text:
package org.jetbrains.plugins.groovy.codeInspection;

import com.intellij.codeInspection.LocalQuickFix;
import com.intellij.codeInspection.ProblemHighlightType;
import com.intellij.codeInspection.ProblemsHolder;
import com.intellij.codeInspection.util.InspectionMessage;
import com.intellij.openapi.util.NlsSafe;
import com.intellij.openapi.util.TextRange;
import com.intellij.openapi.util.text.StringUtil;
import com.intellij.psi.PsiElement;
import org.jetbrains.annotations.NotNull;
import org.jetbrains.annotations.Nullable;
import org.jetbrains.plugins.groovy.lang.psi.GroovyElementVisitor;
import org.jetbrains.plugins.groovy.lang.psi.api.statements.GrStatement;
import org.jetbrains.plugins.groovy.lang.psi.api.statements.GrVariable;
import org.jetbrains.plugins.groovy.lang.psi.api.statements.expressions.GrExpression;
import org.jetbrains.plugins.groovy.lang.psi.api.statements.expressions.GrMethodCall;
import org.jetbrains.plugins.groovy.lang.psi.api.statements.expressions.GrReferenceExpression;
import org.jetbrains.plugins.groovy.lang.psi.api.statements.typedef.members.GrMethod;

public abstract class BaseInspectionVisitor extends GroovyElementVisitor {
  private BaseInspection inspection = null;
  private ProblemsHolder problemsHolder = null;
  private boolean onTheFly = false;

  void initialize(BaseInspection inspection, ProblemsHolder problemsHolder, boolean onTheFly) {
    this.inspection = inspection;
    this.problemsHolder = problemsHolder;
    this.onTheFly = onTheFly;
  }

  protected void registerStatementError(GrStatement statement, Object... args) {
    final PsiElement statementToken = statement.getFirstChild();
    registerError(statementToken, args);
  }

  protected void registerError(PsiElement location) {
    if (location == null) {
      return;
    }
    final LocalQuickFix[] fix = createFixes(location);
    String description = StringUtil.notNullize(inspection.buildErrorString(location));

    registerError(location, description, fix, ProblemHighlightType.GENERIC_ERROR_OR_WARNING);
  }

  protected void registerMethodError(GrMethod method, Object... args) {
    if (method == null) {
      return;
    }
    final LocalQuickFix[] fixes = createFixes(method);
    String description = StringUtil.notNullize(inspection.buildErrorString(args));

    registerError(method.getNameIdentifierGroovy(), description, fixes, ProblemHighlightType.GENERIC_ERROR_OR_WARNING);
  }

  protected void registerRangeError(@NotNull PsiElement element, @NotNull TextRange range, Object... args) {
    String description = StringUtil.notNullize(inspection.buildErrorString(args));
    problemsHolder.registerProblem(element, range, description, createFixes(element));
  }

  protected void registerVariableError(GrVariable variable, Object... args) {
    if (variable == null) {
      return;
    }
    final LocalQuickFix[] fix = createFixes(variable);
    final String description = StringUtil.notNullize(inspection.buildErrorString(args));
    registerError(variable.getNameIdentifierGroovy(), description, fix, ProblemHighlightType.GENERIC_ERROR_OR_WARNING);
  }

  protected void registerMethodCallError(GrMethodCall method, @NlsSafe Object... args) {
    if (method == null) {
      return;
    }
    final LocalQuickFix[] fixes = createFixes(method);
    final String description = StringUtil.notNullize(inspection.buildErrorString(args));

    final GrExpression invoked = method.getInvokedExpression();
    final PsiElement nameElement = ((GrReferenceExpression)invoked).getReferenceNameElement();
    assert nameElement != null;
    registerError(nameElement, description, fixes, ProblemHighlightType.GENERIC_ERROR_OR_WARNING);
  }

  protected void registerError(@NotNull PsiElement location,
                               @InspectionMessage @NotNull String description,
                               LocalQuickFix @Nullable [] fixes,
                               ProblemHighlightType highlightType) {
    problemsHolder.registerProblem(location, description, highlightType, fixes);
  }

  protected void registerError(@NotNull PsiElement location, Object... args) {
    registerError(location, ProblemHighlightType.GENERIC_ERROR_OR_WARNING, args);
  }

  protected void registerError(@NotNull PsiElement location,
                               ProblemHighlightType highlightType,
                               Object... args) {
    final LocalQuickFix[] fix = createFixes(location);
    final String description = StringUtil.notNullize(inspection.buildErrorString(args));
    registerError(location, description, fix, highlightType);
  }

  private LocalQuickFix @Nullable [] createFixes(@NotNull PsiElement location) {
    if (!onTheFly &&
        inspection.buildQuickFixesOnlyForOnTheFlyErrors()) {
      return null;
    }
    final LocalQuickFix fix = inspection.buildFix(location);
    if (fix == null) {
      return null;
    }
    return new LocalQuickFix[]{fix};
  }

  public int getErrorCount() {
    return problemsHolder.getResultCount();
  }
}


text:
See Chris Hemsworth Looking Beat Up In Extraction 2 First Look
That's right Marvel fans — Thor isn't Chris Hemsworth's only popular action franchise. Last year the Australian actor made his debut as black ops mercenary Tyler Rake in Netflix's Extraction. Now Extraction 2 is on the way, and Hemsworth just posted a set of pictures from the set, and his character looks like he's been through the proverbial ringer.
The images come from Chris Hemsworth's official Instagram account. In the first photo, Hemsworth appears to be in character as Tyler Rake while reaching the top of a ladder leading to some kind of platform — possibly a train. As well as probably being a little chilly considering the snow in the background and falling around Rake, the hero looks like he's already seen plenty of action at this point in the story. He has at least a couple of cuts on his face and forehead, with traces of blood all over. You can see the images below.
A post shared by Chris Hemsworth (@chrishemsworth)
The second image is of Chris Hemsworth with Extraction 2 director Sam Hargrave. The pair also appeared in a brief video on Hemsworth's Instagram last week. In the clip, the Thor actor explained that they were in Prague, Czech Republic filming Extraction 2. He also mentioned that, yes, Tyler Rake is alive in spite of how things ended in the first film. How is he alive? "You're gonna have to find out," Hemsworth teased.
The snowy setting of Prague contrasts sharply from the first chapter in the film series. Extraction is set mostly in Bangladesh — with principal photography taking place in India and Thailand — where Chris Hemsworth's character is tasked with saving Ovi Mahajan (Rudhraksh Jaiswal) from kidnappers. Things go sideways after Tyler Rake gets ahold of the young Ovi, and the hero is forced to decide whether to accept a relatively easy extraction from Bangladesh while leaving the boy behind, or fighting his way through seemingly impossible odds in hopes of saving Ovi's life.
Extraction received generally positive reviews from critics, and its debut weekend on Netflix saw it shoot up to the #1 spot of all streamed content on the service. Netflix reported, per Deadline, that in the first month of its release, 90 million households streamed Extraction, giving the Chris Hemsworth action flick the biggest premiere in Netflix history at that point. It's kept that title as far as Netflix original films are concerned, but out of overall Netflix original content, Extraction was knocked out of the #1 spot this year by Squid Game.
The first Extraction was written by former Marvel Cinematic Universe architect Joe Russo, based on the 2014 graphic novel Ciudad. Russo has returned to write the sequel, and according to what he said at last year's CCXP (via Collider), we may be seeing action leads beyond Chris Hemsworth in future Extraction spin-offs. He teased the possibility of an Extrraction-based "cinematic universe," and gave the example of having David Harbour's Gaspar from the first film leading his own movie.
Whether or not we see Extraction branch out into its own series of spinoffs, Extraction 2 is expected to stream on Netflix sometime in the second half of 2022. Little is known about the story or cast, though Chris Hemsworth is returning as Tyler Rake. The sequel will be directed by Sam Hargrave from a script by Joe Russo.
First Look At Chris Hemsworth's Extraction 2 Reveals A Big Surprise
Exclusive: Chris Hemsworth Signed On For 3 More Marvel Movies
Chris Hemsworth Was Shocked Thor Wasn't In A Crucial Marvel Movie
See Chris Hemsworth Confirm Extraction 2 Filming While Covered In Snow
GTA Online Finally Has New Story Content
Olivia Wilde Trends For Wearing Sexy Two-Piece Outfits In Vogue Photoshoot
Scream 5 Trailer Reveals A New Mask For Ghostface
Steven Spielberg's New Movie Has Been Banned
NBC Just Cancelled A Fan-Favorite Series For The Second Time
See Kate Beckinsale In A Futuristic Sheer Mini-Dress
Dave Bautista Is Seeing His Dream Come True With Newly Announced Lead Role

redpajama_set_name: RedPajamaCommonCrawl


text:
package edu.hm.hafner.analysis.parser;

import java.io.StringReader;
import java.util.function.Consumer;

import org.junit.jupiter.api.Test;

import edu.hm.hafner.analysis.Report;
import edu.hm.hafner.analysis.Priority;
import static edu.hm.hafner.analysis.assertj.Assertions.*;
import edu.hm.hafner.analysis.assertj.SoftAssertions;
import static edu.hm.hafner.analysis.assertj.SoftAssertions.*;

/**
 * Tests the class {@link XlcLinkerParser}.
 */
class XlcLinkerParserTest {
    private static final String FILE_NAME = "-";

    /**
     * Parses a string with xlC linker error.
     */
    @Test
    void shouldParseLinkerError() {
        Report report = parse("ld: 0711-987 Error occurred while reading file");

        assertSingleIssue(report, softly -> {
            softly.assertThat(report.get(0))
                    .hasPriority(Priority.HIGH)
                    .hasCategory("0711-987")
                    .hasLineStart(0)
                    .hasLineEnd(0)
                    .hasMessage("Error occurred while reading file")
                    .hasFileName(FILE_NAME);
        });
    }

    /**
     * Parses a string with xlC linker error.
     */
    @Test
    void shouldParseAnotherLinkerError() {
        Report report = parse("ld: 0711-317 ERROR: Undefined symbol: nofun()");

        assertSingleIssue(report, softly -> {
            softly.assertThat(report.get(0))
                    .hasPriority(Priority.HIGH)
                    .hasCategory("0711-317")
                    .hasLineStart(0)
                    .hasLineEnd(0)
                    .hasMessage("Undefined symbol: nofun()")
                    .hasFileName(FILE_NAME);
        });
    }

    /**
     * Parses a string with xlC linker error.
     */
    @Test
    void shouldParseSevereError() {
        Report report = parse("ld: 0711-634 SEVERE ERROR: EXEC binder commands nested too deeply.");

        assertSingleIssue(report, softly -> {
            softly.assertThat(report.get(0))
                    .hasPriority(Priority.HIGH)
                    .hasCategory("0711-634")
                    .hasLineStart(0)
                    .hasLineEnd(0)
                    .hasMessage("EXEC binder commands nested too deeply.")
                    .hasFileName(FILE_NAME);
        });
    }

    /**
     * Parses a string with xlC linker warning.
     */
    @Test
    void shouldParseWarning() {
        Report report = parse("ld: 0706-012 The -9 flag is not recognized.");

        assertSingleIssue(report, softly -> {
            softly.assertThat(report.get(0))
                    .hasPriority(Priority.LOW)
                    .hasCategory("0706-012")
                    .hasLineStart(0)
                    .hasLineEnd(0)
                    .hasMessage("The -9 flag is not recognized.")
                    .hasFileName(FILE_NAME);
        });
    }

    /**
     * Parses a string with xlC linker warning.
     */
    @Test
    void shouldPareAnotherWarning() {
        Report report = parse("ld: 0711-224 WARNING: Duplicate symbol: dupe");

        assertSingleIssue(report, softly -> {
            softly.assertThat(report.get(0))
                    .hasPriority(Priority.NORMAL)
                    .hasCategory("0711-224")
                    .hasLineStart(0)
                    .hasLineEnd(0)
                    .hasMessage("Duplicate symbol: dupe")
                    .hasFileName(FILE_NAME);
        });
    }

    /**
     * Parses a string with xlC linker informational message.
     */
    @Test
    void shouldParseInformation() {
        Report report = parse("ld: 0711-345 Use the -bloadmap or -bnoquiet option to obtain more information.");

        assertSingleIssue(report, softly -> {
            softly.assertThat(report.get(0))
                    .hasPriority(Priority.LOW)
                    .hasCategory("0711-345")
                    .hasLineStart(0)
                    .hasLineEnd(0)
                    .hasMessage("Use the -bloadmap or -bnoquiet option to obtain more information.")
                    .hasFileName(FILE_NAME);
        });
    }

    private void assertSingleIssue(final Report report, final Consumer<SoftAssertions> assertion) {
        assertThat(report).hasSize(1);
        assertSoftly(assertion);
    }

    private Report parse(final String s) {
        return new XlcLinkerParser().parse(new StringReader(s));
    }
}

redpajama_set_name: RedPajamaGithub


Dubai's Roads and Transport Authority (RTA) has officially awarded the contract for the Route 2020 metro project to Expolink, a consortium of French, Spanish and Turkish companies.
The $2.9 billion (AED10.6 billion) deal covers the proposed 15km extension of the Red Line of the Dubai Metro from Nakheel Harbour & Tower Station to the site of Expo 2020, as well as the supply of 50 Alstom trains.
The contract was signed by Mattar Al Tayer, Director-General of the RTA and partners in the Expolink Consortium Henri Poupart-Lafarge, Chairman and CEO of Alstom; Jose Manuel Entrecanales, Chairman and CEO of Acciona; and Kemal Guleryuz, Chairman and CEO of Gulermack, the RTA said in a statement.
The extended line will include a 11.8km viaduct and 3.2km underground track. The project encompasses seven stations including a transfer station with the Red Line, the Expo Station, three elevated stations, and two underground stations. Acciona and Gulermack will cater to civil works, and the French Thales Group will provide the technological systems.
The test run of the newly extended line is anticipated to start in the final quarter of 2019, and the official service is scheduled for launch on 20 May 2020, five months before the opening of Expo 2020, according to Al Tayer.


text:
Linking budget analysis with aid advocacy: How civil society groups can monitor donor budget support, Sep 2007
General budget support: an alternative assistance approach (Mozambique country case study), Aug 2004
Civil society budget monitoring for national accountability, 19 Feb 2004
Report on the civil society budget forum, 2003, 27 Mar 2003
The Civil Society Organisation's role in Global Budget Support in Mozambique
Viriato Tamele
Prepared for Ownership in Practice, Informal Experts' Workshop, Paris, 27-28 September 2007
SARPN acknowledges the author as the source of this document.
[Download complete version - 51Kb < 1min (10 pages)] [ Share with a friend ]
The country
Mozambique is situated on the southeastern coast of Africa and it shares borders with Zambia, Malawi, Tanzania, Zimbabwe, Swaziland and South Africa and in the east the Indian Ocean.
The total land area of Mozambique is 801,590 sq. km.
For Administrative purposes, Mozambique is divided into 11 provinces.
Savannah and forests cover about 70 percent of the land area. By the constitution the land is owned by the state.
Mozambique has a coastline of 2,700 km in length with very rich marine resources. Mozambique is also endowed with over 100 rivers including the Zambezi, which is source for irrigation, power and other economic activities.
The population of Mozambique is estimated at 20 million. It grows at an annual rate of 7.5 percent. About 45 percent of the population comprises of young people below 15 years old. The working or active population (between ages 15 and 65) constitutes about 50 percent of the total population. About two thirds of the population lives in the coastal zone.
Mozambique is a Least Developed Countries (LDC) a United Nations category that comprises low socio-economic indicators. The economy was estimated to grow slightly faster in 2006, 7,9 percent, after the year 2005 when it expanded by 7,7 percent. Economic activity in 2006 was largely due to the recovery of agriculture sector following the return of the normal rains and re-construction. It's reported that the economy grew by 10 percent during the first half of the 2006 (Standard Bank) with a high foreign debt (originally $5.7 billion at 1998 net present value) and a notably track record on economic reform.
According to the Human Development Report of 2004 of the United Nations Development Programme (UNDP), Mozambique ranks 171st out of 177 countries on the human development index, falling below Ethiopia and only ahead of Guinea-Bissau, Burundi, Mali, Burkina Faso, Niger and Sierra Leone. The poverty remains high by all standards; some progress in poverty reduction has been achieved in recent years as a result of economic growth coupled with the Government's infrastructure development and rehabilitation programme and investment. In 2003 estimate on incidence of poverty that the percentage of total population falling below the absolute poverty line has decreased from 69 percent in 1997 to 54 percent.
Mozambique was one of the first African countries to receive debt relief under the initial Highly Indebted Poor Countries (HIPC) initiative in 1999. In April 2000, Mozambique qualified for the Enhanced HIPC as well and attained its completion point in September 2001. Mozambique, as a LDC has achieved outstanding levels of economic growth but still experiencing relatively high poverty rates. The people of Mozambique face not only the frustrating poverty rates but also significant levels of inequalities.
Aid dependency
Donors have seen Mozambique as a " success " story of peace, stability and growth since the end of its devastating war in 1992. Indeed, it has become increasingly important to the international community as one of the few so called successes were donors have invested a substantial amount of resources and effort in supporting economic and political performance.
Aid dependence in 2003, measured by total net ODA (excluding emergency aid and bilateral debt forgiveness) as a share of GNI, of 49 African countries for which data are available, was more than 10 per cent of GNI for 17 countries in 2003. Mozambique (21.8 per cent) is one of the top five aid-dependent economies including Sierra Leone and (23.3 per cent), Malawi (24.4 per cent), Guinea-Bissau (27.5 per cent) and SРіo TomР№ e Principe (51.8 per cent)
Mozambique continues to be highly aid dependent, having consistently met most donor conditions, while at the same time growing at an official average rate of about 8 percent per year since 1997. During the same period, poverty declined, but at a much slower rate. Notably Mozambique has also become a experiment by being a testing ground for so called "new aid modalities ", such as GBS, in the context of the shifting international debates around aid effectiveness, enshrined in the Paris Declaration of March 2005. This has included an innovative mechanism for monitoring donor performance on harmonisation and alignment of their support to the countries.
Global discourse on aid over the past decade, reflected in the Paris Declaration have highlighted its effectiveness and government ownership may be undermined by the way in which is delivered, with its proliferation of projects responding to donor preferences rather than government priorities, and placing too heavy a burden on an unskilled bureaucracy.
Ministers and officials spend so much time in dealing with donors and they have insufficient time left for their responsibilities. And combined with the fragmentation of the planning and budgeting system, it makes very difficult for the GoM (Government of Mozambique) side to develop alternative strategies. This is further compounded by the lack of domestic analysis and critique — intellectuals and experts who could be developing alternative and innovative thinking and approaches being brain drained.
Mozambique's aid dependence is highlighted by the fact that necessary resources cannot be easily raised domestically. Despite the emphasis that the GoM has put on increasing domestic revenues in PRSP (known as PARPA, Plano de Acзгo para a Reduзгo da Pobreza Absoluta), between 1997 and 2004 revenues fluctuated around 12 percent of GDP, without any substantial increases. Reducing aid dependence has so far proved to be an elusive goal, despite a number of reforms such as the introduction of VAT and personal income taxes. Moreover, despite much inefficiency in government spending, there are no obvious areas that could be identified for large expenditure cuts. Any reductions in spending would therefore have negative impacts on expenditures. (such as the building and repair of roads, schools, hospitals, etc., currently financed by aid in any case), or tackle the much trickier of maleficiencies, wastage and corruption. (Hanlon J & Renzio P.)
The west drivers of the current development discourse and thinking need to show to the sceptical ones that there is a stories of success even is not a success at all is one of the reasons why Mozambique is portrayed as a donor's " concubine ".
The relation between the government and the budget support partners structured by a Memorandum of Understanding, signed in 2004, which spells out the terms under which donors are willing to provide aid as GBS, the arrangements for periodic performance reviews, and the reciprocal obligations that the parties undertake to comply with.
The GoM is favourable GBS and other programmatic forms of donor support, in order to reduce aid fragmentation and increase the volume of resource, which flow through the national budget, there are series of costs and contradictions, which can be highlighted. First of all, as long different aid modalities coexist in Mozambique, the administrative burden of aid coordination is probably increasing rather than decreasing, as government officials need to devote more attention both to the large number of projects that still exist, while at the same time attending all the working group meetings created part of the GBS machinery.


text:
$(document).ready(function() {
	sample.foo();
	sample.sub.foo();
	console.log("I am only logging in source mode!");
});


text:
Browsing by Subject "RECOMMENDATIONS"
Sort by: title publication year submit date Order: ascending descending Results: 5 10 20 40 60 80 100
"Hand hygiene perception and self-reported hand hygiene compliance among emergency medical service providers : a Danish survey"
Vikke, Heidi Storm; Vittinghus, Svend; Betzer, Martin; Giebner, Matthias; Kolmos, Hans Jorn; Smith, Karen; Castren, Maaret; Lindström, Veronica; Mäkinen, Marja; Harve, Heini; Mogensen, Christian Backer (2019)
BackgroundHand hygiene (HH), a cornerstone in infection prevention and control, lacks quality in emergency medical services (EMS). HH improvement includes both individual and institutional aspects, but little is known about EMS providers' HH perception and motivations related to HH quality. Therefore, we aimed to investigate the HH perception and assess potential factors related to self-reported HH compliance among the EMS cohort.MethodsA cross-sectional, self-administered questionnaire consisting of 24 items (developed from the WHOs Perception Survey for Health-Care Workers) provided information on demographics, HH perceptions and self-reported HH compliance among EMS providers from Denmark.ResultsOverall, 457 questionnaires were answered (response rate 52%). Most respondents were advanced-care providers, males, had >5years of experience, and had received HH training
A novel CT‑based automated analysis method provides comparable results with MRI in measuring brain atrophy and white matter lesions
Kaipainen, Aku L.; Pitkänen, Johanna; Haapalinna, Fanni; Jääskeläinen, Olli; Jokinen, Hanna; Melkas, Susanna; Erkinjuntti, Timo; Vanninen, Ritva; Koivisto, Anne M.; Lötjönen, Jyrki; Koikkalainen, Juha; Herukka, Sanna-Kaisa; Julkunen, Valtteri (2021)
Purpose Automated analysis of neuroimaging data is commonly based on magnetic resonance imaging (MRI), but sometimes the availability is limited or a patient might have contradictions to MRI. Therefore, automated analyses of computed tomography (CT) images would be beneficial. Methods We developed an automated method to evaluate medial temporal lobe atrophy (MTA), global cortical atrophy (GCA), and the severity of white matter lesions (WMLs) from a CT scan and compared the results to those obtained from MRI in a cohort of 214 subjects gathered from Kuopio and Helsinki University Hospital registers from 2005 - 2016. Results The correlation coefficients of computational measures between CT and MRI were 0.9 (MTA), 0.82 (GCA), and 0.86 (Fazekas). CT-based measures were identical to MRI-based measures in 60% (MTA), 62% (GCA) and 60% (Fazekas) of cases when the measures were rounded to the nearest full grade variable. However, the difference in measures was 1 or less in 97-98% of cases. Similar results were obtained for cortical atrophy ratings, especially in the frontal and temporal lobes, when assessing the brain lobes separately. Bland-Altman plots and weighted kappa values demonstrated high agreement regarding measures based on CT and MRI. Conclusions MTA, GCA, and Fazekas grades can also be assessed reliably from a CT scan with our method. Even though the measures obtained with the different imaging modalities were not identical in a relatively extensive cohort, the differences were minor. This expands the possibility of using this automated analysis method when MRI is inaccessible or contraindicated.
Adjunctive Volasertib in Patients With Acute Myeloid Leukemia not Eligible for Standard Induction Therapy : A Randomized, Phase 3 Trial
Dohner, Hartmut; Symeonidis, Argiris; Deeren, Dries; Demeter, Judit; Sanz, Miguel A.; Anagnostopoulos, Achilles; Esteve, Jordi; Fiedler, Walter; Porkka, Kimmo; Kim, Hee-Je; Lee, Je-Hwan; Usuki, Kensuke; D'Ardia, Stefano; Won Jung, Chul; Salamero, Olga; Horst, Heinz-August; Recher, Christian; Rousselot, Philippe; Sandhu, Irwindeep; Theunissen, Koen; Thol, Felicitas; Dohner, Konstanze; Teleanu, Veronica; DeAngelo, Daniel J.; Naoe, Tomoki; Sekeres, Mikkael A.; Belsack, Valerie; Ge, Miaomiao; Taube, Tillmann; Ottmann, Oliver G. (2021)
In this phase 3 trial, older patients with acute myeloid leukemia ineligible for intensive chemotherapy were randomized 2:1 to receive the polo-like kinase inhibitor, volasertib (V; 350 mg intravenous on days 1 and 15 in 4-wk cycles), combined with low-dose cytarabine (LDAC; 20 mg subcutaneous, twice daily, days 1-10; n = 444), or LDAC plus placebo (P; n = 222). Primary endpoint was objective response rate (ORR); key secondary endpoint was overall survival (OS). Primary ORR analysis at recruitment completion included patients randomized >= 5 months beforehand; ORR was 25.2% for V+LDAC and 16.8% for P+LDAC (n = 371; odds ratio 1.66 [95% confidence interval (CI), 0.95-2.89]; P = 0.071). At final analysis (>= 574 OS events), median OS was 5.6 months for V+LDAC and 6.5 months for P+LDAC (n = 666; hazard ratio 0.97 [95% CI, 0.8-1.2]; P = 0.757). The most common adverse events (AEs) were infections/infestations (grouped term; V+LDAC, 81.3%; P+LDAC, 63.5%) and febrile neutropenia (V+LDAC, 60.4%; P+LDAC, 29.3%). Fatal AEs occurred in 31.2% with V+LDAC versus 18.0% with P+LDAC, most commonly infections/infestations (V+LDAC, 17.1%; P+LDAC, 6.3%). Lack of OS benefit with V+LDAC versus P+LDAC may reflect increased early mortality with V+LDAC from myelosuppression and infections.
An international reproducibility study validating quantitative determination of ERBB2, ESR1, PGR, and MKI67 mRNA in breast cancer using MammaTyper (R)
Varga, Zsuzsanna; Lebeau, Annette; Bu, Hong; Hartmann, Arndt; Penault-Llorca, Frederique; Guerini-Rocco, Elena; Schraml, Peter; Symmans, Fraser; Stoehr, Robert; Teng, Xiaodong; Turzynski, Andreas; von Wasielewski, Reinhard; Guertler, Claudia; Laible, Mark; Schlombs, Kornelia; Joensuu, Heikki; Keller, Thomas; Sinn, Peter; Sahin, Ugur; Bartlett, John; Viale, Giuseppe (2017)
Background: Accurate determination of the predictive markers human epidermal growth factor receptor 2 (HER2/ERBB2), estrogen receptor (ER/ESR1), progesterone receptor (PgR/PGR), and marker of proliferation Ki67 (MKI67) is indispensable for therapeutic decision making in early breast cancer. In this multicenter prospective study, we addressed the issue of inter- and intrasite reproducibility using the recently developed reverse transcription-quantitative real-time polymerase chain reaction-based MammaTyper (R) test. Methods: Ten international pathology institutions participated in this study and determined messenger RNA expression levels of ERBB2, ESR1, PGR, and MKI67 in both centrally and locally extracted RNA from formalin-fixed, paraffin-embedded breast cancer specimens with the MammaTyper (R) test. Samples were measured repeatedly on different days within the local laboratories, and reproducibility was assessed by means of variance component analysis, Fleiss' kappa statistics, and interclass correlation coefficients (ICCs). Results: Total variations in measurements of centrally and locally prepared RNA extracts were comparable; therefore, statistical analyses were performed on the complete dataset. Intersite reproducibility showed total SDs between 0.21 and 0.44 for the quantitative single-marker assessments, resulting in ICC values of 0.980-0.998, demonstrating excellent agreement of quantitative measurements. Also, the reproducibility of binary single-marker results (positive/negative), as well as the molecular subtype agreement, was almost perfect with kappa values ranging from 0.90 to 1.00. Conclusions: On the basis of these data, the MammaTyper (R) has the potential to substantially improve the current standards of breast cancer diagnostics by providing a highly precise and reproducible quantitative assessment of the established breast cancer biomarkers and molecular subtypes in a decentralized workup.
Biweekly Cabazitaxel Is a Safe Treatment Option for Metastatic Castration-resistant Prostate Cancer (mCRPC) Patients After Docetaxel - A Final Analysis of the Prosty II Trial
Kellokumpu-Lehtinen, Pirkko-Liisa; Marttila, Timo; Jekunen, Antti; Hervonen, Petteri; Klintrup, Katariina; Kataja, Vesa; Utriainen, Tapio; Luukkaa, Marjaana; Leskinen, Markku; Pulkkanen, Kalevi; Kautio, Anna-Liisa; Huttunen, Teppo (2020)
Background/Aim: Our phase III trial showed that biweekly docetaxel (D) is better tolerated than triweekly D in metastatic castration-resistant prostate cancer (mCRPC). The safety of biweekly cabazitaxel (CBZ) post-docetaxel was studied in mCRPC. Patients and Methods: Altogether, 60 patients received CBZ 16 mg/m2 i.v. on day 1 and day 14 of a 4-week cycle. The mean serum PSA levels were 305 ng/ml, and the mean age 67 years. The primary endpoint was safety according to CTCAEv4.0. Results: A total of 255 4-week cycles of CBZ were administered. The most common grade 3/4 adverse events were neutropenia (16.7%), pain (13.3%), fatigue (10.0%), anemia (5.0%) and non-neutropenic infection (10.0%). PSA responses occurred in 10 patients (16.7%). Clinical benefit rate was 38.3% and median survival 10 months. Conclusion: Biweekly CBZ is a well-tolerated treatment resulting in meaningful benefits for heavily pretreated mCRPC patients.
Bridge study protocol : an international, observational cohort study on the transition of healthcare for adolescents with chronic conditions
Kosola, Silja; Culnane, Evelyn; Loftus, Hayley; Tornivuori, Anna; Kallio, Mira; Telfer, Michelle; Miettinen, Päivi J.; Kolho, Kaija-Leena; Aalto, Kristiina; Raivio, Taneli; Sawyer, Susan (2021)
Introduction More than 10% of adolescents live with a chronic disease or disability that requires regular medical follow-up as they mature into adulthood. During the first 2 years after adolescents with chronic conditions are transferred to adult hospitals, non-adherence rates approach 70% and emergency visits and hospitalisation rates significantly increase. The purpose of the Bridge study is to prospectively examine associations of transition readiness and care experiences with transition success: young patients' health, health-related quality of life (HRQoL) and adherence to medical appointments as well as costs of care. In addition, we will track patients' growing independence and educational and employment pathways during the transition process. Methods and analysis Bridge is an international, prospective, observational cohort study. Study participants are adolescents with a chronic health condition or disability and their parents/guardians who attended the New Children's Hospital in Helsinki, Finland, or the Royal Children's Hospital (RCH) in Melbourne, Australia. Baseline assessment took place approximately 6 months prior to the transfer of care and follow-up data will be collected 1 year and 2 years after the transfer of care. Data will be collected from patients' hospital records and from questionnaires completed by the patient and their parent/guardian at each time point. The primary outcomes of this study are adherence to medical appointments, clinical health status and HRQoL and costs of care. Secondary outcome measures are educational and employment outcomes. Ethics and dissemination The Ethics Committee for Women's and Children's Health and Psychiatry at the Helsinki University Hospital (HUS/1547/2017) and the RCH Human Research Ethics Committee (38035) have approved the Bridge study protocol. Results will be published in international peer-reviewed journals and summaries will be provided to the funders of the study as well as patients and their parents/guardians.
Burden of hospitalizations and outpatient visits associated with moderate and severe acute graft-versus-host disease in Finland and Sweden : a real-world data study
Sabatelli, Lorenzo; Keränen, Mikko; Viayna, Elisabet; Roset, Montserrat; Lara, Nuria; Thunstrom, Daniel; Pfeiffer, Minja; Nicklasson, Malin; Itälä-Remes, Maija (2022)
Purpose The aim of this study was to describe patient characteristics and quantify hospital stays and outpatient visits (H&OV) following diagnosis with moderate-to-severe acute graft-versus-host disease (aGVHD) in Finland and Sweden. Methods A retrospective chart audit collected data from patient medical records of 3 specialized centers performing allogeneic hematopoietic stem cell transplantation (HSCT; Finland, n = 2; Sweden, n = 1). Eligible patients received allogeneic HSCT (January 1, 2016-June 30, 2017) from any donor source, were diagnosed with grade II-IV aGVHD (MAGIC or modified Glucksberg criteria) at any time from transplantation to 12 months before data collection, and were >= 18 years old at diagnosis. Criteria for comparing patients graded with modified Glucksberg and MAGIC severity scales were defined. Results Fifty-five patients (Finland, n = 45; Sweden, n = 10) were included. Myeloablative conditioning was the most common conditioning regimen (81.8%); immunosuppression regimens were based on combinations of methotrexate (96.4%), in vivo T-cell depletion (80.0%), cyclosporine (63.6%), mycophenolate (40.0%), and tacrolimus (34.5%). Sixteen patients (29.1%) developed grade III/IV aGVHD; skin was the most common organ involved (80.0%). Most patients required >= 1 hospital stay (89.1%; median of 2 hospitalizations per patient); 7 patients (14.3%) required admission to an intensive care unit. Median hospitalization duration from HSCT to discharge was 26 days. Most patients also required outpatient or emergency department visits (90.9%). Subgroup analyses showed longer hospital stays for patients receiving multiple treatment lines; no clear differences in H&OV were observed between prophylactic regimens. Conclusion Based on this retrospective study, moderate-to-severe aGVHD is associated with considerable healthcare resource utilization in Finland and Sweden, particularly in patients who received multiple lines of therapy.
CDX2 Loss With Microsatellite Stable Phenotype Predicts Poor Clinical Outcome in Stage II Colorectal Carcinoma
Slik, Khadija; Turkki, Riku; Carpen, Olli; Kurki, Samu; Korkeila, Eija; Sundström, Jari; Pellinen, Teijo (2019)
Current risk factors in stage II colorectal carcinoma are insufficient to guide treatment decisions. Loss of CDX2 has been shown to associate with poor clinical outcome and predict benefit for adjuvant chemotherapy in stage II and III colorectal carcinoma. The prognostic relevance of CDX2 in stage II disease has not been sufficiently validated, especially in relation to clinical risk factors, such as microsatellite instability (MSI) status, BRAF mutation status, and tumor budding. In this study, we evaluated the protein expression of CDX2 in tumor center and front areas in a tissue microarrays material of stage II colorectal carcinoma patients (n=232). CDX2 expression showed a partial or total loss in respective areas in 8.6% and 10.9% of patient cases. Patients with loss of CDX2 had shorter disease-specific survival when scored independently either in tumor center or tumor front areas (log rank P=0.012; P=0.012). Loss of CDX2 predicted survival independently of other stage II risk factors, such as MSI status and BRAF mutation status, pT class, and tumor budding (hazard ratio=5.96, 95% confidence interval=1.55-22.95; hazard ratio=3.70, 95% confidence interval=1.30-10.56). Importantly, CDX2 loss predicted inferior survival only in patients with microsatellite stable, but not with MSI-high phenotype. Interestingly, CDX2 loss associated with low E-cadherin expression, tight junction disruption, and high expression of ezrin protein. The work demonstrates that loss of CDX2 is an independent risk factor of poor disease-specific survival in stage II colorectal carcinoma. Furthermore, the study suggests that CDX2 loss is linked with epithelial-to-mesenchymal transition independently of tumor budding.
Changing activity behaviours in vocational school students : the stepwise development and optimised content of the 'let's move it' intervention
Hankonen, Nelli; Absetz, Pilvikki; Araujo-Soares, Vera (2020)
Background:School-based interventions that increase physical activity (PA) in a sustainable way are lacking. Systematic and participatory, theory and evidence-based intervention development may enhance the effectiveness of complex behavioural interventions in the long term. However, detailed descriptions of the intervention development process are rarely openly published, hindering transparency and progress in the field. Aims:To illustrate a stepwise process to develop intervention targeting PA and sedentary behaviour (SB) among older adolescents, and to describe the final, optimised version of the intervention, detailing content of sessions by theoretical determinants and techniques. Methods:Two established intervention development frameworks (Intervention Mapping and Behaviour Change Wheel) were integrated, leading to a comprehensive evidence and theory-based process. It was informed by empirical studies, literature reviews, expert and stakeholder consultation, including scenario evaluation and component pre-testing. In all steps, contextual fit and potential for sustainability were ensured by stakeholder engagement. Results:As a large majority of youth opposed decreasing screen time, increasing PA and decreasing SB were defined as target behaviours, with peers and the school context including classroom practices as key social environments in influencing youth PA (problem specification, step 1). Behavioural diagnosis (step 2) identified a variety of determinants in the domains of capability (e.g. self-regulation skills), motivation (e.g. outcome expectations) and environmental opportunities. These were organised into an intervention theory integrating several formal theories, including Self-Determination Theory. Theory-aligned principles guided material design (Step 3). Feasibility RCT allowed optimisation into a final intervention protocol (step 4). Conclusions:Intervention elements target students directly, and indirectly by changing teacher behaviour and the school and wider environment. A systematic development and optimisation led to a high potential for sustainability. The detailed intervention content, with specification of the hypothesised mechanisms, allows for other researchers to replicate, adapt or refine parts or the whole intervention, considering specific target groups and (sub-)cultures.
Chromosomal Region 11p14.1 is Associated with Pharmacokinetics and Pharmacodynamics of Bisoprolol
Fontana, Vanessa; Turner, Richard Myles; Francis, Ben; Yin, Peng; Pütz, Benno; Hiltunen, Timo P.; Ruotsalainen, Sanni; Kontula, Kimmo K.; Müller-Myhsok, Bertam; Pirmohamed, Munir (2022)
Purpose: Bisoprolol is a widely used beta-blocker in patients with cardiovascular diseases. As with other beta-blockers, there is variability in response to bisoprolol, but the underlying reasons for this have not been clearly elucidated. Our aim was to investigate genetic factors that affect bisoprolol pharmacokinetics (PK) and pharmacodynamics (PD), and potentially the clinical outcomes. Patients and Methods: Patients with non-ST elevation acute coronary syndrome were recruited prospectively on admission to hospital and followed up for up to 2 years. Patients from this cohort who were on treatment with bisoprolol, at any dose, had bisoprolol adherence data and a plasma sample, one month after discharge from index hospitalisation were included in the study. Individual bisoprolol clearance values were estimated using population pharmacokinetic modeling. Genome-wide association analysis after genotyping was undertaken using an Illumina HumanOmniExpressExome-8 v1.0 BeadChip array, while CYP2D6 copy number variations were determined by PCR techniques and phenotypes for CYP2D6 and CYP3A were inferred from the genotype. GWAS significant SNPs were analysed for heart rate response to bisoprolol in an independent cohort of hypertensive subjects. Results: Six hundred twenty-two patients on bisoprolol underwent both PK and genome wide analysis. The mean (IQR) of the estimated clearance in this population was 13.6 (10.0-18.0) L/h. Bisoprolol clearance was associated with rs11029955 (p=7.17 x10(-9)) mapped to the region of coiled-coil domain containing 34 region (CCDC34) on chromosome 11, and with rs116702638 (p=2.54 x10(-8)). Each copy of the minor allele of rs11029955 was associated with 2.2 L/h increase in clearance. In an independent cohort of hypertensive subjects, rs11029955 was associated with 24-hour heart rate response to 4-week treatment with bisoprolol (p= 9.3 x10(-5)), but not with rs116702638. Conclusion: A novel locus on the chromosomal region 11p14.1 was associated with bisoprolol clearance in a real-world cohort of patients and was validated in independent cohort with a pharmacodynamic association.
Clinical and socioeconomic impact of moderate-to-severe versus mild influenza in children
Heikkinen, T.; Silvennoinen, H.; Heinonen, S.; Vuorinen, T. (2016)
Some studies have assessed the efficacy of influenza vaccination in children separately for moderate-to-severe and any influenza, but the definition used for identifying children with moderate-to-severe illness has not been validated. We analyzed clinical and socioeconomic data from two prospective cohort studies of respiratory infections among children aged
Cohort profile : Thrombolysis in Ischemic Stroke Patients (TRISP): a multicentre research collaboration
TRISP Collaboration (2018)
Purpose The ThRombolysis in Ischemic Stroke Patients (TRISP) collaboration aims to address clinically relevant questions about safety and outcomes of intravenous thrombolysis (IVT) and endovascular thrombectomy. The findings can provide observational information on treatment of patients derived from everyday clinical practice. Participants TRISP is an open, investigator-driven collaborative research initiative of European stroke centres with expertise in treatment with revascularisation therapies and maintenance of hospital-based registries. All participating centres made a commitment to prospectively collect data on consecutive patients with stroke treated with IVT using standardised definitions of variables and outcomes, to assure accuracy and completeness of the data and to adapt their local databases to answer novel research questions. Findings to date Currently, TRISP comprises 18 centres and registers >10000IVT-treated patients. Prior TRISP projects provided evidence on the safety and functional outcome in relevant subgroups of patients who were excluded, under-represented or not specifically addressed in randomised controlled trials (ie, pre-existing disability, cervical artery dissections, stroke mimics, prior statin use), demonstrated deficits in organisation of acute stroke care (ie, IVT during non-working hours, effects of onset-to-door time on onset-to-needle time), evaluated the association between laboratory findings on outcome after IVT and served to develop risk estimation tools for prediction of haemorrhagic complications and functional outcome after IVT. Future plans Further TRISP projects to increase knowledge of the effect and safety of revascularisation therapies in acute stroke are ongoing. TRISP welcomes participation and project proposals of further centres fulfilling the outlined requirements. In the future, TRISP will be extended to include patients undergoing endovascular thrombectomy.
Combined epithelial marker analysis of tumour budding in stage II colorectal cancer
Slik, Khadija; Blom, Sami; Turkki, Riku; Välimäki, Katja; Kurki, Samu; Mustonen, Harri; Haglund, Caj; Carpén, Olli; Kallioniemi, Olli; Korkeila, Eija; Sundström, Jari; Pellinen, Teijo (2019)
Tumour budding predicts survival of stage II colorectal cancer (CRC) and has been suggested to be associated with epithelial-to-mesenchymal transition (EMT). However, the underlying molecular changes of tumour budding remain poorly understood. Here, we performed multiplex immunohistochemistry (mIHC) to phenotypically profile tumours using known EMT-associated markers: E-cadherin (adherence junctions), integrin beta 4 (ITGB4; basement membrane), ZO-1 (tight junctions), and pan-cytokeratin. A subpopulation of patients showed high ITGB4 expression in tumour buds, and this coincided with a switch of ITGB4 localisation from the basal membrane of intact epithelium to the cytoplasm of budding cells. Digital image analysis demonstrated that tumour budding with high ITGB4 expression in tissue microarray (TMA) cores correlated with tumour budding assessed from haematoxylin and eosin (H&E) whole sections and independently predicted poor disease-specific survival in two independent stage II CRC cohorts (hazard ratio [HR] = 4.50 (95% confidence interval [CI] = 1.50-13.5), n = 232; HR = 3.52 (95% CI = 1.30-9.53), n = 72). Furthermore, digitally obtained ITGB4-high bud count in random TMA cores was better associated with survival outcome than visual tumour bud count in corresponding H&E-stained samples. In summary, the mIHC-based phenotypic profiling of human tumour tissue shows strong potential for the molecular characterisation of tumour biology and for the discovery of novel prognostic biomarkers.
Compliance with the 24-h movement guidelines and the relationship with anthropometry in Finnish preschoolers : the DAGIS study
Leppänen, Marja H.; Ray, Carola; Wennman, Heini; Alexandrou, Christina; Sääksjärvi, Katri; Koivusilta, Leena; Erkkola, Maijaliisa; Roos, Eva (2019)
Background: Recent 24-h movement guidelines for the early years established recommendations for physical activity (PA), screen time (ST), and sleep. To date, few studies have focused on compliance with meeting the guidelines and their associations with health outcomes. Thus, we aimed to investigate: 1) compliance with the 24-h movement guidelines, and 2) associations between compliance and anthropometry in Finnish preschoolers. Methods: We utilized DAGIS survey data that were collected in 2015-2016 (N = 864). PA was assessed 24 h/day over 7 days using a waist-worn ActiGraph wGT3X-BT accelerometer. ST and sleep were reported by the parents during the same 7 days. Anthropometry was assessed using body mass index (BMI, kg/m(2)) and waist circumference (WC, cm). Children were classified as meeting the guidelines if they averaged >= 180 min/day of PA, which consisted of >= 60 min of moderate-to-vigorous intensity; Results: Children were physically active on average 390 (+/- 46.2) min/day and spent 86 (+/- 25.5) min/day in moderate-to-vigorous PA. They spent 76 (+/- 37.4) min/day on ST and had on average 10:21 (+/- 0:33) h:min/day of sleep. The compliance rate in meeting all three movement guidelines overall was 24%. The highest compliance rate was found for PA (85%), followed by sleep (76%) and ST (35%). Meeting guidelines separately for PA or sleep, or for both, were associated with lower WC (PA: B = -1.37, p <0.001; Sleep: B = -0.72, p = 0.009; PA + Sleep: B = -1.03, p <0.001). In addition, meeting guidelines for sleep or for both PA and sleep were associated with lower BMI (Sleep: B = -0.26, p = 0.027; PA + Sleep: B = -0.30, p = 0.007). There were no significant associations found regarding ST. Conclusions: Meeting recommendations for PA and sleep may have an important role in supporting a healthy weight status in young children. However, there is still a need to improve compliance with the 24-h movement guidelines, especially for ST.
Drugs used in incident systemic lupus erythematosus - results from the Finnish nationwide register 2000-2007
Elfving, P.; Puolakka, K.; Kautiainen, H.; Virta, L. J.; Pohjolainen, T.; Kaipiainen-Seppanen, O. (2016)
The objectives of the study were to examine the initial, first-year anti-rheumatic outpatient therapy in patients with incident SLE, as well as the concomitant use of drugs for certain comorbidities, compared to the use in the general population. The Finnish nationwide register data on special reimbursements for medication costs was screened to identify the inception cohort of 566 adult SLE patients (87% females, mean age 46.5 +/- 15.9 years) over the years 2000-2007. The patients were linked to the national Drug Purchase Register. Of those, 90% had purchased at least once some disease-modifying anti-rheumatic drugs (DMARDs) during the first year. Hydroxychloroquine was the most common (76%), followed by azathioprine (15%) and methotrexate (13%). With the exception of increase in mycophenolate mofetil, the proportions remained stable over the whole study period 2000-2007. Drugs for cardiovascular diseases, dyslipidemia, diabetes mellitus, hypothyroidism and obstructive pulmonary disease were more frequently purchased than in the sex- and age-adjusted population, with rate ratios ranging from 1.6 to 7.8. Over the years 2000-2007, almost all the patients with incident SLE in Finland started with a DMARD. Higher percentages of SLE patients were on medication for several common chronic diseases than in the population as a whole.
Early BCR-ABL1 Transcript Decline after 1 Month of Tyrosine Kinase Inhibitor Therapy as an Indicator for Treatment Response in Chronic Myeloid Leukemia
El Missiry, Mohamed; Hjorth-Hansen, Henrik; Richter, Johan; Olson-Stromberg, Ulla; Stenke, Leif; Porkka, Kimmo; Kreutzman, Anna; Mustjoki, Satu (2017)
In chronic myeloid leukemia (CML), early treatment prediction is important to identify patients with inferior overall outcomes. We examined the feasibility of using reductions in BCR-ABL1 transcript levels after 1 month of tyrosine kinase inhibitor (TKI) treatment to predict therapy response. Fifty-two first-line TKI-treated CML patients were included (imatinib n = 26, dasatinib n = 21, nilotinib n = 5), and BCR-ABL1 transcript levels were measured at diagnosis (dg) and 1, 3, 6, 12, 18, 24, and 36 months. The fold change of the BCR-ABL1 transcripts at 1 month compared to initial BCR-ABL1 transcript levels was used to indicate early therapy response. In our cohort, 21% of patients had no decrease in BCR-ABL1 transcript levels after 1 month and were classified as poor responders. Surprisingly, these patients had lower BCR-ABL1 transcript levels at dg compared to responders (31% vs. 48%, p = 0.0083). Poor responders also significantly more often had enlarged spleen (55% vs. 15%; p<0.01) and a higher percentage of Ph+ CD34+CD38- cells in the bone marrow (91% vs. 75%, p<0.05). The major molecular response rates were inferior in the poor responders (at 12m 18% vs. 64%, p<0.01; 18m 27% vs. 75%, p<0.01; 24m 55% vs. 87%, p<0.01). In conclusion, early treatment response analysis defines a biologically distinct patient subgroup with inferior long-term outcomes.
Editor's Choice - Carotid Stenosis Treatment : Variation in International Practice Patterns
Venermo, M.; Wang, G.; Sedrakyan, A.; Mao, J.; Eldrup, N.; DeMartino, R.; Mani, K.; Altreuther, M.; Beiles, B.; Menyhei, G.; Danielsson, G.; Thomson, I.; Heller, G.; Setacci, C.; Bjorck, M.; Cronenwett, J. (2017)
Objectives: The aim was to determine current practice for the treatment of carotid stenosis among 12 countries participating in the International Consortium of Vascular Registries (ICVR). Methods: Data from the United States Vascular Quality Initiative (VQI) and the Vascunet registry collaboration (including 10 registries in Europe and Australasia) were used. Variation in treatment modality of asymptomatic versus symptomatic patients was analysed between countries and among centres within each country. Results: Among 58,607 procedures, octogenarians represented 18% of all patients, ranging from 8% (Hungary) to 22% (New Zealand and Australia). Women represented 36%, ranging from 29% (Switzerland) to 40% (USA). The proportion of carotid artery stenting (CAS) among asymptomatic patients ranged from 0% (Finland) to 26% (Sweden) and among symptomatic patients from 0% (Denmark) to 19% (USA). Variation among centres within countries for CAS was highest in the United States and Australia (from 0% to 80%). The overall proportion of asymptomatic patients was 48%, but varied from 0% (Denmark) to 73% (Italy). There was also substantial centre level variation within each country in the proportion of asymptomatic patients, most pronounced in Australia (0-72%), Hungary (5-55%), and the United States (0-100%). Countries with fee for service reimbursement had higher rates of treatment in asymptomatic patients than countries with population based reimbursement (OR 5.8, 95% CI 4.4-7.7). Conclusions: Despite evidence about treatment options for carotid artery disease, the proportion of asymptomatic patients, treatment modality, and the proportion of women and octogenarians vary considerably among and within countries. There was a significant association of treating more asymptomatic patients in countries with fee for service reimbursement. The findings reflect the inconsistency of the existing guidelines and a need for cooperation among guideline committees all over the world. (C) 2017 European Society for Vascular Surgery. Published by Elsevier Ltd. All rights reserved.
Elevated serum YKL-40, IL-6, CRP, CEA, and CA19-9 combined as a prognostic biomarker panel after resection of colorectal liver metastases
Peltonen, Reetta; Gramkow, Mathias H.; Dehlendorff, Christian; Osterlund, Pia J.; Johansen, Julia S.; Isoniemi, Helena (2020)
Background The inflammatory biomarkers, YKL-40 and interleukin-6 (IL-6), are elevated in patients with metastatic colorectal cancer. We examined their associations with relapse-free survival and overall survival in combination with serum C-reactive protein (CRP), carcinoembryonic antigen (CEA), and carbohydrate antigen 19–9 (CA19-9) in patients with colorectal liver metastases. Methods Altogether 441 consecutive patients undergoing liver resection at Helsinki University Hospital between 1998 and 2013 were included in the study. Pre- and postoperative YKL-40 and IL-6 were determined from serum samples with commercially available enzyme-linked immunosorbent assay (ELISA) kits, and CRP, CEA, and CA19-9 by routine methods. Associations between these biomarkers and relapse-free and overall survival were examined using Cox regression analysis. Results Patients with 2–5 elevated biomarkers were at an increased risk of relapse compared to those with 0–1 elevated biomarkers, preoperatively (HR 1.37, 95% CI 1.1–1.72) or postoperatively (HR 1.54, 95% CI 1.23–1.92). Patients with 2–5 elevated biomarkers were also at an increased risk of death compared to those with 0–1 elevated biomarkers, preoperatively (HR 1.76, 95% CI 1.39–2.24) or postoperatively (HR 1.83, 95% CI 1.44–2.33). Conclusion The results suggest that a protein panel of the inflammatory biomarkers YKL-40, IL-6, and CRP, and the cancer biomarkers CEA and CA19-9 might identify patients that benefit from more aggressive treatment and surveillance, although the additional value of IL-6 and CRP in this aspect is limited.
Expanding the medical physicist curricular and professional programme to include Artificial Intelligence
Zanca, F.; Hernandez-Giron, I.; Avanzo, M.; Guidi, G.; Crijns, W.; Diaz, O.; Kagadis, G. C.; Rampado, O.; Lonne, P.; Ken, S.; Colgan, N.; Zaidi, H.; Zakaria, G. A.; Kortesniemi, M. (2021)
Purpose: To provide a guideline curriculum related to Artificial Intelligence (AI), for the education and training of European Medical Physicists (MPs). Materials and methods: The proposed curriculum consists of two levels: Basic (introducing MPs to the pillars of knowledge, development and applications of AI, in the context of medical imaging and radiation therapy) and Advanced. Both are common to the subspecialties (diagnostic and interventional radiology, nuclear medicine, and radiation oncology). The learning outcomes of the training are presented as knowledge, skills and competences (KSC approach). Results: For the Basic section, KSCs were stratified in four subsections: (1) Medical imaging analysis and AI Basics; (2) Implementation of AI applications in clinical practice; (3) Big data and enterprise imaging, and (4) Quality, Regulatory and Ethical Issues of AI processes. For the Advanced section instead, a common block was proposed to be further elaborated by each subspecialty core curriculum. The learning outcomes were also translated into a syllabus of a more traditional format, including practical applications. Conclusions: This AI curriculum is the first attempt to create a guideline expanding the current educational framework for Medical Physicists in Europe. It should be considered as a document to top the sub-specialties' curriculums and adapted by national training and regulatory bodies. The proposed educational program can be implemented via the European School of Medical Physics Expert (ESMPE) course modules and - to some extent - also by the national competent EFOMP organizations, to reach widely the medical physicist community in Europe.
EXPLORE: A Prospective, Multinational, Natural History Study of Patients with Acute Hepatic Porphyria with Recurrent Attacks
Gouya, Laurent; Ventura, Paolo; Balwani, Manisha; Bissell, D. Montgomery; Rees, David C.; Stölzel, Ulrich; Phillips, John D.; Kauppinen, Raili; Langendonk, Janneke G.; Desnick, Robert J.; Deybach, Jean-Charles; Bonkovsky, Herbert L.; Parker, Charles; Naik, Hetanshi; Badminton, Michael; Stein, Penelope E.; Minder, Elisabeth; Windyga, Jerzy; Bruha, Radan; Cappellini, Maria Domenica; Sardh, Eliane; Harper, Pauline; Sandberg, Sverre; Aarsand, Aasne K.; Andersen, Janice; Alegre, Félix; Ivanova, Aneta; Talbi, Neila; Chan, Amy; Querbes, William; Ko, John; Penz, Craig; Liu, Shangbin; Lin, Tim; Simon, Amy; Anderson, Karl E. (2020)
Abstract Acute hepatic porphyria comprises a group of rare, genetic diseases caused by mutations in genes involved in heme biosynthesis. Patients can experience acute neurovisceral attacks, debilitating chronic symptoms, and long-term complications. There is a lack of multinational, prospective data characterizing the disease and current treatment practices in severely affected patients. EXPLORE is a prospective, multinational, natural history study characterizing disease activity and clinical management in patients with acute hepatic porphyria who experience recurrent attacks. Eligible patients had a confirmed acute hepatic porphyria diagnosis and had experienced ≥3 attacks in the prior 12 months or were receiving prophylactic treatment. A total of 112 patients were enrolled and followed for at least 6 months. In the 12 months prior to the study, patients reported a median (range) of 6 (0-52) acute attacks, with 52 (46%) patients receiving hemin prophylaxis. Chronic symptoms were reported by 73 (65%) patients, with 52 (46%) patients experiencing these daily. During the study, 98 (88%) patients experienced a total of 483 attacks, 77% of which required treatment at a healthcare facility and/or hemin administration (median [range] annualized attack rate 2.0 [0.0-37.0]). Elevated levels of hepatic δ-aminolevulinic acid synthase 1 messenger ribonucleic acid levels, δ-aminolevulinic acid, and porphobilinogen compared with the upper limit of normal in healthy individuals were observed at baseline and increased further during attacks. Patients had impaired quality of life and increased healthcare utilization. Conclusions: Patients experienced attacks often requiring treatment in a healthcare facility and/or with hemin, as well as chronic symptoms that adversely influence day-to-day functioning. In this patient group, the high disease burden and diminished quality of life highlight the need for novel therapies. This article is protected by copyright. All rights reserved.


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A Vision for the Greenest Homes Ever
This year's New American Home, an annual concept build at the International Builders' Show in Las Vegas, reflects the most technologically advanced methods of achieving energy efficiency.
by Buck Wargo
It's not new-fangled gadgetry that makes the New American Home, a model reflecting the latest in construction and design standards, so cutting-edge. The 6,428-square-foot, five-bedroom property, which was unveiled at January's International Builders' Show in Las Vegas, doesn't spare technology—check out the "transitional" outdoor entertainment space with a custom fireplace and "vanishing edge" pool. But it's the multitude of ways the home slashes energy costs that's most noteworthy.
Located in Henderson, Nev., overlooking the Las Vegas skyline, the home was constructed using the industry's most advanced building products and techniques to optimize energy efficiency, according to the National Association of Home Builders. The property is expected to achieve LEED Emerald-level status—the National Green Building Standard's highest efficiency rating.
The home features spray-foam insulation, high-quality solar panels, automated LED lighting and green appliances, and the most energy-efficient doors and windows, according to Drew Smith, a Florida energy and green building consultant who worked on the project. While the average new home has a HERS rating of 100, the New American Home scored –16. "That's tied for the lowest for a New American Home," Smith says. "Solar made a difference. Without it, [the home's HERS rating] was 49. And for a house that large, that's the lowest HERS index we have ever seen. The calculated energy savings is about $4,000 a year because of the solar and total design of the home."
The building standards of the project reflect how home builders across the country are prioritizing high-performance construction practices, NAHB officials say. A new study from the association shows that 91% of builders are incorporating energy-efficient practices—including tight building envelopes and high-performance ventilation systems—and 69% do so on a majority of their projects. "These findings complement the results of a recent study where home buyers ranked high-performance products and practices among the top features they want in a home," says John Barrows, chair of the NAHB's Sustainability and Green Building Subcommittee. "This shows us that the value of home performance is increasing among builders and consumers."
But while builders credit consumer demand for prompting increased eco-friendly construction, they say even higher demand is necessary to influence more meaningful growth in the green-home market. Only a third of builders—still an impressive number—identify as green, according to Donna Laquidara-Carr, industry insights research director at Dodge Data & Analytics, which conducted the NAHB study.
A majority of builders and remodelers say their customers perceive green homes to be more expensive than traditional homes, Laquidara-Carr says. Still, about 70% of single-family home builders believe their customers will pay more for a green home, she adds.
Other Emerging Building Trends
The NAHB released a separate study naming the home trends, buyer preferences, and must-have features for 2020, including energy efficiency. Efficient lighting, programmable thermostats, and Energy Star–rated appliances are the green features most likely to be included in new homes this year, according to Rose Quint, the NAHB's assistant vice president of survey research.
Additionally, the study shows that the average home size continues to decrease after peaking at 2,689 square feet in 2015. It has fallen four years in a row to its current 2,520 square feet and is at its smallest since 2011. The majority of both first-time and repeat buyers say they would rather have a smaller home with high-quality amenities than a bigger home with fewer features, Quint says. The percentage of homes incorporating four or more bedrooms, three-plus bathrooms, and garages for three or more cars has also dropped to levels not seen since 2012, she adds. "This points to an industry trying to meet the demands of the entry-level home buyer. Builders are struggling to meet these demands because of factors such as restrictive zoning regulations and lot prices, with the price of a new lot in 2019 averaging $57,000."
The NAHB also highlighted home design trends coming in the future, including:
Colorful kitchens incorporating aqua, dark woods, and new, colored textures.
Crisp colors paired with warm woods.
Expansive, large-format windows.
High-quality signature front entries and improved streetscapes.
Nontraditional storage solutions. Instead of cabinetry, designers are opting for shelving, both as a storage solution and a design element.
Seamless indoor and outdoor connections.
Increased use of mixed metals, materials, and textures, including wallpaper, to add depth to designs.
Wood detailing to create texture.
Prefab Technology Evolves
Japan's largest home builder, Sekisui House, and its American subsidiary, Woodside Homes, used the backdrop of January's Consumer Electronics Show in Las Vegas to unveil its prefabricated homebuilding technology, which can speed up construction, address a shortage of skilled labor, and build homes more resilient to natural disasters.
The companies provided tours of a multimillion-dollar concept home in a luxury Vegas enclave as part of the unveiling. The companies' leaders say the two-story, 7,200-square-foot home, with four bedrooms and five-and-a-half baths, showcases design and construction systems and techniques that are unlike any the U.S. homebuilding industry has ever used.
The model home was built using a technique called Shawood, in which lumber, with the aid of computers and automation, is precision-engineered, cut, and drilled in a factory near Tokyo and shipped to the U.S. The pieces were put together in the field using number sequences on a blueprint as a guide. It's a holistic system that has been used in Japan for more than two decades, covering the home's framing, foundation, and flooring, the companies' officials say. That enables a simpler, faster, and more precise building process, including fire-resistant porcelain siding that also helps protects the home from earthquakes, hurricanes, and other natural disasters, says Joel Abney, vice president of operations at Woodside Homes.
"The goal is to showcase how the trends are changing in housing and what the future can look like," Abney says. "There hasn't been much technological advancement overall in single-family home construction because we're building the same way in the U.S. as we were 20, 50, and 100 years ago. This is looking at advancing it to that next level. The home provides U.S. companies with a template for how to build houses that are significantly more resistant to Mother Nature's forces than the traditional American stick-frame structure."
Buck Wargo is a real estate reporter and writer based in Las Vegas.
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5,887 individuals and households have been approved for nearly $13.3 million in federal grants.
Nearly $46.4 million in U.S. Small Business Administration low-interest disaster loans have been approved for 1,088 homeowners and renters and 62 businesses.
More than $6.9 million has been approved for basic housing repairs for more than 1,960 homeowners.
7,869 home inspections have been issued with 99.8 percent completed.
Approximately 2,265 survivors have not provided FEMA with the necessary information from their insurance settlements to complete their disaster assistance registration.
2,268 homeowners and renters have been approved for rental assistance.
29 survivor households are checked into hotels through the Transitional Sheltering Assistance program.
Nearly 4.3 million cubic yards of debris has been removed in Jackson County.
The disaster recovery center for Jackson County at the University Extension Office in Marianna opened Oct. 23 and has assisted more than 6,989 visitors.


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Home Uncategorized Wayne Shorter receives the 2017 Polar Music Prize
Wayne Shorter receives the 2017 Polar Music Prize
Wayne Shorter, the globally revered saxophonist, composer and ICAP co-president received the 2017 Polar Music Prize from His Majesty King Carl XVI Gustaf of Sweden at a gala ceremony at the Stockholm Concert Hall on June 15th.
The Polar Music Prize which has been called the "Nobel Prize of Music" is a Swedish international award founded in 1989 by Stig Anderson, best known as the manager of the Swedish band ABBA, with a donation to the Royal Swedish Academy of Music. Without any restrictions or nationality, the prize is to be "awarded for significant achievements in music and/or music activity, or for achievements which are found to be of great potential importance for music or musical activity, and it shall be referable to all fields within or closely connected with music".
Esperanza Spaulding, four Grammy Awards winner made an introduction about Wayne Shorter's achievements:
"Your Majesty, Your Royal Highnesses, Excellencies, ladies and gentlemen! This is such a great privilege and a joy to be here celebrating Wayne. We call him Wayne. Earlier this week we were speaking about gravity as a fundamental force in the universe and dark matter, another mysterious force that apparently works in opposition of gravity.
So if there wasn't dark matter, nothing in this whole universe be possible if it weren't for that mysterious void, a phenomenon that we don't fully understand nothing we know could exist.
And I propose there might be a third fundamental element called light matter and I think perhaps light matter is the creative force that emerges from all that's known and reaches towards the unknown binding them together and I feel like Wayne, you are the agent of light matter in this world." completed Esperanza's prolific introduction.
"And this is all about Wayne, but I would like to be a personal witness to the phenomenon of Wayne's life — expanding hearts, mind, families, communities, genres, musicians. This human being before us and lives with us this evening is such a phenomenally special being, agent of light matter, agent of change and expansion and it's such a privilege to introduce you Wayne Shorter."
Esperanza continued with the "official" portion of her introduction, "The 2017 Polar Music Prize is awarded to musician and composer Wayne Shorter from Newark New Jersey. For Wayne Shorter, music is a means of learning more about all aspects of life and the universe. He has himself aptly described his work as "drilling for wisdom". With his soprano and tenor saxophones he is an explorer. Over the course of an extraordinary career, he has constantly sought out untraveled paths.
Wayne Shorter has worked in epoch-making groups such as Art Blakey's Jazz Messengers, Miles Davis's Second Great Quintet and Weather Report. He has played on many key albums with Joni Mitchell. As a solo artist he has been making albums for six decades, and he has written a number of the most enduring compositions in the history of not only jazz, but also music and writing for symphonies around the world, again functioning as that light matter that can combine that unknown of improvisation with the structure of classical composition.
Without the musical explorations of Wayne Shorter, modern music would not have drilled so deep. Please come up on stage Wayne to receive a prize from the hands of his Majesty the King."
Then, His Majesty King Carl XVI Gustaf of Sweden welcomed and bestowed the 2017 Polar Music Prize to Wayne Shorter.
After receiving the prestigious award, Wayne Shorter gave the following remarks.
"Your majesty, Your Royal Highnesses, Excellencies, ladies and gentlemen! It is with much humility and confessing that I was completely unguarded when informed that I would be a recipient of this prestigious award.
"My appreciation for the knowledge of your country, your country's contribution to humanity awakened when I was quite young while watching the films of Ingmar Bergman and artistry of your great actors and actresses I realized how freely your country opened its heart to the world and before the phrase 'Artists and Doctors Without Borders' came into being. Sweden has a profound history of embracing and ever-seeking spirit which leaves the challenge to open all pathways to engage in the noble endeavor of creating peace and indestructible happiness in this world. Thank you again."
Wayne Shorter commented earlier:
"I am deeply honored to be awarded the 2017 Polar Music Prize and I'm looking forward to accepting it in Sweden, a country that has produced some great musicians and composers who have inspired the world. It's another great adventure for me, during a life where I've always chosen the trail less travelled because it always takes you to more interesting discoveries."
The Polar Music Prize, now in its 26 year, is considered the most prestigious accolade in music, recognizing two Laureates from different music genres. Such is the honor that artists feel when being awarded the prize that even Bob Dylan, the 2000 Laureate, attended the ceremony to receive his prize from the King. The List of Polar Music Prize Laureates reads like the ultimate musicians hall of fame, which is what Stig Anderson, its founder, intended. They include: Paul McCartney, Dizzy Gillespie, Ray Charles, Burt Bacharach, Joni Mitchell, Elton John, Bruce Springsteen, Stevie Wonder, Cecilia Bartoli, Youssou N'Dour, B.B. King, Mstislav Rostropovich and Renée Fleming.
Kay Yoshikawa


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New poll reveals how little we know about dying
Caroline Allen
Research revealed that six in 10 of us feel we know very little about the final hours or life. [Photo: Getty]
Death is one of the few inevitabilities of life.
Yet, new research suggests that six in 10 British people know little or nothing about the final hours of their lives.
Many of us learn about death through speaking to family and friends of watching TV, rather than from doctors or nurses.
This sparked the researchers to launch a campaign aimed at making death a more acceptable topic of conversation.
READ MORE: What makes us scared of dying?
The Academy of Medical Sciences interviewed almost 1000 people face to face about the topic.
One third of them refused to answer the questions about death, proving that it's a difficult subject for many.
Other countries have a more free-spirited attitude towards death with countries including Mexico, Thailand and China hosting day of the dead celebrations each year.
Now, Prof Dame Lesley Fallowfield, a cancer psychologist at the University of Sussex, wants to encourage us to speak about death more openly.
She suggests we consider creating a "death plan" in the way that many expectant parents create a birthing plan.
READ MORE: The "ultra-processed" foods which could take years off your life
She said: "We all know that events sometimes supersede your wishes, but we can think it through and make it the best it can possibly be. Making a death plan shouldn't be seen as a macabre thing to do."
As a result of our refusal to speak about death, many people do not spend the final weeks of their lives how they would have chosen.
To encourage the conversation, the academy has opened a pop-up called The Departure Lounge in Lewisham shopping centre in south-east London.
The pop-up aims to engage with people on the topic on death, with messages and questions written on suitcases all around the shop.
READ MORE: Male model dies after collapsing on runway
People have taken to Twitter to describe the installation as a "great idea" to encourage conversation.
Different versions of the lounge will be popping up across the UK this summer.


Last weekend I got quite a few Foxes cut, so yesterday I sat down and sewed them up! I'm really liking the colours I chose and am looking forward to getting more sewing done on this project! It was a dull gray rainy Saturday yesterday so the Pater and I went to a movie - Florence Foster Jenkins. What a HOOT. Meryl Streep wonderfully sings off key - not an easy thing to do, Hugh Grant is so convincing as the overly charming husband, and Simon Helberg - of Big Bang fame - was absolutely hilarious!! If you need a feel good movie and a good laugh take in this flick!
I also got more stitching done on my Wild Flowers wall hanging and am starting to think I may just may make the quilt show deadline!
Posted by Idle hands, empty brain ... at 9:17 a.m.