3-(4-dimethylaminophenyl)-N-hydroxy-2-propenamide

Archived P. vivax positive DNA samples collected in the course of earlier studies conducted between 2003 and 2007 were used [13] (link), [14] (link), [15] (link), [16] (link). At the start of our comprehensive microsatellite typing project, information on multiplicity of infection (MOI) was available for samples from PNG based on the two P. vivax genotyping markers MS16 and msp1F3 [17] (link). MS16 showed the highest resolution of all markers, in addition our previous work showed that underestimation of MOI is unlikely when these two markers are typed [18] (link). Results from MS16 and msp1F3 thus provided the basis for the selection of preferentially single clone infections or low multiplicity samples for further analysis. Details of samples used in this study and their origin are listed in Table 1.
295 P. vivax positive blood samples from four sites in PNG and one site on Solomon Islands were included in the study. Three of the study sites in PNG were located in the hyper- to holoendemic tropical lowlands: Ilaita (n = 132 samples) and Kunjingini (n = 38, both Maprik District, East Sepik Province) and Alexishafen (n = 45, Madang Province). The fourth PNG study site was in a meso-endemic site at the Southern highlands fringe at an altitude of 1100 metres (n = 39, Sigimaru, Karimui area, Simbu Province) (Figure 1).
Large parts of the coastal lowlands of PNG are characterized by high prevalence of P. vivax and P. falciparum with perennial transmission and mild seasonal variation. In study participants from the Ilaita site, prevalence by microscopy was 44.3% for P. vivax, 32.6% for P. falciparum and 4.2% of P. malariae. The incidence rate of malaria was 2.46 episodes per child per year for P. vivax and 2.56 for P. falciparum[15] (link). Malaria prevalence is lower in the highland fringe of Simbu province. In a survey in 2001–2002 prevalence was 8% for P. vivax and 27% for P. falciparum in South Simbu, where our study site is located [19] (link).
Solomon Islands samples (n = 41) derived from asymptomatic children >6 months and adults from the Tetere area (Guadalcanal Province), collected in 2004 and 2005 [16] (link). At that time transmission of P. falciparum and P. vivax in the area was considered mesoendemic. P. vivax prevalence by microscopy was 19.1% compared to a P. falciparum prevalence of 12.9% ([16] (link) and Marie Ballif, unpublished results).
Preliminary analysis of longitudinal data from the Ilaita cohort showed no changes in diversity or structuring of samples over time. Thus, the collection of samples in different years is not expected to influence the results.

The study was undertaken within the framework of the assessment of the community effectiveness of Intermittent Preventative Treatment in Infants (IPTi), part of the IPTi Consortium (www.ipti-malaria.org, clinical trial number NCT00152204). We received ethical approval from local and national institutional review boards (Ifakara Health Institute and the National Tanzania Medical Research Co-coordinating Committee) through the Tanzania Commission for Science and Technology. Ethical and research clearance was also obtained from the London School of Hygiene and Tropical Medicine, UK, and the Ethics Commission of the Cantons of Basel-Stadt and Basel-Land, Switzerland. During field work, information sheets in Swahili about the study were given out, explaining why it was being done, by whom, and what it would involve. Consent to participate was obtained in writing from household heads and orally from women answering questions about their pregnancies. Confidentiality of all study participants was assured.
The study was conducted in the districts of Nachingwea, Lindi Rural, Ruangwa, Tandahimba and Newala Districts in Southern Tanzania, which had a total population of over 800,000 people in 2007. The study setting and field methods from a similar survey have been described in detail elsewhere [15] , [16] (link) so the key aspects are summarised here. The area has a wide mix of ethnic groups, including the Makonde, Mwera, Yao. Although most people speak the language of their own ethnic group, Swahili is also widely spoken. The most common occupations are subsistence farming, fishing and small scale trading. Cashew nuts, sesame and groundnuts are the major cash crops while food crops are cassava, maize, sorghum and rice. Most people live in mud-walled and thatched-roof houses; a few houses have corrugated iron roofs. Common water supplies are hand-dug wells which rely on seasonal rain, communal boreholes, natural springs and river water. Most rural roads are unpaved: some are not passable during rainy seasons while others are too steep for vehicles to pass. In 2000–2001 39% of households lived below the poverty line in Lindi and Mtwara regions [27] . The HIV prevalence rates (categorized) for adults age 15–49 years in Lindi and Mtwara regions were estimated to be 4–6% and 7–10% respectively in 2003/4 [27] .
The public health system comprises a network of dispensaries, health centres and hospitals offering a varying quality of care [15] . Nearly all (99%) pregnant women attend antenatal care at least once, and around half of women deliver with a skilled attendant [14] .
Between June and October 2007, a survey team of over 200 field staff visited all 243,612 households in the five study districts. Household heads were asked to give their written consent to participate. In a few households (15,823, 7%), nobody could be found on the day of the survey despite repeat visits by interviewers within the day. Over 99% (225,980) agreed to take part. Female participants age 13–49 who had had a live birth in the year before the survey were then separately asked for written consent to participate and were asked questions relating to use of antenatal care, intrapartum care (such as place of childbirth and birth attendant) and postpartum care including essential newborn care indicators, for the most recent birth. Some questions were only asked to women who had had a non-facility delivery.
The questionnaire was administered in Swahili using handheld computers (personal digital assistants or PDA) to capture responses [28] (link). Standard range, consistency and completeness checks were carried out in the field. Analysis was conducted in Stata version 10 [29] .

In this study, data were obtained from institutions and previous studies. The number of FL cases in Taiwan between 2008–2019 was obtained from the Cancer Registry Annual Report of the Health Promotion Administration, Ministry of Health and Welfare, Taiwan [20 ]. The annual population size for calculating incidence was obtained from the Department of Household Registration, Ministry of the Interior, Taiwan [21 ]. These annual reports were based on the Taiwan Cancer Registry Database (TCRD), a high-quality database from a nationwide population-based cancer registry system. In terms of the quality indicators of the registry, the completeness rates ranged from 91.3% in 2001 to 98.3% in 2019, the percentage of death certificate–only cases in all cancer cases (DCO%) decreased from 2.6% in 2003 to 0.7% in 2019, while the percentage of morphological verification (MV%) increased from 87.1% in 2003 to 93.5% in 2019 [15 (link),22 ,23 (link)].
Cases of patients with FL were identified using the International Classification of Disease for Oncology, Third Edition (ICD-O-3; Histology codes: 9690, 9691, 9695, and 9698) [20 ,24 ].
Age-standardized incidence rates (ASRs) and male-to-female incidence rate ratios (M/F IRRs) were calculated. ASR was age-adjusted to the 2000 world standard population as defined by the World Health Organization [25 ]. The temporal trends for the incidence of both sexes were described using the annual percent change (APC) calculated using the Joinpoint Regression Program, Version 4.9.1.0 (NCI Statistical Methodology and Applications Branch, Bethesda, MD, USA) [26 ]. The APCs were estimated by observing the changes in the trend on a log scale and assuming constant variance.
We further combined the data, based on the TCRD, in Taiwan between 2002–2007 as reported by Ko et al. [15 (link)] and compared the ASRs with those reported in Japan and South Korea. Japanese data were retrieved from Chihara et al. and the National Cancer Center, Japan, both of which are population-based cancer registry data [12 (link),27 ]. Korean data were obtained from Lee et al. and Kim et al.; the data were from the Korea Central Cancer Registry, (a hospital-based nationwide cancer registry) and from the National Health Information Database, (a public database that covered the entire Korean population), respectively [2 (link),13 (link)]. Based on the ASRs provided in these reports, we computed the APCs for the Japanese and Korean population.
An independent two-sided t-test was used to determine whether APC was statistically significant from zero. A p-value < 0.05 was considered statistically significant. Incidence rate ratios (IRRs) were calculated using the numbers of FL cases for each area and the age-specific population structure for each year. Statistical significance in difference between IRRs was determined whether the 95% confidence intervals (CIs) overlap between IRRs or not.

This study was performed as part of the Prevention of REnal and Vascular ENd-stage Disease (PREVEND) cohort study, which is a large-scale, prospective population-based cohort study that commenced in 1997 in Groningen, the Netherlands [17 (link)]. The PREVEND study was primarily aimed to study the utility of urinary albumin excretion as indicator of the future occurrence of renal and cardiovascular diseases. The PREVEND study comprises data on a wealth of parameters that are relevant to cardiorenal diseases. In the period from 1997–1998, 85,421 inhabitants of the city of Groningen aged 28–75 years were contacted and requested to complete a short questionnaire asking information on demographics and history of cardiovascular diseases, as well as to send in a first morning void sample. A total of 40,856 individuals (47.8%) responded, from which 7786 individuals with urinary albumin concentrations (UAC) > 10 mg/L and a randomly selected control group of 3395 individuals with UAC < 10 mg/L were invited to participate in subsequent study screening investigations at the outpatient research clinic of the University Medical Center Groningen (UMCG). This screening program was completed by 8592 participants (n = 6000 with UAC > 10 mg/L and n = 2592 with UAC < 10 mg/L), which together formed the total study cohort. In the period of 2001–2003, a second round of study investigations was organized aiming to collect additional data and biomaterials (e.g., blood, urine) from 6894 of these participants. This second study round served as the baseline for the present study. From this cohort of participants, patients with established CKD defined as having an estimated glomerular filtration rate (eGFR) < 60 mL/min/1.73 m² (n = 1082) or unknown CKD status (n = 337) were excluded. Furthermore, participants in whom plasma NGAL levels could not be determined (n = 815) due to either missing samples or insufficient sample volumes) were excluded. This resulted in a final sample size of n = 4660 participants for analysis with a study follow-up that ended on 1 January 2011. The PREVEND study was approved by the Institutional Review Board of the UMCG (full name in Dutch: “Medisch Ethische Toetsingscommissie”, abbreviated as “METc”, IRB no. 01/139). All participants provided written informed consent for study participation. The study was conducted according to the principles of the Declaration of Helsinki. The study reporting was in accordance with the EQUATOR guideline: the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) [18 (link)].