Teams were instructed to use the marked vials first From the sec

Teams were instructed to use the marked vials first. From the second day of the campaign, teams indicated the number of marked and unmarked vials they took with them at the start of each day on their CTC monitoring form. As this was the first use of CTC in a mass campaign, and in order to ensure the tools

were being properly used, six additional supervisors were recruited to oversee campaign activities and provide support to vaccinators. The data on coverage, vaccine wastage and adverse events following immunization were collected using standard Ministry of Health issued forms. Data on CTC specific vaccine wastage was collected through the specially designed CTC monitoring form, described above. At the Duvelisib end of the campaign a survey was conducted to evaluate the CTC practice among the vaccinators and supervisors in Banikoara. The survey was pre-tested with vaccinators prior to being administered. The survey included 20 multiple choice and short answer questions. Three different CTC scenarios were implemented in the campaign, based on the situation found in Banikoara. The first scenario was the most standard option, used by all three dispensaries and seven of the health centres. It involved

keeping the vaccines in the standard cold chain at the health centre. This meant the vaccine was transported from the district level to the health centre using the cold chain and placed into the fridge at district selleck inhibitor level. On the first morning of the campaign, vaccination teams arrived at the health centre and retrieved their vaccines. The vaccines were placed into a standard vaccine carrier, without icepacks, marking the beginning of the CTC practice. The second scenario was used in two health centres to enable access to remote communities with no reliable electricity or power Cytidine deaminase source, accessible only by difficult to navigate roads. In

other non-CTC campaigns, teams had to return each night to the health centre to maintain the cold chain, limiting their ability to reach the most remote areas. With the CTC practice, the teams collected their vaccines from the health centre, as described above, and set out for the remote villages. However rather than coming back each night, they stayed in the villages for three days, enabling them to ensure better vaccination coverage of the population. The third scenario involved starting CTC at the point when the vaccines were transported from the district to the health centre level. This was used in the one health centre that did not have any functional cold chain equipment. While in previous campaigns they had to make a daily trek to the district capital to collect their vaccine, during this campaign vaccines were transported from district to the health centre in a CTC, and then stored in a CTC for four days, at which point a new drop off of vaccines was needed.

In June 1988 the EACIP became a separate committee consisting of

In June 1988 the EACIP became a separate committee consisting of 26 experts. In October 1992 and March 1997, the China EACIP members were reelected and the membership expanded to 28 and 30 experts, respectively, Birinapant in vitro appointed by the MOH. The latest election to the China EACIP was made in October 2004, as described

below. The members of the EACIP are nominated and appointed by the MOH. Tenure is valid until reelection. The Chair and assistant Chairs are similarly appointed although they serve in an honorary capacity. From October 2004, the EACIP consisted of 33 members: one Chair, three assistant chairs, 26 members with expertise in specific disciplines, and three secretaries. Membership selection criteria include: expertise in research and development of vaccines, testing and approval of vaccines, pediatrics, infectious diseases, immunology, management of health policy, public health, epidemiology and statistics, ethics, and health law. In addition, consideration is given to membership being representative of different

regions and social and economic status. EACIP does not have any members in observer status, and none of its members are officers of the MOH. The duties of CP 690550 the EACIP are wide ranging and include: formulation and modification of immunization regulation and strategies; advising the MOH on important strategies related to immunization; conducting field surveys and assessments to aid decision-making; and providing recommendations regarding personnel training and scientific exchange under the leadership of the MOH. The China EACIP carries out its role to provide technical advice relevant to immunization under the leadership of the MOH. The Department of National Immunization Program (NIP) of the Chinese Center for Disease Control and Prevention (CCDC) is responsible for the routine secretarial work of the EACIP. Its functions include obtaining background documents and literature

collection, data review, assisting the MOH to set the agenda, coordinating meeting logistics, writing minutes, drafting reports, routine communication with EACIP members, and other activities. Fig. 1 shows the relationship between EACIP, MOH and CCDC. The EACIP carries out its activities through four different science mechanisms: (1) plenary meetings involving all members, which are held once annually and initiated by the MOH; (2) working group meetings involving only some of the EACIP members, which are held by the MOH and the CCDC to resolve one or more specific technical issues; (3) correspondence meetings, which involve the circulation of written papers and documents about issues that need to be resolved with the collection of opinions of the EACIP experts; and (4) specific field surveys and supervision, with relevant experts participating at the invitation of the MOH or the CCDC. During each of these activities, members should avoid participating if there is considered to be any obvious conflict of interest.

8 Amala et al 9 conducted a preliminary study to confirm the anti

8 Amala et al 9 conducted a preliminary study to confirm the anti inflammatory activity of I. aspalathoides tender shoots. However, no systematic approach has been done so far to analyze phytochemical constituent that contribute anti inflammatory activity of I. aspalathoides.

In the present study, the systemic study combining phytochemical and pharmacological aspects was carried INCB018424 molecular weight out to evaluate the anti inflammatory of I. aspalathoides using Swiss albino mice. Plant sample was collected from Gopalasamy Hills in Viruthunagar district, Tamil Nadu, India. This plant was authenticated and voucher specimens were deposited in the Department of Biotechnology, Sri Kaliswari College, Sivakasi. The stems were shade-dried and pulverized. The powder was treated with petroleum ether to remove wax and chlorophyll and extracted with methanol. The extracts were concentrated by distilling

the solvent in a rotary flash evaporator. Methanol was evaporated and dried extracts were dissolved in water. Swiss albino mice, (20–32 g) aged 8–12 weeks were used for anti inflammatory studies. They were kept hygienically in polypropylene cages in a controlled environment (Temperature 25 ± 2 °C, relative humidity 65 ± 10%, and 12 h dark/light cycle) with standard laboratory diet and water ad libitum. This study was conducted after obtaining institutional animal ethical committee clearance (Number: 1086/AC/07/CPESEA). The acute toxicity (LD50) of the EIA was determined in mice by Lorke method.10 find more The study was carried out as per the guidelines of OECD (Number: 1086/AC/07/CPESEA).

The anti inflammatory activity was assessed using Winter et al method.11 The selected Swiss albino mice were divided into five groups of six animals (n = 6) each and housed under laboratory condition. Group 1: control–carrageenan (0.1 mL of 1%) only The percentage of inhibition of paw edema was calculated using following formula, Percentageofinhibitionofpawedemavolume(%)=1−(Vt/Vc)×100 Linifanib (ABT-869) Vt = Paw edema volume of drug treated group Biochemical changes in carrageenan induced paw edema were estimated in an interval of 6 h. The blood was collected from anaesthetized mice by cardiac puncture. The serum was separated from blood sample. The separated serum was analyzed for lysosomal enzymes such as SGOT and SGOT described by Woessner method.12 The activity of SGOT and SGPT were expressed in U/mL. The 0.8 mL of blood was collected from each group of mice by using sterile syringe via cardiac puncture and put into the tube which contained EDTA and mixed with the 0.2 mL of 3.8% of sodium citrate solution in a test tube. The Westergren tube is filled up to ‘0’ mark with citrated blood and plasma vertically in the stand. The sedimentation of RBC in mm in 1 h is observed and compared with other groups. 300 mL of water were added to the stem powder of I. aspalathoides (15 g) and heating was carried out a micro oven.

C Cutland, Dr M Groome, Dr V Gosai (Diepkloof and

El

C. Cutland, Dr. M. Groome, Dr. V. Gosai (Diepkloof and

Eldorado Clinics); Dr. E.V. Aghachi (Bertoni Clinic), Dr. N. Nyalunga, Dr. F. Kiggundu (Lethlabile Clinic), Dr. C. Werner, Dr. F. Scholtz (Oukasie Clinic), Dr. T.J. Botha, Dr. M. Venter (Karenpark Clinic); S. Qolohle (Project Manager), D. Traynor(Operations Manager), A. Venter, I. Groenewold, Dr. T Sithebe, M. Sauerman (Site Managers). Erin Kester (PATH) is thanked for assisting with the manuscript preparation. We acknowledge DDL Diagnostic Laboratory, the Netherlands for performing RT-PCR followed by reverse hybridization assay and/or sequencing to determine rotavirus G and P types. GSK Rota037 study-team is acknowledged for contributing toward assistance in protocol development, study conduct, data analysis and manuscript review. Rotarix is the trademark of GlaxoSmithKline group of companies; RotaTeq is the trademark of Merck & Co., Inc.; Rotaclone is a trademark of Meridian Bioscience. click here Contributions: SAM, KMN and ADS were involved in the study

conduct; reviewed check details all relevant literature; were involved in developing study methods; contributed to data analysis and prepared the first draft. MK, CL, PB, SA played key roles in study conduct; critiqued the study methods and assisted in editing the manuscript; provided several additional critical reviews of the draft manuscript at various stages. AB was involved in study design, development of study organization and methods and part of the study conduct as employee of GSK. Conflicts of interest: SAM has received research grants and honoraria from GSK and MERCK. The primary analysis as per analysis-plan was undertaken by GSK, with additional analysis undertaken by SAM. Disclaimer: The views expressed in this publication are those of the authors alone and do not necessarily represent the decisions, policy, or

views of the National Institute for Communicable Diseases, Sandringham, South Africa; Department of Science and Technology/National the Research Foundation; Pretoria, South Africa or PATH, Seattle and Sanofi Pasteur. Disclosure: All authors have approved the final article. PATH’s Rotavirus Vaccine Program, funded by a grant from the GAVI Alliance, and GlaxoSmithKline (GSK) Biologicals, Rixensart, Belgium, were the study sponsors and GSK Biologicals was responsible for administrative aspects of the study, including clinical trial supply management, data management, analysis and reporting. The funding source had no involvement in the research, writing, or the decision to submit the paper for publication. “
“Africa accounts for approximately 60% of the approximately 1.3 million annual diarrhea-related deaths worldwide [1] and [2]. In Kenya in 2008, it was estimated that greater than 38,000 diarrhea-related deaths occurred, which was 20.5% of all deaths [1]. Rotavirus is the most common etiology of childhood diarrhea deaths in Africa [3]. WHO estimates that in 2004, approximately 7500 rotavirus deaths occurred in Kenya [3].

These time points were chosen in order to estimate the impact of

These time points were chosen in order to estimate the impact of the treatment on acute/necrotic and late/apoptotic cell death (Fujikawa, 1996 and Weise et al., 2005). Rats were anaesthetized Antidiabetic Compound Library order with chloral hydrate and transcardially perfused with a solution of paraformaldehyde (PF 4%) in phosphate buffer (PB 0.1 M). The brains were removed immediately after perfusion and post-fixed with a solution of PF 4% and sucrose

(30%) in PB 0.1 M. Fifty-micron coronal sections through the entire extension of the hippocampus were obtained using a cryostat (−18 °C), mounted on glass slides, and stained with cresyl violet (Nissl). The estimative of total number of neurons in the CA1 hippocampal sub-region and the hilus of the dentate gyrus was obtained in five animals per group using the stereological method optical fractionator (West et al., 1991). Briefly, every fifth section was selected, resulting in a section sampling fraction of 0.2 (ssf = 0.2). In each section, the hippocampal subfield CA1 and the hilus of the dentate gyrus were identified according to a brain atlas ( Paxinos and Watson, 1982). Disector counting probes (25 μm × 25 μm) were uniform and randomly distributed through

the hippocampus (right and left). Each disector correspond to an area (a) of 625 μm2 and the distance between counting frames (x,y step) was 250 μm, resulting in an area sampling fraction of 0.01 (asf = 0.01). Neuronal cell bodies (tops) were counted through the entire thickness of each section, resulting in a thickness sampling fraction of 1 (tsf = 1). Alisertib The estimative of total neuronal cell number (N) for each region was calculated using the formula ( West et al., 1991): N=∑Q−⋅1ssf⋅1asf⋅1tsfwhere ΣQ− is the number of counted neurons, tsf is the thickness sampling fraction, asf is the area sampling fraction, and ssf is the

section sampling fraction. A pilot study showed that this sampling scheme produced acceptable coefficients of error (CE) and variance (CV) ( West et al., 1991 and Keuker et al., 2001). Caspase-1 and -3 activities else were studied in five animals per group using the method described by Thornberry et al. (1997) and modified by Belizario et al. (2001). Rats were killed, hippocampi were dissected at 4 °C and added to 20 mM HEPES buffer (pH 7.4) that contained 2 mM EDTA, 0.1% CHAPS, 10% sucrose, 0.1% PMSF, 0.1% benzamidin, 0.1% antipain, 0.1% TLCK, 0.1% chemostatin and 0.1% pepstatin (5 μl homogenization buffer/mg tissue). Homogenates were obtained by mechanically disrupting the tissue three times on dry-ice, with thawing in an ice bath, interpolated by 1 min of moderate vortex shaking. Samples were centrifuged at 12,000 × g for 40 min at 4 °C to remove cellular debris. Total proteins were determined in the supernatants using the Bio-Rad Protein Assay (Bio-Rad Labs, Germany).

While we suggest that rational deliberation [21] must occur in or

While we suggest that rational deliberation [21] must occur in order to ensure that the ethical tensions are acknowledged and addressed, we do not suggest that this set of considerations is exhaustive or decisive.

The empirical context is directly relevant to bioethical deliberation, as there may be morally relevant facts that can inform how to weigh these considerations. Having said this, we agree with Verweij and Dawson that despite the fact that decisions are taken within a specific regulatory context in which there are empirical facts that need to be taken into account, “some agreement can be reached about which general norms should guide”, even when agreement about the interpretation Selleck Trametinib of the ethical considerations remains contested [11]. We thus propose these ethical considerations as a starting place for ethical reflection and as a means to fostering deliberation, not closing down discussion. The utility of these considerations will require evaluation, as the conceptual nature of this research will require further refinement through empirical research and input from a community of scholars and regulators and the public [3]. It is hoped that these considerations will encourage regulators and researchers charged with the post-market monitoring of vaccines to consider the explicit articulation

of values in the decision-making and research-shaping process in this context. This research was funded L-NAME HCl by a Canadian Institutes of Health Research Catalyst Award no. 264153 from the Drug Safety and Effectiveness Network. Conflict of interest statement We declare that we HIF inhibitor have no conflicts of interest,

and that the funder (Canadian Institutes of Health Research) had no say in the design, interpretation or conclusions of this research. “
“Global eradication of disease has fired the imagination since the introduction of vaccination, a possibility that Jefferson brilliantly expressed in his letter to Jenner: ‘Medicine has never before produced any single improvement of such utility… Future nations will know by history only that the loathsome smallpox has existed and by you has been extirpated’ [1]. Whilst it was over 170 years before Jefferson’s dream was realised, smallpox was indeed globally eradicated by the end of the 1970s, and remains an iconic achievement of the twentieth century. In general, to eradicate a disease is to reduce to zero the incidence of the disease through deliberate efforts [2]. To eradicate a disease globally is to remove the disease threat from the whole world, permanently: in a recent consensus definition, “the worldwide absence of a specific disease agent in nature as a result of deliberate control efforts that may be discontinued where the agent is judged no longer to present a significant risk from extrinsic sources (e.g. smallpox)” [3]. This paper is concerned with the ethics of global disease eradication.

The seeds were sown at 25 days intervals on 20th May, 15th June a

The seeds were sown at 25 days intervals on 20th May, 15th June and 10th July, 2010 in the experimental plots with 60 × 30 cm spacing. All agronomical management practices were performed as needed. The samples click here of leaves and whole plants were collected at pre flowering and full flowering stages. Samples of whole plant, leaves, spikes and husk were subjected to hydro-distillation for 4 h using a Clevenger-type apparatus to produce oil. The oils were dried over anhydrous sodium sulphate and stored in sealed vial at low temperature before analysis. GC/MS analyzes were performed with a Perkin Elmer Clarus 500 gas chromatograph

equipped with a split/splitless injector (split ratio 50:1) data handling system. The column was Rtx®-5 capillary columns (60 m × 0.32  mm, 0.25 μm film thickness). Helium (He) was the carrier gas at a flow rate 1.0 ml/min. The GC was interfaced with (Perkin Elmer Clarus 500) mass detector operating in the EI+ mode. The mass spectra were generally recorded over 40–500 amu that revealed the total ion current (TIC) chromatograms. Temperature program was used as follows: initial temperature of 60 °C (hold: 2 min) programmed at a rate of 3 °C/min to a final temperature of 220 °C (hold: 5 min). The temperatures of the injector,

transfer line and ion source were maintained at 210 °C, 210 °C and 200 °C, respectively. The components of the oils were identified by comparison of their mass spectra with those selleck chemicals llc of commercial libraries (NIST/Pfleger/Wiley)

or with authentic compounds and confirmed by comparison of their retention indices either with those of authentic compounds or with data published in literature. 17 The average oil content in different plant parts were obtained as 0.06–0.10% (whole plant), 0.10–0.14% (leaves), 0.13–0.23% (spike) and 0.10–0.13% (husk) during different sowing times. The highest oil content obtained in all the spike samples at different sowing times, which ranged from 0.16 to 0.23% (D1), 0.15–0.20% (D2) and 0.13–0.18% (D3), whereas lowest oil yield obtained in whole plant, varied between 0.06 and 0.09% (D1), 0.06–0.10% (D2 and D3). Table 1 shows the identified constituents and their relative content in the essential oils obtained DNA ligase from whole plant, leaves, spikes and husk of Perilla frutescens at 3 sowing times, D1-seeds sown on 20th May, D2-seeds sown on 15th June and D3-seeds sown on 10th July. D1 stage: The major compound was found as perilla ketone (52.34–90.28%) followed by 1-methyl-2-methylene trans-decalin (4.49–32.98%). The percentage of perilla ketone, the first major compound in all the oils, was found maximum in spikes (90.28%) followed by husk (64.54%), leaves (54.56%) and whole plant (52.34%). 1-Methyl-2-methylene trans-decalin was higher in leaves oil (32.98%) and lower in spikes essential oil (4.49%). The amount of trans-caryophyllene was higher in the essential oil obtained from whole plant (8.54%) and also in husk (5.08%).

Furthermore, the SPECT/CT images indicated that the NFC hydrogels

Furthermore, the SPECT/CT images indicated that the NFC hydrogels did not degrade or deform as no pertechnetate was observed outside the site of injection, which is supported by the previous studies on cellulose biodurability (Märtson et al., 1999), flexibility, and structural integrity (Pääkkö et al., 2008). As a non-biodegradable material in the mammalian body, NFC could find potential use as a surgical tissue adhesive, space-filling injectable biomaterial

for tissue repair, long-term or single-dose local drug delivery, and tissue engineering. However, non-biodegradability is generally not desired. The removal of NFC from easily accessible sites (such as from subcutaneous tissue) through surgical means is fairly simple. In addition, the area could be locally treated with cellulose degrading enzymes to disintegrate the NFC hydrogels yielding mostly glucose as Pifithrin-�� the metabolized product. It has been shown that enzymatic degradation of NFC with cellulase is possible without increasing in vitro cytotoxicity ( Lou et al., 2014). However, patient acceptance towards injections is generally poor. Therefore NFC hydrogels have potential

as long-term or single-dose local delivery systems, especially with compounds of poor bioavailability or Galunisertib clinical trial where non-invasive routes remain a challenge. The release and distribution of 123I-β-CIT (a cocaine analogue) from NFC hydrogel implants were evaluated. 123I-β-CIT showed rapid release from the hydrogels, mostly distributing into the striatum and slightly around the hydrogel at the injection site. 123I-β-CIT showed a slightly slower rate of release when Adenosine imbedded with the hydrogel as opposed to the injections of saline and drug compound solutions. However, due to the rapid release, we determined that 123I-β-CIT does not show an apparent binding affinity to nanofibrillar cellulose itself. In addition, no major differences were found in the distribution of 123I-β-CIT

between the NFC/study compound injections and the saline/study compound injections. Therefore it is possible that the release of similar small compounds might not be altered by the NFC matrix. However it seems that the NFC hydrogel retains most of the 123I-β-CIT around itself and does not distribute as easily into the surrounding subcutaneous tissue than with the saline injections. We found it interesting that without affecting much of the release rate of the study compound, 123I-β-CIT is still more localized when administered with NFC. The release rate of the 99mTc-HSA was shown much slower than the release rate of the smaller study compound 123I-β-CIT. In addition, a very poor absorption from the injection site into the circulation was observed; furthermore, 99mTc-HSA distributed heavily into the surrounding subcutaneous tissue.

In addition to rescue/recovery workers, the Registry includes Low

In addition to rescue/recovery workers, the Registry includes Lower Manhattan residents, area workers, school staff and students, and commuters and passersby on 9/11. The Registry’s recruitment methods have been described previously (Brackbill et al., 2009 and Farfel et al., 2008). At the time of enrollment, registrants completed a Wave 1 (W1) baseline computer-assisted SB203580 datasheet telephone (95%) or in-person (5%) interview about their 9/11-related exposures and health following the disaster (Farfel et al., 2008). Two subsequent surveys have been conducted to obtain updated information on enrollees’

health status, healthcare utilization, and well-being. RG7204 chemical structure Both employed mail, web and telephone survey modes. The Wave 2 (W2) survey was conducted from November 2006 through December 2007 with a response rate of 68% (Brackbill et al., 2009). Wave 3 (W3) was conducted from July 2011 through March 2012, with a response rate of 63%. The Registry protocol was approved by the Centers for Disease Control and Prevention (CDC) and New York City Department of Health and Mental Hygiene institutional

review boards. Enrollees provided verbal informed consent to participate in the Registry. Diabetes was defined as self-reported diabetes diagnosed after Registry enrollment, reported at either W2 or W3, by answering “yes” to the question, “Have you ever been told by a doctor or other health professional that you had diabetes or sugar diabetes?” Additionally, the year of diagnosis had to have been greater than or equal to the year of W1 completion. For those

who reported diabetes at both W2 and W3, the year reported at W2 was used. The surveys did not specify type 1 or type 2 diabetes; however, as the study sample only included adults, and type 2 accounts for 90% to 95% of adulthood diabetes diagnoses (Centers for Disease Control and Prevention, 2011b), we assumed the vast majority of reported cases were type 2. The main predictor of interest for this study was PTSD at W1. We used a 9/11-specific PTSD Checklist (PCL), a validated, 17-item, event-specific scale, to assess symptoms of PTSD in the 30 days preceding the interview, with some questions specifically referencing STK38 the events of 9/11. The PCL has been reported to have a sensitivity of 94% and specificity of 86% (Blanchard et al., 1996 and Weathers et al., 1993). PTSD was also measured at W2 and W3. Individual items were scored from 1 (not at all) to 5 (extremely), with total scores ranging from 17 to 85. PTSD was defined as a score of 44 or greater, with no items missing. Additional covariates included sociodemographic variables and 9/11-related exposures. Data on sex, age, race/ethnicity, education, and smoking status were obtained at W1.

A major public health implication of this interference is the acc

A major public health implication of this interference is the accumulation of a cohort of susceptible

subjects long before the age recommended for revaccination. That could possibly affect disease control, particularly of yellow fever, for which revaccination every 10 years is recommended, disregarding the age at primovaccination and the weaker immune response in infants [6], [20] and [25]. Similar to the results of this study, a multicenter study with the 17DD substrain vaccine showed 88% seroconversion in children aged 12–23 months and 72% in infants aged 9–11 months [6]. At the time that study was conducted the monovalent measles vaccine was administered at 9 months of age. As the study outcomes relied on serological tests the implications of their accuracy results should be considered briefly. PRNT is the “gold standard” for detection www.selleckchem.com/products/pci-32765.html of measles [38] and of yellow fever antibodies [39], but for yellow fever it lacks the level of standardization of measles PRNT [15] and commercial tests such as those used for rubella and mumps antibodies.

The proportion of reduction in number of plaques with neutralization, for instance, might affect the sensitivity of the PRNT and partly explain the variability of GMT across studies. Nevertheless, seroconversion may be a more robust measure of response to immunization. The pre-vaccination seropositivity for Selinexor cell line yellow fever could indicate false positive results of the PRNT, previous vaccination held outside the Federal District where the vaccine is given at 9 months of age, and to maternal antibodies

[40]. Randomization safeguarded against selection bias but misclassification of seropositivity might have weakened the differences between groups. However, with seroconversion as the outcome we focused on the variation in the immune status after vaccination and made enough allowance for pre-vaccination seropositivity. Systemic adverse events following simultaneous administration of the vaccines had a similar pattern observed after the vaccine against yellow fever was given separately. The time of onset of symptoms, as well as its duration is compatible with events related to vaccination, but there is no way to distinguish them from signs and symptoms of coincidental clinical conditions. The frequency of adverse events following immunization was consistent with that reported in the literature for yellow fever [41], except for fever, which was about twice as high. The higher frequency of signs/symptoms was a plausible outcome of simultaneous vaccination with four viral agents. Neutralizing antibodies against rubella are generally considered the protective immune response [42]. As titration of these antibodies is not routinely available, antibody levels (≥15 IU) measured by other methods are considered to protect against rubella infection [43].