifs qui ne peuvent pas être phosphorylés par SphK, présentent un plus grand potentiel pour le traitement du cancer sans effet secondaire comme la bradycardie. Les études mécanistiques suggèrent que ces analogues de déclencheurs de régulation négative sur les transporteurs de nutriments induisent une crise bioénergétique en affamant les cellules cancéreuses. Afin d’approfondir nos connaissances sur les récepteurs cibles, nous avons conçu et synthétisé des sondes diazirine basées sur le marquage d’affinité aux photons (méthode PAL: Photo-Affinity Labeling) (Chapitre 2). En s’appuyant sur la méthode PAL, il est possible de récolter des informations sur les récepteurs cibles à travers l’analyse LC/MS/MS de la protéine. Ces tests sont en cours et les résultats sont prometteurs. Deuxième partie: Coordination métallique et catalyse di fonctionnelle de dérivés β-hydroxy cétones tertiaires. Les réactions de Barbier et de Grignard sont des méthodes classiques pour former des liaisons carbone-carbone, et généralement utilisées pour la préparation d’alcools secondaires et tertiaires. En vue d’améliorer la réaction de Grignard avec le 1-iodobutane dans les conditions « one-pot » de Barbier, nous avons obtenu comme produit majoritaire la β-hydroxy cétone provenant de l’auto aldolisation de la 5-hexen-2-one, plutôt que le produit attendu d’addition de l’alcool (Chapitre 3). La formation inattendue de la β-hydroxy cétone a également été observée en utilisant d’autres dérivés méthyl cétone. Étonnement dans la réaction intramoléculaire d’une tricétone, connue pour former la cétone Hajos-Parrish, le produit majoritaire est rarement la β-hydroxy cétone présentant la fonction alcool en position axiale. Intrigué par ces résultats et après l’étude systématique des conditions de réaction, nous avons développé deux nouvelles méthodes à travers la synthèse sélective et catalytique de β-hydroxy cétones spécifiques par cyclisation intramoléculaire avec des rendements élevés (Chapitre 4). La réaction peut être catalysée soit par une base adaptée et du bromure de lithium comme additif en passant par un état de transition coordonné au lithium, ou bien soit à l’aide d’un catalyseur TBD di fonctionnel, via un état de transition médiée par une coordination bidenté au TBD. Les mécanismes proposés ont été corroborés par calcul DFT. Ces réactions catalytiques ont également été appliquées à d’autres substrats comme les tricétones et les dicétones. Bien que les efforts préliminaires afin d’obtenir une enantioselectivité se sont révélés sans succès, la synthèse et la recherche de nouveaux catalyseurs chiraux sont en cours.

Diversity of benthic foraminiferal faunas in Tertiary and Quaternary sediments of DSDP Hole 33-317_Site from the Manihiki Plateau, Pacific Ocean (Table 1)

A study is made of the benthic foraminifers (size fraction > 63 µm) recovered from 59 upper Eocene through Quaternary sediment samples at DSDP Site 317 (Leg 33), located at a depth of 2598 m in the central part of the Manihiki Plateau (South Pacific). The sediments cored are disturbed in only two samples. The stratigraphic assignements used are based on previous studies of planktic foraminifers and other microfossils. In total, 216 taxa are identified. A cluster analysis based on the 77 species which comprised 5% or more of the entire foraminiferal assemblage in at least one sample suggests the presence of 3 major biostratigraphic zones corresponding approximately to the following ages, zone A: middle Miocene-Quaternary; zones B-C: early Miocene-Oligocene; and zone D: Eocene. The most important faunal turnover occurred between the Eocene and the Oligocene; a less pronounced break took place between the early and the middle Miocene, and an additional minor turnover between the Oligocene and the early Miocene. Eighteen taxa are long-ranging, being recorded from the middle Eocene through the Pliocene-Quaternary. It is concluded that, in general, benthic foraminifers of the bathyal zone are poor worldwide stratigraphic guide fossils; the following taxa are conditionally considered as the most suitable in the Eocene-Quaternary sequence: Aragonia aragonensis, Quadrimorphina profunda, Nuttallides truempyi, Abyssamina poagi, Buliminella grata, Bulimina jarvisi, B. macilenta, Turrilina alsatica, Cibicides notocenicus, C. wuellerstorfi, Pyrgo murrhina. However, most of these species are relatively rare.

(Table 1) Distribution of Cretaceous-Tertiary benthic foraminifers in ODP Hole 129-802A

Reworked shallow-water larger and deep-water calcareous benthic foraminifers were recovered from foraminiferal packstones and nannofossil chalks in Hole 802A. The autochthonous zeolitic pelagic claystone is characterized by late Campanian abyssal agglutinated foraminifers that allow correlation with the North Atlantic and the adjacent Pigafetta Basin. Assemblages of DendrophryalRhizammina in graded beds within the zeolitic claystone indicate reworking through entrainment in the flocculent E layer of turbidites, rather than recolonization following a biosiliceous event. Background sedimentation of the claystone took place below the carbonate compensation depth. The nannofossil chalk contains reworked lower bathyal to abyssal calcareous foraminifers of late Paleocene to early Miocene age. The topmost bed of the nannofossil chalk unit commences with an algal foraminiferal packstone containing Lepidocyclina sumatrensis, Heterostegina borneensis, Amphistegina hauerina, Asterigerina marshallana, and A. tentoria, which indicate that the source area was a shallow-water reef and allow the bed to be dated as early Miocene. The absence of obviously younger planktonic microfossils in the graded bed indicates that the resedimentation event was generally contemporaneous with original deposition and took place during an early Miocene global sea-level highstand. An early Miocene shallow-water assemblage is also seen in the graded beds at the base of a volcaniclastic turbidite sequence overlying the nannofossil chalks. Resedimentation of this unit was associated with volcanic activity some distance away.

Mineralogy ol late Quaternary marine sediments from the West and East Greenland shelves offshore from early Tertiary basalt outcrops

We use quantitative X-ray diffraction to determine the mineralogy of late Quaternary marine sediments from the West and East Greenland shelves offshore from early Tertiary basalt outcrops. Despite the similar basalt outcrop area (60 000-70 000 km**2), there are significant differences between East and West Greenland sediments in the fraction of minerals (e.g. pyroxene) sourced from the basalt outcrops. We demonstrate the differences in the mineralogy between East and West Greenland marine sediments on three scales: (1) modern day, (2) late Quaternary inputs and (3) detailed down-core variations in 10 cores from the two margins. On the East Greenland Shelf (EGS), late Quaternary samples have an average quartz weight per cent of 6.2 ± 2.3 versus 12.8 ± 3.9 from the West Greenland Shelf (WGS), and 12.02 ± 4.8 versus 1.9 ± 2.3 wt% for pyroxene. K-means clustering indicated only 9% of the samples did not fit a simple EGS vs. WGS dichotomy. Sediments from the EGS and WGS are also isotopically distinct, with the EGS having higher eNd (-18 to 4) than those from the WGS (eNd = -25 to -35). We attribute the striking dichotomy in sediment composition to fundamentally different long-term Quaternary styles of glaciation on the two basalt outcrops.

Tertiary echinoids of the Carrizo Creek region in the Colorado Desert.

Mode of access: Internet.

List of Quaternary and Tertiary Diatomaceae from deposits of southern Canada /

Mode of access: Internet.

Later Tertiary Leporidae of North America.

University of Kansas publications.

Carnivora from the Tertiary formations of the John Day region,

Mode of access: Internet.

Preliminary delineation and description of the regional aquifers of Tennessee--Tertiary aquifer system /

Shipping list no.: 86-1003-P.

The Tertiary insects of North America.

At head of title: United States Geological Survey of the Territories.