The Cambridge Prognostic Groups for improved prediction of disease mortality at diagnosis in primary non-metastatic prostate cancer: a validation study.

Purpose: To validate a new 5-tier prognostic classification system to better discriminate cancer specific mortality in men diagnosed with primary non-metastatic prostate cancer. Patients and Methods: We applied a recently described 5 strata model (Cambridge Prognostic Groups-CPG) in 2 international cohorts and tested prognostic performance against the current standard 3 strata classification of low, intermediate or high-risk disease. Diagnostic clinico-pathological data of men from Prostate Cancer Data Base Sweden (PCBaSe) and the Singapore Health Study were used. The main outcome measure was prostate cancer mortality (PCM) stratified by age group and treatment modality. Results: The PCBaSe cohort included 72,337 men, of whom 7,162 died of prostate cancer. The CPG model successfully classified men with different risks of PCM with competing risk-regression confirming significant intergroup distinction (p<0.0001). The CPGs were significantly better at stratified prediction of PCM compared to the current 3-tier system (C-Index 0.81 vs. 0.77, p<0.0001). This superiority was maintained for every age group division (p<0.0001). Also in the ethnically different Singapore cohort of 2,550 men with 142 prostate cancer deaths, the CPG model outperformed the 3 strata categories (C-Index 0.79 vs. 0.76, p<0.0001). The model also retained superior prognostic discrimination in treatment sub-groups - Radical prostatectomy (n=20,586): C-Index 0.77 vs. 074, radiotherapy (n=11,872): C-Index 0.73 vs. 0.68, and conservative management (n=14,950): C-Index 0.74 vs. 0.73. The CPG groups that sub-divided the old intermediate (CPG2 vs. CPG3) and high-risk categories (CPG4 vs.CPG5) significantly discriminated PCM outcomes after radical therapy or conservative management (p<0.0001). Conclusion: This validation study of nearly 75,000 men, confirms that the CPG 5-tiered prognostic model has superior discrimination in predicting prostate cancer death over the 3-tier model across different age and treatment groups. Crucially, it identifies distinct sub-groups of men within the old intermediate-risk and high-risk criteria who have very different prognostic outcomes We therefore propose adoption of the CPG model as a simple to use but more accurate prognostic stratification tool to help guide management for men with newly diagnosed prostate cancer

Disodium μ-triethylenetetraaminehexa-acetato-bis[oxovanadate(IV)] hexahydrate

The crystals structure of the title heterometallic coordination compound, Na-2[(C18H24N4O12)(VO)(2)].6H(2)O, is built of Na+ cations, binuclear [C18H24N4O12(VO)(2)](2-) dianions and water molecules. The cations and anion occupy special positions at inversion centers. The V atom has an octahedral coordination environment formed by the vanadyl oxo atom [V=O 1.618 (3) Angstrom], two N [V - N 2.174 (4) and 2.289 (4) Angstrom] and three O atoms [V - O 1.993 (3), 1.998 (3) and 2.001 (3) Angstrom] of the amino-carboxylato group

Human preferences for sexually dimorphic faces may be evolutionarily novel

This article has been made available through the Brunel Open Access Publishing Fund.A large literature proposes that preferences for exaggerated sex typicality in human faces (masculinity/femininity) reflect a long evolutionary history of sexual and social selection. This proposal implies that dimorphism was important to judgments of attractiveness and personality in ancestral environments. It is difficult to evaluate, however, because most available data come from largescale, industrialized, urban populations. Here, we report the results for 12 populations with very diverse levels of economic development. Surprisingly, preferences for exaggerated sex-specific traits are only found in the novel, highly developed environments. Similarly, perceptions that masculine males look aggressive increase strongly with development, specifically, urbanization. These data challenge the hypothesis that facial dimorphism was an important ancestral signal of heritable mate value. One possibility is that highly developed environments provide novel opportunities to discern relationships between facial traits and behavior by exposing individuals to large numbers of unfamiliar faces, revealing patterns too subtle to detect with smaller samples

Airports at Risk: The Impact of Information Sources on Security Decisions

Security decisions in high risk organizations such as airports involve obtaining ongoing and frequent information about potential threats. Utilizing questionnaire survey data from a sample of airport employees in European Airports across the continent, we analyzed how both formal and informal sources of security information affect employee's decisions to comply with the security rules and directives. This led us to trace information network flows to assess its impact on the degree employees making security decisions comply or deviate with the prescribed security rules. The results of the multivariate analysis showed that security information obtained through formal and informal networks differentially determine if employee will comply or not with the rules. Information sources emanating from the informal network tends to encourage employees to be more flexible in their security decisions while formal sources lead to be more rigid with complying with rules and protocols. These results suggest that alongside the formal administrative structure of airports, there exists a diverse and pervasiveness set of informal communications networks that are a potent factor in determining airport security levels

Towards Forward Secure Internet Traffic

Forward Secrecy (FS) is a security property in key-exchange algorithms which guarantees that a compromise in the secrecy of a long-term private-key does not compromise the secrecy of past session keys. With a growing awareness of long-term mass surveillance programs by governments and others, FS has become widely regarded as a highly desirable property. This is particularly true in the TLS protocol, which is used to secure Internet communication. In this paper, we investigate FS in pre-TLS 1.3 protocols, which do not mandate FS, but still widely used today. We conduct an empirical analysis of over 10 million TLS servers from three different datasets using a novel heuristic approach. Using a modern TLS client handshake algorithms, our results show 5.37% of top domains, 7.51% of random domains, and 26.16% of random IPs do not select FS key-exchange algorithms. Surprisingly, 39.20% of the top domains, 24.40% of the random domains, and 14.46% of the random IPs that do not select FS, do support FS. In light of this analysis, we discuss possible paths toward forward secure Internet traffic. As an improvement of the current state, we propose a new client-side mechanism that we call "Best Effort Forward Secrecy" (BEFS), and an extension of it that we call "Best Effort Forward Secrecy and Authenticated Encryption" (BESAFE), which aims to guide (force) misconfigured servers to FS using a best effort approach. Finally, within our analysis, we introduce a novel adversarial model that we call "discriminatory" adversary, which is applicable to the TLS protocol

Transformation Pathways of Silica under High Pressure

Concurrent molecular dynamics simulations and ab initio calculations show that densification of silica under pressure follows a ubiquitous two-stage mechanism. First, anions form a close-packed sub-lattice, governed by the strong repulsion between them. Next, cations redistribute onto the interstices. In cristobalite silica, the first stage is manifest by the formation of a metastable phase, which was observed experimentally a decade ago, but never indexed due to ambiguous diffraction patterns. Our simulations conclusively reveal its structure and its role in the densification of silica.Comment: 14 pages, 4 figure

Screening for inborn errors of metabolism in high-risk children: a 3-year pilot study in Zhejiang Province, China

<p>Abstract</p> <p>Background</p> <p>Tandem mass spectrometry (MS/MS) has been available in China for 8 years. This technique makes it possible to screen for a wide range of previously unscreened inborn errors of metabolism (IEM) using a single test. This 3-year pilot study investigated the screening, diagnosis, treatment and outcomes of IEM in symptomatic infants and children.</p> <p>Methods</p> <p>All children encountered in the Newborn Screening Center of Zhejiang Province during a 3-year period with symptoms suspicious for IEM were screened for metabolic diseases. Dried blood spots were collected and analyzed by tandem mass spectrometry. The diagnoses were further confirmed by clinical symptoms and biochemical analysis. Neonatal intrahepatic cholestasis caused by citrin deficiency, ornithine transcarbamylase deficiency and primary carnitine deficiency were confirmed by DNA analysis.</p> <p>Results</p> <p>A total of 11,060 symptomatic patients (6,720 boys, 4,340 girls) with a median age of 28.8 months (range: 0.04-168.2 months) were screened. Among these, 62 were diagnosed with IEM, with a detection rate of 0.56%. Thirty-five were males and 27 females and the median age was 3.55 months (range 0.07-143.9 months). Of the 62 patients, 27 (43.5%) had aminoacidemias, 26 (41.9%) had organic acidemias and nine (14.5%) had fatty acid oxidation disorders.</p> <p>Conclusions</p> <p>Because most symptomatic patients are diagnosed at an older age, mental retardation and motor delay are difficult to reverse. Additionally, poor medication compliance reduces the efficacy of treatment. More extensive newborn screening is thus imperative for ensuring early diagnosis and enhancing the treatment efficacy of IEM.</p

Diaquaiminodiacetatonickel(II)

The iminodiacetate dianion in diaquaiminodiacetato-nickel(II), [Ni(C4H5NO4)(H2O)(2)], chelates to the Ni atom through two carboxyl O and one imino N atoms; the six-fold coordination coordination environment comprises these three atoms, the water molecules and the carbonyl O atom of an adjacent dianionic group. The dative Ni<--O linkage leads to the formation of a helical chain running along the a axis of the orthorhombic crystal; adjacent chains are held in a network motif by hydrogen bonds

Disodium bis(1,2,4,5-benzenetetracarboxylato)-dihydroxytetrazincate(II) pyrazine

The tetranuclear dianion of the title compound, Na-2[Zn-4(C10H2O8)(2)(OH)(2)] . C4H4N2, forms a network framework in which the Zn atom exists in a tetrahedral environment, as it is coordinated by the carboxyl O atoms belonging to three different (C10H2O8)(4-) anions as well as by the bridging OH group. Adjacent OH groups are linked together through the uncoordinated heterocycle, which lies on a site of 2/m symmetry. The octahedrally coordinated Na ion, which lies on a site of 2 symmetry, interacts with one O atom of the carboxyl group of two anions and with two O atoms of the ortho-carboxyl groups of two other anions

1,3-di-2-pyridylthiourea monohydrate

The title compound, C11H10N4S.H2O, displays an intramoleculear N-amido...N-pyridyl hydrogen bond [2.652 (2) Angstrom] that locks the thiourea unit and one pyridyl ring into coplanarity [dihedral angle 2.7 (1)degrees]. The second pyridyl ring is also coplanar with the thiourea unit [dihedral angle 2.9 (1)degrees]. Its attached N atom interacts with the lattice water molecule to form a helical hydrogen-bonded chain that runs parallel to the b axis of the orthorhombic unit cell; adjacent chains are linked into a layer-like architecture by another hydrogen bond between the water molecule and the double-bonded S atom