Monthly Archives: December 2016

Funding information Funding for this project was provided in part

Funding information
Funding for this project was provided in part by National Institutes of Health Grant Nos. U19AI107792 and R01AI107159 (S.C.). J.W.W. was supported by an NIH Ruth Kirschstein Postdoctoral Fellowship F32GM109661.
AcknowledgementsWe thank members of the Crosson lab for helpful discussions, Dr. Lauriane Quenee and Dr. Lois Zitzow for help with animal experiments, the University of Chicago Integrated Light Microscopy Core Facility, and Heather Marlatt at Nationwide Histology.
Oncolytic virus; Vaccinia virus; Submicron-sized particles; Extracellular vesicles; Microparticles; Flow cytometry; Flow virometry; Viral sorting; Quality control; Vaccine
1. Introduction
Viruses are best known as harmful pathogens that cause disease. However, some viruses are uniquely capable of promoting anti-tumor activity and cancer remission, these are called oncolytic viruses (OVs). Cancer gaba antagonist commonly display defects in interferon signaling which is a critical mechanism for antiviral defense. OVs exploit this deficiency to infect and destroy cancer cells specifically [1] and [2]. Vaccinia virus (VV) is an enveloped double-stranded DNA virus of the poxviridae family that is best known as the active ingredient in the smallpox vaccine used for global eradication of the disease. The potential of VV as an OV was revealed by showing that it displayed a natural tropism for a broad range of tumors when injected in experimental animals [3], [4], [5], [6] and [7]. Further engineering of VV to increase safety and tumor-specificity was achieved by removing its genes coding for thymidine kinase (TK, J2R) and Vaccinia growth factor (VGF, C11R). The resulting double-deleted VV (VVDD) is unable to replicate in healthy cells or induce the proliferation of nearby cells [4]. Replication of VV in cancer cells leads to tumor regression, tumor antigen exposure, and stimulation of host anti-tumor immunity, thereby positioning it as a promising anti-cancer biotherapeutic agent [2], [8] and [9]. The US Food and Drug Administration has recently approved the first OV treatment for melanoma, with an increasing number of OVs in clinical development [10] and [11].
In contrast to some viruses that are released from infected cells in large quantities, the infectious pool of VV particles exists primarily as intracellular mature virions (IMVs), also sometimes referred to as mature virions (MVs) [12] and [13]. However, small amounts of VV particles also bud from infected cells as cell-associated enveloped viruses (CEV) and extracellular enveloped viruses (EEVs) [14] and [15]. To prepare VV stocks, IMVs are harvested by lysing infected cells and then purifying the virus by density gradient centrifugation or tangential flow filtration [16] and [17]. Lysis of infected cells releases large amounts of cellular debris and molecules that may bind and co-purify with the virus if not properly eliminated. Additionally, it has long been established that VV self-aggregates, thereby altering the biophysical properties of the virus during the purification process [18] and [19]. As such, a reliable, accurate and rapid method to assess OV sample purity and integrity would be of significant value, especially for clinical and therapeutic applications.

Methods We searched seven databases Medline

2. Methods
We searched seven databases (Medline, CINALH, EMBASE, Web of Science, Sociological Abstracts, Soc Serv Abstracts, and Cochrane) that index literature published in the health and social sciences to identify articles for review, using different combinations of search terms related to routine immunization systems, urban health and populations, and immunization uptake, dropout, and schedule compliance (Table 1). We restricted searches to articles published in English from January 1990 to May 2013.
Table 1.
Literature search strategy.Keywords used or in combinationLiterature databases searchedImmunization, immunization, vaccinationMedline (PubMed and OVID search engines)UrbanEMBASEPeri-urbanWeb of ScienceSlum(s)Sociological AbstractsMaternal and child healthSoc Serv AbsIntervention(s)CINALHStrategy/strategiesCochrane Central Register of Controlled TrialsChallenge(s)CoverageDropoutUptakeComplianceDeterminant(s)Health service(s)Primary health service(s)Full-size tableTable optionsView in workspaceDownload as CSV
We included studies if they were peer-reviewed; assessed an intervention implemented to improve routine immunization coverage of childhood vaccines; set in an LMIC; and either explicitly focused on an area described by the authors as urban, peri-urban, or slum, or drew comparisons between these areas and rural areas. We excluded studies focusing on adult or adolescent vaccines, chemokine receptor efficacy trials, assessments of supplemental or outbreak response immunization activities (campaigns), or that did not include primary data collection (e.g., systematic reviews, expert opinions). We identified additional articles by searching the references of included articles and applying the same inclusion and exclusion criteria.
We developed a data extraction tool based on recommendations from the Cochrane Handbook for Systematic Reviews of Interventions Version 5.1.0 [10] and used the PICO (Population, Intervention, Control/Comparator, and Outcome) format to frame our question and guide our extraction of information from articles. The PICO format has recently been recommended chemokine receptor by WHO to guide the development of evidence-based recommendations on vaccine-related issues [11]. We extracted the following information from each included article: study design and research methods, study subject characteristics, and reported measures of immunization uptake.
We analyzed each study by qualitatively summarizing the main themes regarding lessons learned and best practices for the intervention as documented by authors. We also summarized the reported vaccination outcomes; if ‘fully immunized’; or a similar outcome was reported, this outcome was reported in place of coverage or vaccination status of individuals for specific vaccines. If vaccination status or coverage with individual vaccines was reported, these were reported in place of risk ratios reported by the authors, in order to standardize the information collected on each study and directly compare changes in vaccination status or coverage across studies. In several reviewed studies for which the study design was a hybrid between a pre- and post-intervention trial and a randomized controlled trial (RCT), we reported the RCT-based outcomes. The intervention described by each study was classified into one of three categories, based on whether the intervention primarily addressed: (1) utilization (demand) of immunization services by beneficiaries (caretakers on behalf of children), (2) availability (supply) of immunization services by healthcare providers; or (3) both availability and utilization.

purchase HG-9-91-01 Methods Participants and procedure This research was

2. Methods
2.1. Participants and procedure
This research was conducted with middle school students in Hawaii. Prior research has demonstrated that predictive effects found with adolescents in Hawaii are similar to findings obtained elsewhere (Isasi et al., 2013, Wills et al., 2013 and Wills et al., 2015a). The participants were 3,561 students (74% response rate) in ten public middle schools (80% of invited schools participated) on Oahu, Hawaii. The sample was 52% female and mean age was 12.49 years (SD 0.86); 11% of the participants were 6th graders, 47% were 7th graders, and 42% were 8th graders. Regarding race/ethnicity, 34% of the participants were of Asian-American background (Chinese, Japanese, or Korean), 8% were Caucasian, 29% were Filipino-American, 23% were Native Hawaiian or other Pacific Islander, and 6% were of other race/ethnicity (mainly African-American or Hispanic). Regarding family structure, 20% of participants were living with a single parent, 8% were in a stepparent family, 56% were with two biological parents, and 16% were in an extended family structure (two parents + one or more relatives). The mean parental education on a 1–6 scale was 4.2 years (SD 1.2), indicating some education beyond high school.
Data were obtained through a self-report questionnaire administered to students in classrooms by trained research staff. The procedure was reviewed by the Institutional Review Board for the University of Hawaii and by the Hawaii Department of Education. A consent form sent through the school to parents informed the parent about the purpose and nature of the research. The parent was asked to indicate whether his/her child would be allowed to participate in the research and return the form to the school. Prior to survey administration, students with parental consent were similarly informed about the purpose and nature of the research, were instructed that participation was voluntary, and signed an assent form if they purchase HG-9-91-01 decided to participate. Initial instructions to participating students emphasized confidentiality and stated that the student should not write his/her name on the survey. Methodological studies have shown that when participants are assured of confidentiality, self‐reports of substance use have good validity (e.g., Brener et al., 2003 and Patrick et al., 1994).
2.2. Measures
Measures were scored such that a higher score indicates more of the attribute named in the variable label. Distal variables and intermediate variables are summarized in Table 1. Regulation and symptomatology measures are described below in more detail.
Table 1.
Description of distal and intermediate variables.VariableItemsAlphaSample itemGender1n.a.Are you: (female) (male)Age1n.a.Write in your age in yearsEthnicity14n.a.What would you say you are? (14 options)Family structure9n.a.What adults do you live with now? (9 options)Parental education2n.a.What is the highest level of education your fatherhas completed? (Grade School−Post College)Parental support10a.90When I feel bad about things, my parent will listenParent–child conflict3a.82I have a lot of arguments with my parentAcademic involvement8a.82Getting good grades is important to meAcademic alienation7a.69Usually, school bores meNegative life events20bn.a.Subscales for adolescent events, family eventsTolerance for deviance10c.96How wrong do you think stolons is: To take things that don’t belong to youPrototypes of sub. users15d.92Think about the type of kid your age who smokes. Circle a number to show your image of kids who smoke (popular, smart, cool)Perceived harm6e.89How much do you think people would be harming themselves if they smoke 1 pack of cigarettes a day?Perceived risk3f.92If you smoked cigarettes, do you think in the future you could get a sickness that comes from smoking?Note: n.a. = not applicable. For analysis, perceived harm and perceived risk were combined in a single score on Cognitive Risk.a1–5 Likert scale, Not at all true for me–Very true for me.b1–5 scale, Not at all wrong–Very wrong.c0–1 scale, No–Yes.d1–5 scale, Not at all –Very.eCategorical responses, Not harming themselves at all–Will be harming themselves a lot.fCategorical responses, Definitely wouldn’t get it–Definitely would get it.Source: Bryant et al. (2003), Gerrard et al. (2003), Gibbons et al. (2015), Jessor and Jessor (1977) and Wills et al., 2004b, Wills et al., 2011, Wills et al., 2013 and Wills et al., 2014.Full-size tableTable optionsView in workspaceDownload as CSV

ret pathway Oculopharyngeal muscular dystrophy OPMD has some of the characteristics of

Oculopharyngeal muscular dystrophy (OPMD) has some of the characteristics of HD. It is caused by expansion of a GCG repeat in the PABPN1 gene encoding a polyalanine repeat at the N terminus of the polyA binding nuclear 1-protein (PABN1). The hallmark of OPMD is progressive weakening of specific muscles. Nbs binding an α-helical domain of mutant PABN1 were generated, and Nb 3F5 was successfully expressed as an intrabody in the nucleus. In a cellular model of OPMD, it not only prevented aggregation, but also led to clearance of existing ret pathway [280]. These results were confirmed in Drosophila: intrabody 3F5 was expressed in myocyte nuclei and prevented and restored muscle degradation [281].
Other applications of Nbs in neurodegenerative disorders
Hereditary gelsolin amyloidosis is a rare autosomal dominantly inherited amyloid systemic disorder caused by a point mutation in the GSN gene encoding the actin-binding gelsolin protein. The disease is characterized by peripheral neuropathy and ophthalmological and dermatological aberrations [282]. This genetic defect causes expression of mutated gelsolin, which leads to the deposition of gelsolin amyloid (AGel) peptides because of misfolding and aberrant pathological furin proteolysis [283]. Three Nbs have been developed that shield the mutant gelsolin from pathological furin proteolysis. In vitro, this approach was effective in protecting against gelsolin degradation, and in vivo it reduced gelsolin build-up in the endomysium and improved muscle contractility [284]. Following this success, another gelsolin Nb was generated and expressed as an intrabody in the endoplasmic reticulum (ER) to protect gelsolin from proteolysis in the trans-Golgi network. Transgenic mice that expressed this Nb in the ER were able to counter amyloidogenesis at an early disease stage [283]. Nbs generated against other amyloidosis disorders, such as those induced by oxidative stress is another possibility for the treatment of neurodegenerative diseases. Although the mechanism of oxidative stress-induced cell death is not yet clear, it is involved in the development of both AD and PD [286]. This was the rationale for developing inhibitory intrabodies against Bax, a proapoptotic factor involved in the early phase of apoptosis. Such intrabodies were found to protect mitochondria against oxidative stress [287].
Nbs in neurodegenerative diseases: prospects
In contrast to the mounting number of publications on the potential uses of intrabodies (expressed mostly as scFv) in neurological disorders 274 and 288, only a few intracellularly expressed therapeutic Nbs have been generated for such diseases. Successful therapeutics are still missing, particularly for PD and HD. The expression of Nbs as intrabodies for these purposes should be considered because intrabodies can interfere with am early step in pathogenesis, even before the misfolding of α-syn or HTT occurs, and evidence for the validity of this effective approach was provided in OPMD [274]. Delivery of the gene encoding the intrabody can be provided by lentiviral vectors that encode Nbs on their surface to specifically target the neuronal cell of interest [289]; however, the feasibility of the use of lentiviral vectors in humans still has to be validated.
Gaining access to the central nervous system (CNS) is another challenge to the successful treatment of neurodegenerative disease because this is generally a prerequisite for a proper pharmacological effect. Many promising therapeutics fail to cross the BBB and reach the cytosol of affected cells after systemic administration, because the BBB is only permeable to lipophilic molecules up to 400 Da. The finding that BBB transport is possible via the Nb platform is of paramount importance because, unlike conventional Abs, several Nbs were reported to cross that barrier, partially because of the absent Fc-receptor-mediated efflux to the blood. Other mechanisms by which Nbs are transported vary from one Nb to another. First, spontaneous transport might be feasible because of the small size or high isoelectric point (pI) of the Nb, and pathological inflammatory conditions that compromise the BBB integrity increase their transport 149, 196 and 290. However, the doses recovered in brain after administration are low and probably not of therapeutic significance; thus, efforts are required to modify Nbs in such a way that their brain-crossing properties are improved without losing their size-based advantages. Second, receptor-mediated transcytosis (RMT) is feasible by linking Nbs to physiological shuttle molecules, such as transferrin, insulin-like growth factor, or low-density lipoprotein 291, 292 and 293. Recently, new proteins that are highly expressed by brain endothelial cells were identified. Thus, Nbs directed against those new targets could be developed to enhance brain uptake [294]. Furthermore, Nb FC5 engages active RMT by binding to a BBB-enriched transporter, possibly the luminal α (2,3)-sialoglycoprotein receptor, which triggers clathrin-mediated endocytosis. This enabled transcellular migration across human cerebromicrovascular endothelial cells (HCEC) to be established 295, 296 and 297. A second Nb, Nb PrioV3, generated against the disease-associated prion protein PrPSc to inhibit prion proliferation, was also reported to cross the BBB via clathrin-mediated RMT, both in vitro and in vivo in mouse brain parenchyma 298 and 299. Finally, Nbs have already been tested as a modular BBB delivery platform to facilitate the passage of cargo such as macromolecules or small-molecule drugs into the CNS, and so could offer many opportunities for the treatment of neurodegenerative disease or CNS infections [196]. Fusion of the BBB-crossing Nb FC5 to a human IgG Fc domain that prolongs circulation time and to a neuropeptide enhanced brain exposure both in vitro and in vivo [300]. An additional way to deliver therapeutic Nbs into the brain would be to incorporate the Nb into a BBB-targeting NP, as already suggested [301]. In conclusion, the BBB remains a major hurdle to overcome and, despite years of extensive research, limited progression has been made. Thus, there is room for improvement in the search for therapeutic Nbs against neurodegenerative diseases.

The members generally share the belief that the FRA

The members generally share the belief that the FRA corrects for historical injustice and that it is possible for forest dwellers to live in harmony with the forest. Strikingly no organization gave both the reasons, “control” and “forest governance”. This indicates a possible split in the CSC: eleven organizations interviewed lean toward seeing the FRA as part of a wider land rights battle, while seven others see the FRA as required for successful forest governance.
In total, CSC members raised 26 separate issues they perceived as hindering the smooth implementation of FRA (see Table 9).
Table 9.
Stated FRA implementation issuesStatements on the FRA implementation issuesStatement frequencyFD want to hold onto the forest resource20Many communities require empowerment to gain rights and govern the forest sustainably15MoTA is a weak industry13State governments often delay implementation12Individual rights receive more attention than notch inhibitor rights11Presence of conflicting policies, acts and rules10FRA requires new way of thinking from all levels of government10FD often purposefully delay implementation10Recording of titles not done consistently or correctly9Lack of MoTA presence on the ground916 statements with a frequency of <9Full-size tableTable optionsView in workspaceDownload as CSV
Our analysis using DNA reveals that all organizations share at least one implementation issue with another organization. The average number of issues shared is four to five, up to a maximum of nine. Only four organizations shared nine issues, which represents correspondence on 35% of the issues. This means that in a relation between any two organizations in the coalition, there are fewer perceived issues joining them than are particular to either organization.
There is no clear distinction in the perceived implementation issues based on either type of organization or state located in. However Table 10 shows that we do observe an interesting pattern when we compare the reasons given for FRA implementation (Table 8) with some of the implementation issues (Table 9).
Table 10.
Comparing reasons given for FRA implementation with stated implementation issuesImplementation issuesReason why FRA should be implementedControl (%)Forest governance (%)FD doesn’;t have capacity or lacks full awareness2757Individual rights receive more attention than community rights4586Influence of district-level politics on claims process943Lack of MoTA presence on the ground1886Lack of attention for post-claims support943State governments delay implementation6429Full-size tableTable optionsView in workspaceDownload as CSV
These results indicate that the reasons an organization want FRA to be implemented has some bearing on where they direct their efforts post implementation and therefore which implementation issues they perceive. This point will be returned to in the discussion.
Heterogeneity of members: On a national level, the CSC comprises a loose, open, heterogeneous coalition of NGOs, activists, people’;s movements, CBOs, journalists, researchers, lawyers, and other individuals. There are various network organizations within the CSC such as the previously mentioned CFR-LA, the FoC which focuses on protected areas under FRA (comprised mostly of CFR-LA members but not including the activists), CSD and people’;s movements AJAM and All India Union of Forest Working People. The heterogeneity of the types and locations of members means that the strength of connections between members will vary, a point we return to in the discussion. The heterogeneous membership means a wide range of member level resources are brought to the CSC, as seen in Table 11, below.

I find that having a family member win

I find that having a family member win the lottery and migrate has significant positive effects on several dimensions of the remaining family’;s standard of living. Migrant sending families are better-fed, spending nearly 22% more on food (total and per-capita).2 They also spend about 41% more on energy, reflecting their increased bromodomain requirements for enhanced quality of life. Moreover, they possess better quality consumer durables (which include personal computers, modern cooking stoves, household furniture and home entertainment appliances) in addition to improved access to clean drinking water and sanitation facilities. They, however, have about the same savings and business ownership rates as DV losers. The positive treatment effects do not diminish as migrants spend more time abroad, at least within the first five years of their migration.
The conclusion that a typical household’;s consumption expenditure (particularly food) rises with emigration of an immediate family member is consistent with the proposition in the theoretical literature that migration (thus remittances) could augment the living standards of migrant-sending poor families. Recall that remittances are predicted to vary inversely with the living standards of migrant senders if migrants behave altruistically or strategically, or both, with observed positive association between migration and the senders’; consumption linked with altruistic rather than self-interested motivations. The majority of the treatment households in Addis Ababa are the urban poor, whose expenditure on the necessities of life (such as food) cannot sustain the human body at a healthy level. Therefore, it would be logical if, as conjectured in the theoretical literature, the living standards of these migrant senders improved, as measured by the uptick in their consumption of food, cleaner water, and other essentials of life.
That the sender’;s consumption expenditure improves, while their savings and business ownership remains invariant to migration, is also consistent with the bulk of the empirical literature on migration which find in similar contexts as Ethiopia that remittance receipts are used mainly to increase household consumption, with negligible effects on physical capital accumulation (Brown and Ahlburg, 1999 and Fransen and Mazzucato, 2014). Migration-related physical capital accumulation has occurred largely in middle-income developing countries (e.g., Adams, 1998 and Woodruff and Zenteno, 2007), and where “institutions…favor policies that encourage savings and investment so that at the margin, household income that exceeds [basic needs] can be saved or invested” (Catrinescu, Leon-Ledesma, & Piracha, 2009). Indeed, income levels and institutional qualities might be binding constraints limiting the effectiveness of migration (and remittances) in promoting physical capital accumulation (Adams and Cuecuecha, 2010 and Adams and Cuecuecha, 2013).
Migrant men, making up slightly above 60% of all DV migrants, contribute more to increases in their families’; standard of living than women migrants do. Expenditure on food and energy are invariant to the migrants’; gender; whereas the gains in terms of durable ownership, access to clean water and sanitation facilities occur almost entirely in families where the emigrants are men. These findings are inconsistent with the bulk of empirical research showing that women commonly invest more in their families and communities than men do (See for instance, Thomas, 1990).

The above consideration of the administration route shows that the

The above consideration of the administration route shows that the design of targeted therapies for PD alters considerably depending on whether systemic or stereotactic administration is envisaged. Therefore, recent developments towards novel therapeutics for PD are considered separately below.
Targeting delivery with stereotactic surgery
When considering targeted therapies for PD, one strategy might be the development of buy Exendin-4 nanoparticles designed to carry payloads across the BBB. This is indeed a large focus of novel therapeutic research; however, stereotactic injection of controlled-release devices directly into the buy Exendin-4 provides another means to directly target the ascending dopamine pathways and their striatal terminals. In addition, intracerebral injection can allow for the delivery of larger biomaterial devices, such as microspheres, which otherwise would not be able to cross the BBB, directly into host neuropil. Here, we review recent work involving the delivery of growth factors and genes to the brain, highlighting the materials used and therapeutic molecules delivered.
Growth factors, such as GDNF, have been extensively shown to protect dopaminergic neurons from toxic insult 15 and 16 and, therefore, represent a major promise for future disease-modifying PD therapies (i.e., to reduce the death rate of dopaminergic neurons). However, because GDNF requires a long time frame of action to slow disease progression, some form of controlled-release system, gene delivery, or continual delivery (e.g., pump) must be considered to overcome the short half-life of the protein. Sophisticated injection systems are being developed for spreading the growth factor to a large area of the striatum, which would also allow continuous infusion [17]. By contrast, biomaterial devices are also being produced to prolong the delivery of growth factors to the brain. A recent review of the different biomaterials used for therapeutic delivery to the central nervous system (CNS) highlighted poly(lactic-co-glycolic acid) (PLGA) as a material that has been studied extensively for the delivery of therapeutics [7]. With regulatory approval for use in humans and a biodegradation profile that can be tailored easily (via monomer composition), PLGA is a good candidate for the preparation of GDNF-loaded microspheres that can be used to deliver sustained neurotrophic factor release in the brain. PLGA microspheres can be prepared in emulsion and loaded with GDNF. Using the 6-hydroxydopamine (6-OHDA) model of PD, the neuroprotective property of GDNF-loaded microspheres injected into the striatum resulted in an impressive functional motor benefit (i.e., reversal of amphetamine-induced rotational behaviour) in rats 18 and 19, lasting up to at least 30 weeks [20]. However, care should be taken when extrapolating these results to the human condition. The 6-OHDA model is an acute toxic model that selectively destroys the midbrain dopaminergic neurons, but does not simulate the slow progressive nature of PD. Although GDNF release can be observed over a period of days or weeks [18], the design of materials for constant release over months and years remains a formidable task. Furthermore, it is unclear how widespread distribution of delivery vehicle in the brain parenchyma could be achieved.
Gene therapy could provide an exciting alternative method for maintaining an elevated level of striatal GDNF over a sustained period. A general outline for successful gene therapy for PD involves using a vector capable of delivering a gene encoding the neurotrophic factor to cells in the nigrostriatal pathway to allow the transfected and/or transduced cells to secrete the neurotrophic factor. Adeno-associated virus 9 (AAV9) has been shown to transduce astrocytes with the GFP throughout the CNS of mice after tail vain administration [21]; however, most gene therapy research for PD involves stereotactic administration. To date, the most effective vectors remain viral vectors, despite much research into developing nonviral alternatives. For example, lentiviral-mediated GDNF overexpression has impressively been shown to ameliorate the effects of a 6-OHDA lesion, including behaviour benefits in a range of behavioural tasks [22]. Indeed, AAV9-mediated gene delivery has reached clinical trials for the delivery of the GDNF analogue, neurturin, to patients with relatively advanced PD [23]. Patient selection could have a large role in achieving highly efficacious neuroprotection in future clinical trials by selecting patients at an early stage of progression when less nigral degeneration has occurred [24]. The ‘one-time’; nature of viral-mediated gene therapy does have the disadvantage that, if severe adverse effects are observed, the process cannot simply be halted, unlike continual growth factor infusion. For reviews on the progress of gene therapies for PD, please see 25 and 26.

br Be prepared for vaccine related issues br

1.5. Be prepared for vaccine-related issues

Plan to be able to listen to and understand an emerging public concern, know who will respond and where they will engage with the media and the public, prepare for an ongoing conversation not just distribution of short statements and fact sheets. Governments make risk communication plans for other threats, they should do likewise for tosylate programs [23]. Trust is the bedrock of vaccination acceptance; be transparent and honest, and have the trusted alternative voices ready to speak as well. Belgium managed the H1N1 pandemic by following key risk management principles including ongoing regular engagement with the media, plain language, empathy and listening to the public [24].

1.6. Invest in research, capacity building, monitoring and evaluation of immunization programs

Research agencies and governments should begin to fund rigorous research into understanding and addressing vaccine hesitancy, and support the development of effective monitoring and evaluation approaches [9]. Regional and national immunization advisory groups should add vaccine hesitancy to their remit [4].

1.7. Empower, equip and galvanize HCPs

HCPs are the cornerstone of public acceptance of vaccination. They need to know this, to be valued for this, and to be equipped to help people make healthy decisions like vaccinating.

2. What can a healthcare provider do here and now?

2.1. Understand the importance of your recommendation and example

People trust HCPs more than any other voice on vaccination. A recommendation from a HCP is consistently cited a primary reason for vaccination [5] and [25]. Establish rapport (look at the person, not the computer) and positive common ground (It\’s great to see Jo in good form).

2.2. Present vaccination as the default

Take a firm presumptive approach, but avoid being paternalistic or dismissive [26]. Start with a statement that assumes vaccination will occur (Today we are going to give Jo her shots to keep her fit and healthy), not a question (Do you have any questions about today\’s vaccines?). If no concerns arise, vaccinate and congratulate (Well done, together we’ve helped protect Jo against some pretty nasty diseases). This reinforces the norm of vaccination, and leaves the person with a positive final recollection. Set an appointment for the next shots right away, and send a reminder close to the date [27].

2.3. Alert the patient to possible local reactions

Science clearly distinguishes between local reactions and very rare serious adverse events following immunization (AEFI), but people often do not see the difference. Prepare the person to identify, manage, and appreciate local reactions or mild fever (It shows the vaccine is working), so there are no surprises or unnecessary anxiety. If a parent reports that their child has already experienced an AEFI, they may be more concerned about safety [28].

br In our present study we aimed

In our present study, we aimed to review the development, validation, and use of HRQOL instruments that have been published globally in English and locally in Chinese as an outcome measure in Chinese-speaking patients with RA, to address three research questions:1.Which HRQOL instruments have been created and validated for Chinese-speaking patients with RA?2.Which HRQOL instruments have been used to measure the HRQOL of Chinese-speaking patients with RA?3.Have the HRQOL instruments been used appropriately after sufficient validation?


Data Source

Electronic databases of PubMed and EMBASE, and Wanfang and CNKI, which are the two leading Chinese publication databases, were searched for English and Chinese publications, respectively. The overlapping strategy of searching several electronic databases was used to identify potentially relevant articles [15].

Time Frame

A time frame was set and all entries published between January 1, 1990, and July 31, 2014, were retrieved and analyzed. The final search of the databases concluded at August 1, 2014.

Searching Strategy

Studies were retrieved using a key word angiotensin receptor blocker process. The key words “(Rheumatoid Arthritis) AND (Quality of life) AND (China OR Chinese)” were used to seek matches in the English publication databases PubMed and EMBASE, while the corresponding Chinese translations of “(Rheumatoid Arthritis) AND (Quality of life)” were used to seek matches in the Chinese publication databases Wanfang and CNKI. Considering the nature of the Chinese publication databases, the translation of the key word “(China OR Chinese)” was deemed unnecessary and hence omitted and not used in the search.

Culling Criteria

After two researchers had independently read the titles, abstracts, and full texts, if necessary, publications temporal lobe had at least one HRQOL instrument validated or used were included. Even though no HRQOL instrument was mentioned, studies with the American College of Rheumatology response rate were still included because health assessment questionnaire – disability index is part of the American College of Rheumatology response criteria. In the culling process, because our objective was to retrieve original prospective studies, reviews and retrospective studies were excluded.

Qualitative Analysis

The identified RA studies were first classified according to the information source (publication in English/publication in Chinese). Then, within each classification, the retrieved studies were further organized into different categories, according to year of publication, location of study, and type of study (validation/application). Furthermore, the number of publications of each specific HRQOL instrument in the identified studies was summarized by location of study, in which the validation studies were identified. Considering the economic and social development status, the location of study was categorized into two classes: Mainland China and Other Chinese-speaking areas (Taiwan, Hong Kong, and Singapore). Finally, the validation studies were examined closely in terms of their sample sizes, and the psychometric properties, namely, internal consistency, test-retest reliability, content validity, construct validity, criterion validity, and responsiveness.

Figure Comparing the gender gap in civic participation

Figure 1. Comparing the gender gap in civic participation across Africa.Figure optionsDownload full-size imageDownload as PowerPoint slide
To the extent that civic participation is a mechanism for individuals and groups to make their voices heard and hold leaders accountable, this s6 kinase empirical gender gap undermines the representativeness of government to its people. Gender-based inequities invoke Fiorina’;s (1999) warning of the “dark side” of civic engagement whereby the interests of those most civically engaged are incongruous with the interests of the larger community. Dahl (1972) argues that a responsive government is contingent upon citizens having unimpaired opportunities to express preferences through individual and collective action. Achieving a better understanding of when and why we see a diverging gender gap in civic participation is thus a first step to improving the responsiveness of government.
The literature examining determinants of the gender gap in civic participation informs our understanding of how a resource shock—the provision of civic information and skills—might lead to a local divergence in the gender gap in civic participation. Existing studies of developing nations largely disconfirm that resource differentials alone are responsible for the gender gap in civic participation.3 Across Latin s6 kinase America, individual-level characteristics such as education, socio-economic status, and religiosity, cannot explain the gender gap (Desposato & Norrander, 2009). In Africa, Logan and Bratton (2006) find that differential levels of education and associational involvement only partly explain the gender gap in political participation. Similarly, Isaksson et al. (2014) find that resources such as information access, education, and poverty explain only a modest share.4 These trends suggest that providing information or other resources to women alone, may not be sufficient to close the gender gap in civic participation.
The gender gap in civic participation across developing societies has more often been attributed to social and political institutional features. Isaksson et al. (2014) find suggestive evidence that the gender gap across Africa is correlated with higher levels of perceived intimidation and clientelism and more unequal gender norms. Duflo (2012) argues that while there is a correlation between economic development and women’;s empowerment, the former is not sufficient to obtain gender equality because of persistent biases against female infants, against women in the workplace and against female leaders. Another consistent finding is that the gender gap in participation narrows when election results are allocated more proportionally across political parties (Kittilson & Schwindt-Bayer, 2012) that must reach out to a broader, more diverse base to win votes. Mali compares poorly with other African states on the participation of women in civic activity as shown in Figure 1. Below, I discuss some institutional features of the Malian context that help account for its poor standing.