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Cromok is a Malaysian rock band. They are known to be the pioneers of Malaysian thrash metal music. Formed in 1987, original and current members consists of Shamsudin "Sam" Ali (vocals and bass), Khairul Anuar "Karl" Shariff (guitarist), and Tarmizi "Miji" Mokhtar (drummer). The band best known for their songs "Misty", "Another You", "I Don't Belong Here" and has released 8 studio albums to date. Fans of Cromok were dubbed as 'Cromers'.

History
Cromok was formed in April 1987 by four young students, Kharuddin Muhammad (Din), Shamsuddin Ali (Sam), Khairul Anuar Shariff (Karl) and Tarmizi Mokhtar (Miji). Din who was the senior among them, was instrumental in developing the musical and visual style of what is to be Cromok. They were studying at the University of Wollongong in New South Wales, Australia. While in Australia, to past extra time, they decided to form a thrash metal band and they frequently perform their music in small concert and gigs primarily in Sydney Metal Scene. They got positive responses and steadily gained their fans, made their name within the Australian Underground Thrash Metal scene rising the ranks along with Australian Godfather bands, the likes of Enticer, SSDC, Mortal Sin, Frozen Doberman, White Trash, Addictive and Detriment. Their single, "Misty" was their most popular song among their fans in those days.

In 1992, Sam, Karl and Miji returned to Malaysia meanwhile Din had already returned to Malaysia the previous year due to an unavoidable personal issue, causing them to loose the spot as Motorhead opening act. After Din went back to Malaysia, they employed the sessionist service of  some of their friend. The rhythm guitarist one of them is a guy named Erwin and the lead guitarist is called Oggy. After returning from Sydney, Cromok performed four concerts at Life Centre in Jalan Sultan Ismail on July 10 to 12, 1992. It become their first major shows since moved back to Malaysia. However, unfortunately and to the chagrin of many early Cromok fans, Din was never invited for the performance and eventual studio recording. This was despite his deep involvement with the Band and instrumental effort in developing the Cromok Bay Area/Nusantara Thrash Metal sound. Their first album/demo which was recorded during their studies, Image of Purity were released in 1990 and were distributed among the tape traders of Australian metal scene and later picked up by Valentine Sound Productions Sdn Bhd to be distributed in Malaysia. They receive positive responses, mostly among the teenagers, and build a huge local fan base in a short period of time. Their songs such as "Another You", "I Don't Belong Here", "Misty", "Metallurgical" and "Memories" were highly praised by their fans. However their success was limited due to limited reception of mainstream media by the Malaysian government at the time (Rock/Heavy Metal/Thrash Metal was unacceptable. Always being discriminated, and banned during late 1980s and early 1990s in Malaysia by Malaysian government and media). Instead, they keep expanding their musical growth, releasing seven more stellar albums; Forever In Time (1993), Yours Truly (1996), Mean, Meaner, Meanest (1999), What's Left? (2000), Deafening Silence (2002), Untitled (2004) and a few special edition compilation. Forever in Time was their most successful album to date, sold over 100,000 copies in Malaysia. A digitally remastered version of their debut album was reissued in 2000.

Khairuddin Muhammad, Din of founder singer-songwriter of the Thrash metal band Cromok and D'Cromok fame died on September 27, 1997, due to Malaria in Mersing, Johor. His remains were buried in Kampung Geting, Tumpat, Kelantan. He was survived by his widow and daughter. Due to some friction between Din and the three others (based on the inlay notes in D'Cromok 7 Years and 7 Days Part 1 and Part 2 albums), the band then continued as a trio. However, in 2001, Karl was seceding from Cromok because he wants to concentrate on his professional career and his family. Karl then was replaced by renowned Malaysian guitar maestro, Hillary Ang from iconic Malaysian rock band, Search.

In April 2005, Cromok performed live at the Planet Hollywood Kuala Lumpur. At the end of 2005, Hillary returned to Search, leaving Sam and Miji as the remaining members in Cromok. Sam then announced that they were going on sabbatical hiatus and all band activities were suspended. After almost five years of sabbatical hiatus from music scene, on April 8, 2012, they held a Reunion concert in Kuala Lumpur, Malaysia at KLive, consisting of three original members (Sam, Karl, and Miji with Shah Ziri from Nrocinu as rhythm guitar sessionist), which also celebrated the band's 25th anniversary. This was one of the latest concert of Cromok, after their last performance in Hard Rock Cafe, Bangkok. On August 21, 2013, Cromok performed as an opening act for Metallica LIVE concert in Malaysia.

On February 3, 2018, Cromok performed alongside XPDC at the Konsert Cromok & XPDC Live in MAEPS, Serdang. That same year, they announced that they will introduced a new concept of Malaysian thrash metal music, which known as Thrashditional, a portmanteau of 'thrash metal' and 'traditional'.

They are now still performing whenever there's demand and the latest concert was NUSAFEST2020, but due to COVID-19 pandemic, it was postponed until further notice.

Style
The band sings in English. They are also known to have at least one instrumental track in every album. Sam uses a teutonic thrash raspy vocal style, sometimes low guttural, while the band's music sounds similar to the Bay Area thrash metal with a touch of Malay/Nusantara feels. Cromok also often experiments with Malay cultural music elements and sounds, adding Malay elements to their artwork. They also known for incorporating unicorn on their album cover.

Members
Founding Members
 Kharuddin Muhammad (Din) - backing vocal, guitarist (1987–1992; died 1997)
 Muhammad Fadhil (Mat Puck) - guitar (1987)
 Che Dean (Denan) - guitar (1987)
 Nik Ramzee (Ji) - bass (1987)

Current members
Shamsudin Ali (Sam) - lead vocals, bass guitar (1987–present)
Tarmizi Mokhtar (Miji) - drums (1987–present)
Khairul Anuar Shariff (Karl) - lead/rhythm guitar (1987–2000; 2010–present)
Shah Sidious (formerly of tribute band Nrocinu)

Former members
 Hillary Ang - lead guitar (2000–2005)

Discography

Studio albums

Live albums

Compilation albums

Other albums

Concerts
Headlining
 Cromok Reunion Thrashing Kuala Lumpur (8 April 2012)
 Konsert Metal Legends Cromok & XPDC (3 February 2018)

Opening act
 Metallica LIVE in Malaysia (21 August 2013)

References

External links

Malaysian thrash metal musical groups
Musical groups established in 1987
Musical groups disestablished in 2006
Musical groups established in 2010
EMI Records artists
English-language singers from Malaysia


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UChicago-Centre National de la Recherche Scientifique (CNRS) Collaboration Funds
The Centre National de la Recherche Scientifique (CNRS) and the University of Chicago are launching a joint call for proposals to support collaborations between UChicago researchers and labs affiliated with CNRS, and to foster cooperation between PhD students on shared research interests.
This call is open to proposals from all disciplines and academic research areas. This program seeks to:
Support research teams that include Principal Investigator/PhD student pairs from both UChicago and a CNRS-affiliated lab
Fund up to three years of international travel expenses for each team, starting in 2023
Provide additional funding to support CNRS-affiliated PhD students
Proposals will be accepted through February 7, 2022. Please see below for full details on the program and instructions on how to apply.
Objectives of this Call for Proposals
This joint call is intended to:
Identify and support joint research teams between UChicago and CNRS-affiliated labs, via the creation of pairs of Principal Investigators and their PhD students
Fund up to three years of a PhD fellowship on the CNRS side of identified partnerships, starting in Autumn 2022
Involve UChicago-funded PhD-students interested in international collaboration
Fund mobility expenses for each team over a period of three years, starting in 2023
The CNRS and the University of Chicago are launching a Joint Call for Proposals between the two institutions, to develop cooperation in new promising themes. This call is open to all disciplines and academic research areas.
UChicago side: Assistant, Associate or Full Professors
CNRS' side: Researchers and professors (PU, MCF) working in a CNRS-affiliated lab, holding an accreditation to supervise PhD students (HDR)
A PI cannot submit more than one application in the framework of this call.
France: candidates to a PhD
UChicago: second-year or third-year PhD students
There must be at least one PI from University of Chicago and one PI from a CNRS affiliated lab. Those who do not already have a collaborator may consult the CNRS website (CNRS directory) or the UChicago website (students research, academic departments) to find information on the research groups and projects being carried out in either institution.
Amount of Funding
Funds will cover mobility costs for visits to France & to UChicago for the PI and the PhD student (up to 5,000€ for France-based awardees and $5,000 USD for UChicago awardees - per institution, per year). Students are expected to be financially supported by their home institution, at the equivalent level of a PhD fellowship in a specific program at their home institution.
Support period
Up to five students are expected to be funded by UChicago Principal Investigators, who will receive additional assistance from the University's Global office, and up to five students enrolled in a French university are expected to be funded by the CNRS.
Notification Date
End of March 2022
Close of Submissions Date
Proposals will be evaluated and ranked by a UChicago-CNRS scientific evaluation committee, according to the following criteria:
Scientific quality & originality of the project
Scientific merit of the teams
Synergism between the teams
The proposals must also include an outlined plan for raising external competitive funding (e.g. EU collaborative grants, national research agency grants, etc.).
The proposal must consist of the following parts.
UChicago applicants should submit this information via InfoReady;
CNRS-affiliated applicants should submit the same information (in English) in one single Word or PDF file (up to 5 pages + the Title Page, not including references and the CVs of the French and UChicago participants) via the dedicated Web site: https://www.cooperation.cnrs.fr.
PART A: Contact Information
Names of the principal investigators and their laboratories/name of thesis director in humanities and social sciences, their addresses, telephone, and e-mail. The names of the PhD students can be provided if they are already known. For CNRS-affiliated applicants, please specify on the Title Page of the application document "This application is submitted for consideration within the UChicago - CNRS Collaboration Program". CNRS-affiliated applicants will need to use the separate cover page template provided.
PART B: Description of the Project (1,000 word limit)
Title of the project, state of the art for the research area, description of the project and domains of interest, historical context of application (if applicable), quality and originality of the project, objectives, methodology, expected results and their relevance, future perspectives. Explain how the PhD fellow will be supervised and mentored, and how the collaboration will enable and enhance the project. Explain the relation between the project and the research themes of the laboratory (if applicable).
PART C: The Added-value of International Cooperation (500 word limit)
Describe the added value of the international cooperation in fulfilling the aims of the project (explain why the project cannot be carried out at a national level only). Describe the expected benefits for the French and UChicago teams. Describe the balance between the contributions of the French and UChicago teams. If any additional industrial or governmental collaborations are involved in the project, please describe their role.
PART D: Planned Activities (500 word limit)
Describe the planned activities in the framework of the project and provide a timetable. Explain how these activities will help achieve the aims of the project.
PART E: Budget (500 word limit)
Proposed budget including a breakdown of the division of funds, separated into distinct budgets for CNRS and UChicago. The budget section regarding travel should contain explicit line items for travel of the PhD student and the Principal Investigators.
PART F: Perspectives & External Funding (500 word limit)
Outline any proposed plans for raising external competitive funding (e.g. EU collaborative grants, US collaborative grants, national research agency grants, etc.)
PART G: Ethics (250 word limit)
Does the project raise ethical questions? If yes, please describe them and how they will be addressed.
PART H: Academic Quality of the Teams
Please list and upload up to ten detailed (complete) citations for publications related to the project for each team. This list does not count against the page limit. Authors from the respective laboratories must be clearly indicated in the author lists, with superscript or parenthesized letters corresponding to the respective countries, for example Dupont JP (FR), or Smith FD (US).
PART I: Curriculum Vitae of all PIs/Faculty
Please submit short (no more than two page) curriculum vitae for all PIs/faculty (from both UChicago and French insitutions) that will be involved in this project. The CVs do not count against the 6-page application limit.
Proposals will be evaluated and ranked by a UChicago-CNRS selection committee based on the scientific quality & originality of the project, scientific merit of the teams, synergy between the teams, and alignment with the strategic areas of mutual interest.
Successful recipients will be formally notified of the award and informed of funding conditions.
During or at the conclusion of the project, grant recipients may be asked to report on progress or outcomes achieved to relevant stakeholder groups.
Awardees must submit a brief, plain language report (1-page) to their respective PI/thesis director within eighteen months of the conclusion of the award cycle. This report should detail the outcomes of the collaboration and the ways in which the grant has enhanced, or will enhance, their research activities and/or leverage larger opportunities.
For any inquiry, please contact:
UChicago inquiries should be directed to fmunch@uchicago.edu
CNRS (including about the submission platform CoopIntEER functioning) inquiries should be directed to jean.theves@cnrs-dir.fr

redpajama_set_name: RedPajamaCommonCrawl


Presented by Ron Sample, Senior Healthcare Technical Engineer, Contec Inc., and Mark Wiencek, Lead Microbiologist, Contec Inc.
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*Accurate as of February 5, 2019.


text:
Q: ViewsLifeTime is null in subsites When I'm doing a search for ViewsLifeTime with Rest API for a specific page in the root site (site collection) everything is fine, like below query:
https://site.com/_api/search/query?querytext=%27Path=https://site.com/Pages/sample.aspx%27

but when changing path to a page in subsite viewsLifeTime is null
https://site.com/_api/search/query?querytext=%27Path=https://site.com/subsite/Pages/sample.aspx%27

all options Queryable, Retrievable, Sortable, Safe for Anonymous in Managed Properties for ViewsLifeTime is enabled.
Does anyone have any suggestions?

redpajama_set_name: RedPajamaStackExchange


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Churches' Lawsuit Against Governor Walz's Emergency Order Restrictions Sustained; Attorney General Ellison's Motion to Dismiss Denied
(Golden Valley, MN) Upper Midwest Law Center's (UMLC) lawsuit claims on behalf of Northland Baptist Church, Pastor John Bruski and Living Word Christian Center against Governor Walz's discriminatory restrictions on Christian worship were sustained, and Attorney General Ellison's motion to dismiss denied by Federal Court Order on March 30, 2021. These claims will go forward to trial per the Court's Order.
Northland Baptist Church, et al. v. Governor Tim Walz and Attorney General Keith Ellison was filed on May 6, 2020, and amended several times as the Governor modified and reissued his Emergency Orders several times. The plaintiff churches and Pastors assert that the Governor has imposed irrational and discriminatory restrictions on Christian assembly and religious services in these Emergency Orders, as compared to secular venues, and that those unconstitutional interferences in religious exercise and assembly should be restrained permanently by the Court. Attorney General Ellison moved to dismiss the claims, asserting that there was, in effect, a pandemic exception to the First Amendment, and UMLC opposed that motion, which was argued on September 18, 2020. Judge Wilhelmina M. Wright issued her order sustaining the Churches' claims and denying the motion to dismiss on March 30, 2021.
Judge Wright rejected the Governor and Attorney General's attempts to create a pandemic exception to the Constitution. She held that normal constitutional scrutiny applies to all of the Churches' claims. Because high levels of constitutional scrutiny apply, Judge Wright held that Northland Baptist Church, Living Word Christian Center and Pastor John Bruski's claims for violations of their free exercise rights under the First Amendment are valid claims and will go forward with the presentation of evidence to the Court.
UMLC President, Doug Seaton, stated that: "One very noteworthy feature of this decision is that it is the first time that any court has rejected Governor Walz and Attorney General Ellison's attempt to avoid the heightened scrutiny required by the Constitution. No other Minnesota plaintiff has been successful in defeating the Attorney General's motions to dismiss on these claims, even in part. This decision will help protect Minnesotans of faith and, we are confident, as the case progresses, Minnesota business owners as well, from the oppressive government action represented by the discriminatory and irrational elements of the Emergency Orders."
On the other hand, the court incorrectly decided that our business plaintiffs could not bring an equal protection claim under these circumstances, and also dismissed our property takings claims on their behalf. When this case is finally reduced to judgment on all claims, we will appeal the denial of these equal protection and takings claims to the Eighth Circuit Court of Appeals, which we believe will reinstate these claims, too. Until then, we will continue to pursue the claims of the Churches and Pastor Bruski in the District Court.
Commenting on the decision, Pastor John Bruski of Northland Baptist Church, said: "I am relieved that, finally, the federal court has validated our claims and denied the efforts of the Governor and Attorney General to prevent us from proving that these Emergency Orders are unconstitutional infringements on our rights to assemble and worship. We plan to do just that."
UMLC Senior Trial Counsel, James V. F. Dickey, added that: "All Minnesotans should be encouraged that their religious freedoms are protected by the U.S. Constitution and that there is no 'pandemic exception' to the First Amendment allowing our state officials to prevent them from assembling and worshipping free of discriminatory and irrational restrictions. Following appeal, we believe that UMLC 's business clients will also be free of these government abuses."
To learn more about Upper Midwest Law Center, click here.
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V/H/S/2 Review
Movie: V/H/S/2
Who's tracking you?
It is not even that long ago that we reviewed V/H/S, thanks to its succes the new part is already here. With only one director returning to the anthology it is up to a new team to creat a new thrilling ride. What still is a shame is that the title got renewed from S-VHS to V/H/S/2 but will this affect the movie itself?
TAPE 49 (Directed by Simon Barrett): The wraparound story here involves two private investigators searching for a missing college student. Their search leads them to an abandoned house that happens to be littered with video cassettes and a few inviting television sets. This section is the weakest part of the movie: context, and not particularly frightening or involving context.
CLINICAL TRIALS (Directed by Adam Wingard): In a smart move, the film starts off with the most inconsequential short. A young guy receives a test-phase robotic eye implant only to discover that the implant can pick up on things invisible to the human eye - like ghosts. It's a bit gimmicky, and the acting leaves a lot to be desired, but the short is fun and doesn't outstay its welcome.
A RIDE IN THE PARK (Directed by Eduardo Sanchez and Gregg Hale): Easily the most inventive segment, this one involves a mountain biker who happens to be out in the woods when a zombie epidemic begins. Attacked and zombie-fied early on, we witness the rest of the film from the POV of the guy's GoPro camera as he devours hapless people. Wisely forgoing good taste, the zombies eventually converge on a kid's birthday party. Gruesome and very funny, this one gets points for making a tired genre fresh by showing it from a zombie's perspective.
SAFE HAVEN (Directed by Gareth Huw Evans and Timo Tjahjanto): If there's one short that necessitates seeing V/H/S/2, it's this one. The longest - and by far the most terrifying - features an Indonesian TV crew being granted access to the jungle compound of a cult leader they're profiling. I don't want to reveal anything else, other than before long, all hell breaks loose. (Literally.) The pacing here is brilliant with enough buildup and unnerving atmosphere to make the final stomach-churning moments quite horrifying. Special kudos should also go to the production design. Between the eerily realistic compound sets and some outstanding special effects.
ALIEN ABDUCTION SLUMBER PARTY (Directed by Joe Eisener): A bit of a comedown after "Safe Haven" but still quite capable, the final short depicts exactly what the title suggests. Again, the pacing here works well, with the major action occurring in the final third of the segment. The young teens are believable in their mischief and terror. Plus, we witness most of the events from the perspective of a small dog. (The kids strap their camera to the dog before things turn scary.) In many ways, this short went in a direction that I wish "Signs" or "Super 8" had the guts to take.
I must say V/H/S/2 is a better than the first the tapes are less of the same stuff after another, and it feels to go a lot quicker and faster than in part 1. It covered a wide array of horror, from zombie to ghosts and even monster, but the addition of aliens was a nice touch. All in all I am really surprised with the quility of all the shorts! It is a lot better than in V/H/S. V/H/S/2, as a whole, is a thoroughly amusing one, and certainly one of the better horror films of the last year. It's an exceptional rarity, as well, seeing a sequel come out less than a year after its predecessor that is equal parts more efficient and more effective.
Everyone that knows me, knows that I am really an anti found footage person. But I must say thanks to the different styles of the tapes in this movie it really was refreshing! And I must say I almost liked all the shorts. Finally an anthology that can keep you interested and makes sure you aren't getting bored with it. It is for me more superb part of the two anthologies. Everything that V/H/S was missing is here. Good job.
Simon Barrett, Jason Eisener
Kelsy Abbott, Hannah Al Rashid, Fachry Albar


Provide day-to-day management of the Economic Policy team, which includes senior fellows, directors, research staff, and assistants.
Work with the Executive team and other senior American Progress officials to set the strategic direction for the Economic Policy team.
Develop new economic policy ideas that can shape the progressive agenda.
American Progress teams, including the Executive, Government Affairs, Communications, Development, and Administrative departments.
Play a leading role in fundraising in order to meet the Economic Policy team's commitments and allow the team to take on new projects and programs.
Represent American Progress' Economic Policy team with the public, media, and other outside groups and individuals as necessary.
Promote American Progress' economic policy priorities and work products, both inside and outside of the organization.
Assist team members in crafting and timing policy reports and rapid-response documents that are relevant to the broader economic policy debate.
Work closely with other policy teams to find areas of overlap and define shared messages and policy strategies.
Keep American Progress staff updated on news and events related to economic policy debates in Congress and the administration and respond to requests for information from executive and other senior staff.
Bachelor's degree is required. A master's or other postgraduate degree in economics, public policy, law, or another field related to economic policy is preferred.
At least 10 years of experience working in a policy organization, legislative office, or other relevant field.
Strong quantitative skills are a plus.
Fundraising experience and existing relationships with funders are a plus.
Familiarity with federal, state, and local governments.
Understanding of economics and economic policies at the international, federal, state, and local levels, or a subset of these.
Proven ability to work in a fast-paced environment, both independently and as part of a team.
Experience working with 501(c)(3) and 501(c)(4) organizations is a plus.
Strong commitment to American Progress' mission and goals.


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Ecological validity of cost-effectiveness models of universal HPV vaccination: a protocol for a systematic review
Giampiero Favato1, 2Email authorView ORCID ID profile,
Emmanouil Noikokyris2 and
Riccardo Vecchiato2
Accepted: 6 January 2017
Sexually transmitted infection with high-risk, oncogenic strains of human papillomavirus (HPV) still induces a relevant burden of diseases on both men and women. Although vaccines appear to be highly efficacious in preventing the infection of the most common high-risk strains (HPV 6, 11, 16, 18), important questions regarding the appropriate target population for prophylactic vaccination are still debated. Models in the extant literature seem to converge on the cost-effectiveness of high coverage (>80%) of a single cohort of 12-year-old girls. This vaccination strategy should provide an adequate level of indirect protection (herd immunity) to the unvaccinated boys. This argument presupposes the ecological validity of the cost-effectiveness models; the implicit condition that the characteristics of the individuals and the sexual behaviours observed in the models is generalisable to the natural behaviours of the population.
The primary aim of this review is to test the ecological validity of the cost-effectiveness models of universal HPV vaccination available in the literature. The ecological validity of each model will be defined by the number of representative characteristics and behaviours taken into consideration.
Nine bibliographic databases will be searched: MEDLINE (via PubMed); Scopus; Science Direct; EMBASE via OVID SP, Web of Science, DARE, NHIR EED and HTA (via NHIR CRD); and CINHAL Plus. An additional search for grey literature will be conducted on Google Scholar and Open Grey. A search strategy will be developed for each of the databases. Data will be extracted following a pre-determined spreadsheet and then clustered and prioritised: the main outcomes will report the inputs to the demographic and epidemiological model, while additional outcomes will refer to basic inputs to the cost-effectiveness valuation.
Each study included in the review will be scored by the number of representative characteristics and behaviours taken into consideration (yes or no) on both dimensions. Individual study's scores will be plotted in a 2 by 2 matrix: studies included in the upper right quadrant will be defined as ecologically valid, since which both individuals' characteristics and their sexual behaviours are representative.
The proposed systematic review will be the first to assess the ecological validity of cost-effectiveness studies. In the context of sexually transmitted diseases, when this condition is violated, an error in predicting the protective impact of herd immunity would occur. Hence, a vaccination policy informed on ecologically invalid models would potentially expose boys to a residual risk of contracting HPV-induced malignancies.
Genital Wart
Ecological Validity
Sexually transmitted infection with high-risk, oncogenic strains of human papillomavirus (HPV) imposes a significant economic burden on public health providers. Much of the information on HPV centres on women since having the virus increases the risk of invasive cervical cancer. But HPV virus may cause other neoplastic benign and malignant lesions, equally affecting men and women [1]. The total lifetime costs attributable to non-cervical, HPV-induced diseases were found comparable for both sexes [2].
Over the last decade, the advent of the bivalent (Cervarix, GlaxoSmithKline) and the quadrivalent (Gardasil, Merck Sharp & Dohme) vaccine in addition to screening paradigms held promise for reducing the long-term, cumulative burden of HPV-induced diseases. The trade-off was an incremental annual investment in vaccination programmes. Under the constraint of scarce public resources, policy makers relied on economic valuation to inform the decision to add the HPV vaccination to existing immunisation programmes. According to previously published reviews, most cost-effectiveness studies in the extant literature evaluated women-only direct immunisation programmes [3–5]. The few studies which included males in the valuation of HPV vaccination seemed to reach controversial conclusions [6, 7]. A recent review focused on a range of values missing from most studies, such as indirect costs, right to access treatment and health equalities [8].
The unresolved dichotomy between public health leaders who advocate the urgency of vaccinating boys against HPV [9] and policy makers who are hesitant to allocate economic resources to universal (boys and girls) vaccination calls for a methodological review of the cost-effectiveness models used to inform the decisions of the latter.
The primary aim of this review is to test the ecological validity of the cost-effectiveness models available in the literature. This can be framed by asking if the models provide an acceptable representation of the intended reality on all relevant dimensions.
This systematic review protocol will adhere to the reporting guidelines of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Protocols (PRISMA-P) statement [10]. The PRISMA-P checklist can be found in Additional file 1.
Ecological validity has typically been taken to refer to whether or not one can generalise from observed behaviour in the laboratory to natural behaviours in the world [11]. In fact, ecological validity or the related idea of external validity has a long history in psychology and economics, with the issues central to this idea frequently and continuously debated [12].
The demand for ecological validity stems from the Brunswick's concept of representative design, a construct used to assess whether an experiment or a model captures the relevant features of intended realities [13]. Using the replica model analogy [14], this can be framed by asking how well the model mimics reality on characteristics relevant to the theory. Central to representative design is the notion that any model can be thought as a sample of behaviours. For results to be generalisable, not only should attributes of participants be representative but also their expected behaviours in the specific task or situation. To do this, investigators need to specify the relevant characteristics and behaviour of the population related to the intended situation. In addition, sampling should take place on two dimensions. One involves the participants; the other concerns the situations or tasks with which the participants are confronted. Valid inferences can only be achieved by sampling in a representative manner on both dimensions.
Applied to cost-effectiveness of universal HPV vaccination, models chosen to inform public immunisation policies should take into account most of the dimensions relevant to the population (individuals susceptible to HPV infection) as well as to the specific situation (patterns of sexual mixing).
Challenges of modelling sexual behaviour
Traditionally, patterns of sexual behaviour have been characterised by focusing on the individual as unit of analysis, e.g. by measuring an individual's number of sexual partners. However, adopting a network approach to the epidemiology of sexually transmitted infections reveals that behaviours and sexual preferences may influence the spread of infection [15]. The ecological theory of infectious disease discusses the characteristics of the individuals and the patterns of the sexual mixing relevant to HPV infection [16]. Gender, age, ethnicity, sexual activity, rate of change of sexual partners and frequency of unprotected sex are characteristics representative of individuals at risk of infection [17–19]. Concurrent partnership and assortative mixing are relevant to the model's representativeness of sexual mixing. Concurrent partnerships are those in which the same individual is involved in sexual partnerships occurring simultaneously, as opposed to "serial monogamy" where one partnership ends before another one starts. The proportion of concurrent partnerships effectively increases the risk of sexually transmitted infections in the population [20, 21]. The risk of infection varies according to whether partnerships are formed between people from similar (positive assortative) or different (negative assortative) prevalence and sexual activity groups. Sex with partners of the same sex (positive) [22], sex with older partners (negative) [23], sex with a foreign partner (negative) [24] and pay for sex (negative) [25] are the four behaviours which increase the heterogeneity in the population, since some susceptible individuals are more likely to acquire and transmit the infection. If the high-risk individuals mix randomly, the infection is more likely to spread [26].
Building upon the same methodological premise of ecology of infectious disease, the Natsal survey is aimed to understand the most current characteristics of sexual partners and partnerships in the general British population. Three Natsal surveys have taken place up to day: Natsal-1 in 1990–1991, Natsal-2 in 1999–2001 and Natsal-3 in 2010–2012. In the Natsal-3 [27, 28], the following five characteristics have been identified to be representative of the participants (sexually active individuals):
Number of susceptible individuals (population size and growth)
Self-defined sexual identity
The following five behaviours have been identified as representative of situation (sexual mixing):
Sexual activity (rate of change of sexual partners)
Concurrent sexual partnerships
At least one sexual partner from outside the UK
Paid for sex
Frequency of unprotected sex
Individual characteristics and sexual mixing behaviours are relevant to the ecological validity of modelling sexually transmitted infections. For the normative outcomes of cost-effectiveness of universal HPV vaccination to be generalisable and inform public health policies, claims need to be established for the representative design of their underlying models. Ex ante, valid inferences should only be drawn by models which include all the eleven dimensions relevant to individuals and their sexual partner network. Ex post, the relative degree of representativeness of cost-effectiveness studies can be assessed by the number of relevant characteristics and behavioural patterns taken into consideration by their underlying models.
Study rationale and objectives
The aim of this review is to test the ecological validity of the cost-effectiveness models of universal HPV vaccination available in the literature.
Ecological validity refers to the relation between real-world phenomena and the investigation of these phenomena in experimental contexts or models. This can be framed by asking if the models provide an acceptable representation of the intended reality on all relevant dimensions. In the context of sexually transmitted diseases, patterns of sexual behaviour have been traditionally characterised by focusing on the individual as unit of analysis, e.g. by measuring an individual's number of sexual partners. However, adopting a network approach to the epidemiology of sexually transmitted infections reveals that behaviours and sexual preferences may influence the spread of infection.
For results to be generalisable, not only should attributes of participants be representative but also their expected behaviour in the sexual mixing.
The review seeks to answer the following research questions:
From the perspective of ecological validity, are the economic models included in the review representative of real-life sexual attitudes and lifestyles?
To what degree would an ecological bias threaten the generalisability of the outcomes?
What are the possible implications on public health policies?
The protocol is registered in the International Prospective Register of Systematic Reviews (PROSPERO) CRD42016034145, available at: http://www.crd.york.ac.uk/PROSPERO/display_record.asp?ID=CRD42016034145
The current stage of the systematic review, as defined by PROSPERO, is:
2. Piloting of the study selection process.
Inclusion criteria are as follows:
Studies reporting the incremental cost-effectiveness ratio (ICER) per quality-adjusted life year (QALY) gained of adding males to a female-only HPV vaccination
Health outcomes not limited to cervical cancer and genital warts but including additional HPV-induced diseases, such as:
Oropharyngeal cancer
Recurrent respiratory papillomatosis (RRP)
Studies will be included if HPV universal vaccination will be compared to:
Vaccination of females only
Studies reporting a full disclosure of the inputs chosen to inform the economic model
Types of economic models:
Individual models
Transmission dynamic models
Hybrid models
Health outcomes limited to the valuation of cervical cancer and genital warts
Studies not published in English language
The following bibliographic databases will be searched: MEDLINE (via PubMed); Scopus; Science Direct; EMBASE (via OVID SP); Web of Science; EconLit (via EBSCO); DARE, NHIR EED and HTA (via CRD); and CINHAL Plus. An additional search for grey literature will be conducted on Google Scholar and Open Grey. Reviews will be included to reduce the possibility of missing relevant articles.
A search strategy will be developed for each of the main databases. Additional file 2 reports details of our planned bibliographic database search strategies for MEDLINE (via PubMed); Science Direct; EMBASE (via OVID SP); Web of Science; Scopus; CRD; CINHAL Plus; EconLit (via EBSCO); Google Scholar; and Open Grey.
The PubMed "related articles" search feature will be used to reduce the risk of missing relevant articles. References of the included studies will be searched in order to identify additional relevant studies missed. A pilot of the study selection process will be conducted before initiating the systematic search of relevant articles.
Study selection
Two graduate research associates (GRAs) will independently identify through database searching, screen, assess for eligibility and include in the review the relevant studies. Opinion of one of the reviewers will be sought to arrive at a consensus in case of disagreement on a study for inclusion.
Data will be extracted and recorded independently by two additional graduate research associates (GRAs) from the studies included in the review, according to a predefined data extraction table reported in Additional file 3.
Data extracted will be clustered and prioritised: the main outcomes will report the inputs to the demographic and epidemiological model, while additional outcomes will refer to basic inputs to the cost-effectiveness valuation.
Monetary values in different currencies will be transformed in US dollars using purchasing power parities (PPPs). Subsequently, all the monetary values will be adjusted to 2015 dollar value using the US consumer price index (CPI). Corresponding authors of various studies may be contacted by email to clarify methods and results if the need arises.
Two external experts (a health economist and a clinical oncologist) will independently assess the risks and threats to validity relative to each of the studies included in the review. The critical appraisal of included economic evaluations will be carried out in two subsequent stages:
A preliminary stage, aimed to assess the risk of bias in the estimates of treatment effect (e.g. vaccine efficacy) used as data inputs in the economic evaluation. The effectiveness of the HPV vaccines currently available has been preliminarily evaluated by the randomized clinical trials which supported regulatory approval [29]. Vaccines effect and impact of immunisation programmes have been confirmed by post-licensure observational studies [30]. The choice of the appropriate tool to assess risk of bias should reflect relevant differences in the study design. Based on the premise that both randomized clinical trials and observational studies could be equally useful to inform the estimates of relative treatment effect in cost-effectiveness models, the risk of bias will be assessed by using one of the following tools:
The Cochrane Risk of Bias tool [31] for randomized clinical trials, available online at http://handbook.cochrane.org/index.htm#chapter_8/figure_8_6_c_example_of_a_risk_of_bias_summary_figure.htm
The Cochrane ROBINS-I tool (Risk Of Bias In Non-randomized Studies – of Interventions) [32] for observational studies. The ROBINS-I tool is available online at: https://sites.google.com/site/riskofbiastool/welcome/home
A main stage, aimed to identify additional risks of bias and, ultimately, to assess the validity of the included studies. The risk assessment will follow the Consolidated Health Economic Evaluation Reporting Standards (CHEERS) approach [33]. The CHEERS statement is available online at: http://www.equator-network.org/wp-content/uploads/2013/04/Revised-CHEERS-Checklist-Oct13.pdf.
In case of misalignment of views, differences will be resolved in a dedicated meeting among reviewers.
Each study included in the review will be scored by the number of representative characteristics and behaviours taken into consideration (yes or no) on both dimensions. Individual study's scores will be plotted in a 2 by 2 matrix [34] reported in Additional file 4.
The upper right quadrant represents the ideal situation, in which both individuals' characteristics and their sexual partner networks are representatives; hence, the studies are ecologically valid. In the upper left quadrant, we have models describing representative individuals but not in a representative network. In the lower left quadrant, the network is representative but the individuals are not. Finally, in the lower right quadrant, neither the individuals nor the network are representative. Only models in the upper right quadrant provide normative economic recommendations that are fully representative, hence generalisable to inform public health policies.
This protocol describes a systematic review of cost-effectiveness evaluations of universal vaccination programmes against HPV. The primary aim of this review is to test the ecological validity of these models, defined as the degree of representativeness of the individuals susceptible to infection and their sexual preferences and lifestyles.
Eventual gaps identified in this systematic review would have a significant impact on current public health policies. Models in the extant literature seem to converge on the cost-effectiveness of high coverage (>80%) of a single cohort of 12-year-old girls. This vaccination strategy should provide an adequate level of indirect protection (herd immunity) to the unvaccinated boys. This argument presupposes the ecological validity of the cost-effectiveness models; the implicit condition that the characteristics of the individuals and the sexual behaviours observed in the models is generalisable to the natural behaviours of the population. If the ecological validity condition is violated, an error in estimating the protective impact of herd immunity would occur. Hence, a vaccination policy informed on ecologically invalid models would potentially expose boys to a residual risk of contracting HPV-induced malignancies.
CHEERS:
Consolidated Health Economic Evaluation Reporting Standards
CINHAL:
CPI:
CRD:
Centre for reviews and dissemination
Database of abstracts of reviews and effects
EED:
Economic evaluation database
GRA:
Graduate research associate
HPV:
HTA:
ICER:
Incremental cost-effectiveness ratio
PPP:
Purchasing power parities
QALY:
Quality-adjusted life years
Recurrent respiratory papillomatosis
This protocol has received no funding.
The dataset supporting the conclusions of this article is included within the article and its additional files.
GF conceived this review. All authors equally contributed to the development and review of the study design. GF wrote the initial draft of this paper which was iteratively reviewed by MN and RV. All authors read and approved the final manuscript.
Additional file 1: PRISMA-P 2015 checklist. List of recommended items to address in a systematic review protocol. (DOC 82 kb)
Additional file 2: Search strategies. The data provided shows the comprehensive search strategy for the main bibliographic databases. (DOCX 15 kb)
Additional file 3: Data extraction table. The table identifies the specific information to extract for each data category chosen to inform the systematic review. (DOCX 18 kb)
Additional file 4: Data synthesis matrix. The matrix provides a graphical representation of the ecological validity of each cost-effectiveness model included in the systematic review. (PPTX 67 kb)
Institute of Leadership and Management in Health, Kingston University London, London, UK
Kingston Business School, Kingston University London, Kingston Hill, Kingston-upon-Thames, KT2 7LB London, UK
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