Cost-Effectiveness of Inotuzumab Ozogamicin Compared to Standard of Care Chemotherapy for Treating Relapsed or Refractory Acute Lymphoblastic Leukaemia Patients in Norway and Sweden.

OBJECTIVE: The aim was to estimate the cost-effectiveness of inotuzumab ozogamicin (InO) versus standard of care chemotherapy (SoC) for adults with relapsed or refractory B cell acute lymphoblastic leukaemia (R/R ALL) in Sweden and Norway, and compare this to evaluations made by the health technology assessment (HTA) authorities Tandvårds- och läkemedelsförmånsverket (TLV) and the Norwegian Medicines Agency (NoMA). MATERIALS AND METHODS: A partitioned survival model was developed to determine incremental cost-effectiveness ratios (ICERs) for InO versus SoC. Parametric survival models were fit to overall survival and progression-free survival Kaplan-Meier data from the INO-VATE ALL phase III trial. Two base cases were run using (1) Swedish and (2) Norwegian inputs (costs and discount rates). Core clinical inputs and utilities did not differ between countries. Analyses were then conducted to reflect the preferred assumptions of TLV and NoMA. Univariate and multivariate sensitivity analyses were performed. RESULTS: The base case deterministic ICERs for InO versus SoC were €16,219/quality-adjusted life years (QALY) in Sweden (probabilistic €19,415) and €44,405/QALY in Norway (probabilistic €47,305). The ICERs using our model but applying the preferred assumptions of TLV or NoMA were €74,061/QALY (probabilistic €77,484) and €59,391/QALY (probabilistic €63,632), respectively. Differences between our base cases and the ICERs with TLV and NoMA settings were mainly explained by the exclusion of productivity costs and use of pooled post-haematopoietic stem-cell transplant (post-HSCT) survival in Sweden and use of higher HSCT costs in Norway. All ICERs remained below the approximated willingness-to-pay thresholds. The probability of InO being cost-effective ranged from 77 to 99% versus SoC. CONCLUSIONS: InO can likely be considered cost-effective versus SoC under our and the HTA-preferred settings.

European consensus statement on essential colposcopy.

This European consensus statement on essential colposcopy provides standards for the general colposcopist seeing women referred for colposcopy with an abnormal cervical screening test (including cytology and HPV tests) or with a clinically suspicious cervix. The article gives guidance regarding the aims and conduct of colposcopy. Recommendations are provided on colposcopy technique, the management of common colposcopy issues, treatment and follow-up of after treatment of CIN or early stage cervical. Colposcopists should make an informed decision on the management of each individual that is referred and organize appropriate follow-up. Cervical cancer is still a major health issue and the quality of care can only improve if there is a structured guidance for women with an abnormal smear or suspicious cervix.

Incidence of lichen sclerosus and subsequent causes of death: a nationwide Finnish register study.

OBJECTIVE: To assess the incidence of lichen sclerosus (LS) in women and the all-cause and cause-specific mortality of women with LS. DESIGN: Population-based descriptive study. SETTING: Finland. POPULATION: All Finnish women, including 7790 women diagnosed with LS during the period 1969-2012. METHODS: Information gathered from the Finnish Hospital Discharge Register on women with LS was combined with dates and causes of death from Statistics Finland and the Finnish Cancer Registry. Population statistics are from Statistics Finland. MAIN OUTCOME MEASURES: Crude and age-adjusted incidence rates of LS and standardised mortality ratios (SMRs). RESULTS: The incidence rate of LS adjusted for age (European Standard Population) increased from 14 per 100 000 woman-years in 2003 to 22 per 100 000 woman-years in 2010-2012. The age-specific incidence rate was highest in postmenopausal women (24-53 per 100 000) but was also elevated in girls aged 5-9 years (seven per 100 000). The all-cause mortality of women with LS was lower than in the general female population (SMR 0.84, 95% CI 0.78-0.90), mostly as a result of decreased mortality from circulatory diseases (SMR 0.80, 95% CI 0.72-0.89) and dementia and Alzheimer's disease (SMR 0.75, 95% CI 0.62-0.88). The cancer mortality equalled that of the population, but the vulvar cancer mortality was increased (SMR 28.1, 95% CI 19.3-39.4). CONCLUSIONS: Lichen sclerosus is a common disease of elderly women. The overall mortality is decreased whereas the mortality as a result of vulvar cancer is increased. TWEETABLE ABSTRACT: The likelihood of getting LS by age 80 years is 1.6%. The mortality of women with LS is reduced compared with that of the population.

Patterns of African and Asian admixture in the Afrikaner population of South Africa.

BACKGROUND: The Afrikaner population of South Africa is the descendants of European colonists who started to colonize the Cape of Good Hope in the 1600s. In the early days of the colony, mixed unions between European males and non-European females gave rise to admixed children who later became incorporated into either the Afrikaner or the Coloured populations of South Africa. Differences in ancestry, social class, culture, sex ratio and geographic structure led to distinct and characteristic admixture patterns in the Afrikaner and Coloured populations. The Afrikaner population has a predominant European composition, whereas the Coloured population has more diverse ancestries. Genealogical records previously estimated the contribution of non-Europeans into the Afrikaners to be between 5.5 and 7.2%. RESULTS: To investigate the genetic ancestry of the Afrikaner population today (11-13 generations after initial colonization), we genotyped approximately five million genome-wide markers in 77 Afrikaner individuals and compared their genotypes to populations across the world to determine parental source populations and admixture proportions. We found that the majority of Afrikaner ancestry (average 95.3%) came from European populations (specifically northwestern European populations), but that almost all Afrikaners had admixture from non-Europeans. The non-European admixture originated mostly from people who were brought to South Africa as slaves and, to a lesser extent, from local Khoe-San groups. Furthermore, despite a potentially small founding population, there is no sign of a recent bottleneck in the Afrikaner compared to other European populations. Admixture amongst diverse groups from Europe and elsewhere during early colonial times might have counterbalanced the effects of a small founding population. CONCLUSIONS: While Afrikaners have an ancestry predominantly from northwestern Europe, non-European admixture signals are ubiquitous in the Afrikaner population. Interesting patterns and similarities could be observed between genealogical predictions and our genetic inferences. Afrikaners today have comparable inbreeding levels to current-day European populations.

BedMachine v3: Complete Bed Topography and Ocean Bathymetry Mapping of Greenland From Multibeam Echo Sounding Combined With Mass Conservation.

Greenland's bed topography is a primary control on ice flow, grounding line migration, calving dynamics, and subglacial drainage. Moreover, fjord bathymetry regulates the penetration of warm Atlantic water (AW) that rapidly melts and undercuts Greenland's marine-terminating glaciers. Here we present a new compilation of Greenland bed topography that assimilates seafloor bathymetry and ice thickness data through a mass conservation approach. A new 150 m horizontal resolution bed topography/bathymetric map of Greenland is constructed with seamless transitions at the ice/ocean interface, yielding major improvements over previous data sets, particularly in the marine-terminating sectors of northwest and southeast Greenland. Our map reveals that the total sea level potential of the Greenland ice sheet is 7.42 ± 0.05 m, which is 7 cm greater than previous estimates. Furthermore, it explains recent calving front response of numerous outlet glaciers and reveals new pathways by which AW can access glaciers with marine-based basins, thereby highlighting sectors of Greenland that are most vulnerable to future oceanic forcing.

Massive remobilization of permafrost carbon during post-glacial warming.

Recent hypotheses, based on atmospheric records and models, suggest that permafrost carbon (PF-C) accumulated during the last glaciation may have been an important source for the atmospheric CO2 rise during post-glacial warming. However, direct physical indications for such PF-C release have so far been absent. Here we use the Laptev Sea (Arctic Ocean) as an archive to investigate PF-C destabilization during the last glacial-interglacial period. Our results show evidence for massive supply of PF-C from Siberian soils as a result of severe active layer deepening in response to the warming. Thawing of PF-C must also have brought about an enhanced organic matter respiration and, thus, these findings suggest that PF-C may indeed have been an important source of CO2 across the extensive permafrost domain. The results challenge current paradigms on the post-glacial CO2 rise and, at the same time, serve as a harbinger for possible consequences of the present-day warming of PF-C soils.

The mitogenome of a 35,000-year-old Homo sapiens from Europe supports a Palaeolithic back-migration to Africa.

After the dispersal of modern humans (Homo sapiens) Out of Africa, hominins with a similar morphology to that of present-day humans initiated the gradual demographic expansion into Eurasia. The mitogenome (33-fold coverage) of the Pestera Muierii 1 individual (PM1) from Romania (35 ky cal BP) we present in this article corresponds fully to Homo sapiens, whilst exhibiting a mosaic of morphological features related to both modern humans and Neandertals. We have identified the PM1 mitogenome as a basal haplogroup U6*, not previously found in any ancient or present-day humans. The derived U6 haplotypes are predominantly found in present-day North-Western African populations. Concomitantly, those found in Europe have been attributed to recent gene-flow from North Africa. The presence of the basal haplogroup U6* in South East Europe (Romania) at 35 ky BP confirms a Eurasian origin of the U6 mitochondrial lineage. Consequently, we propose that the PM1 lineage is an offshoot to South East Europe that can be traced to the Early Upper Paleolithic back migration from Western Asia to North Africa, during which the U6 lineage diversified, until the emergence of the present-day U6 African lineages.

Abnormally invasive placenta-prevalence, risk factors and antenatal suspicion: results from a large population-based pregnancy cohort study in the Nordic countries.

OBJECTIVE: The objective was to investigate prevalence, estimate risk factors, and antenatal suspicion of abnormally invasive placenta (AIP) associated with laparotomy in women in the Nordic countries. DESIGN: Population-based cohort study. SETTING AND POPULATION: A 3-year Nordic collaboration among obstetricians to identify and report on uterine rupture, peripartum hysterectomy, excessive blood loss, and AIP from 2009 to 2012 The Nordic Obstetric Surveillance Study (NOSS). METHODS: In the NOSS study, clinicians reported AIP cases from maternity wards and the data were validated against National health registries. MAIN OUTCOME MEASURES: Prevalence, risk factors, antenatal suspicion, birth complications, and risk estimations using aggregated national data. RESULTS: A total of 205 cases of AIP in association with laparotomy were identified, representing 3.4 per 10 000 deliveries. The single most important risk factor, which was reported in 49% of all cases of AIP, was placenta praevia. The risk of AIP increased seven-fold after one prior caesarean section (CS) to 56-fold after three or more CS. Prior postpartum haemorrhage was associated with six-fold increased risk of AIP (95% confidence interval 3.7-10.9). Approximately 70% of all cases were not diagnosed antepartum. Of these, 39% had prior CS and 33% had placenta praevia. CONCLUSION: Our findings indicate that a lower CS rate in the population may be the most effective way to lower the incidence of AIP. Focused ultrasound assessment of women at high risk will likely strengthen antenatal suspicion. Prior PPH is a novel risk factor associated with an increased prevalence of AIP. TWEETABLE ABSTRACT: An ultrasound assessment in women with placenta praevia or prior CS may double the awareness for AIP.

Determining obstetric patient safety indicators: the differences in neonatal outcome measures between different-sized delivery units.

OBJECTIVE: To study the differences in neonatal outcome and treatment measures in Finnish obstetric units. DESIGN: A registry study with Medical Birth Register data. SETTING AND POPULATION: All births (n = 2 94 726) in Finland from 2006 to 2010 with a focus on term, singleton non-university deliveries. METHODS: All 34 delivery units were grouped into small (below 1000), mid-sized (1000-2999) and large (3000 or more) units, and the adverse outcome rates in neonates were compared using logistic regression. MAIN OUTCOME MEASURES: Early neonatal deaths, stillbirths, Apgar scores, arterial cord pH, Erb's paralysis, respirator treatment, the proportion of post-term deliveries (gestational age beyond 42 weeks) and the proportion of newborns still hospitalised 7 days after delivery. RESULTS: From an analysis of term, singleton non-university deliveries, the early neonatal mortality was significantly higher in the small relative to the mid-sized delivery units [odds ratio (OR), 2.07; 95% confidence interval (CI), 1.19-3.60]. The rate of Erb's paralysis was lowest in the large units (OR, 0.65; 95% CI, 0.50-0.84). The use of a respirator was more than two-fold more common in large relative to mid-sized units (OR, 2.38; 95% CI, 2.00-2.83). The proportion of post-term deliveries was highest in the large units (OR, 1.36; 95% CI, 1.31-1.42), where a significantly higher percentage of post-term newborns were still hospitalised after 7 days (OR, 1.50; 95% CI, 1.19-1.89). CONCLUSIONS: There are significant differences in several neonatal indicators dependent on the hospital size. An international consensus is needed on which indicators should be used.

Treatment and overall survival in renal cell carcinoma: a Swedish population-based study (2000-2008).

BACKGROUND: This retrospective register study assessed overall survival (OS) and influential factors on OS in Swedish renal cell carcinoma (RCC) patients. METHODS: Using three merged national health registers, Cox proportional-hazards analysis was conducted and, in three models, it was used to assess the impact of cytokine (interferon-α and tyrosine kinase inhibitor (TKI; sunitinib or sorafenib) treatment on OS in metastatic (m)RCC. RESULTS: From 2000 to 2008, 8009 patients were diagnosed with RCC and 2753 with mRCC (2002-2008). Median OS in RCC patients diagnosed from 2006 to 2008 compared with 2000-2005 was not reached vs 47.9 months (P<0.001), and in mRCC patients diagnosed from 2006 to 2008 compared with 2002-2005, was 12.4 vs 9.6 months, respectively (P=0.004). Factors associated with significantly improved OS in RCC were female gender, lower age, and previous nephrectomy, and, in mRCC female gender, previous nephrectomy, and any TKI prescription (Model 1: median-adjusted OS, 19.4 months (TKI patients) vs 9.7 months (non-TKI patients); hazard ratio, 0.621; P<0.001). CONCLUSION: OS was improved in Swedish patients diagnosed with RCC and mRCC in the period 2006-2008 compared with 2000-2005 (RCC) and 2002-2005 (mRCC). Although multifactorial in origin, results suggest that increased nephrectomy rates and the use of TKIs contributed to the improvement seen in mRCC patients.

Inferring population size changes with sequence and SNP data: lessons from human bottlenecks.

Reconstructing historical variation of population size from sequence and single-nucleotide polymorphism (SNP) data is valuable for understanding the evolutionary history of species. Changes in the population size of humans have been thoroughly investigated, and we review different methodologies of demographic reconstruction, specifically focusing on human bottlenecks. In addition to the classical approaches based on the site-frequency spectrum (SFS) or based on linkage disequilibrium, we also review more recent approaches that utilize atypical shared genomic fragments, such as identical by descent or homozygous segments between or within individuals. Compared with methods based on the SFS, these methods are well suited for detecting recent bottlenecks. In general, all these various methods suffer from bias and dependencies on confounding factors such as population structure or poor specification of the mutational and recombination processes, which can affect the demographic reconstruction. With the exception of SFS-based methods, the effects of confounding factors on the inference methods remain poorly investigated. We conclude that an important step when investigating population size changes rests on validating the demographic model by investigating to what extent the fitted demographic model can reproduce the main features of the polymorphism data.

Colposcopy referral rate can be reduced by high-risk human papillomavirus triage in the management of recurrent atypical squamous cells of undetermined significance or low-grade squamous intraepithelial lesion cytology in Finland.

The aim of this study was to establish whether a combination of high-risk human papillomavirus (hrHPV) testing and cervical cytology could reduce colposcopy referral among women with atypical squamous cells of undetermined significance (ASCUS) or low-grade squamous intraepithelial lesion cytology. We randomized 598 women in the Helsinki area, Finland into three study groups. Different strategies of hrHPV testing, cytology and colposcopy with biopsy were used; subsequent hrHPV test results and cytological findings were compared with histology. The rates of hrHPV positivity and CIN2+ were compared. In total, 62.5% of all samples were hrHPV-positive. Altogether 45 (12.7%) CIN2 or worse (CIN2+) lesions were found in study groups A and B. Among hrHPV-positive women the rate of CIN2+ was 19.0% (n = 43), in contrast with 1.6% (n = 2) among hrHPV-negative women (relative risk = 12.2, 95% confidence interval [CI] 3.6-81.1, P < 0.001). Among all hrHPV-negative women whose cytological findings were normal or ASCUS, dysplastic lesions were uncommon (n = 4/119, 3.4%), and all were CIN1. If these women had not been referred to colposcopy, the number of colposcopies would have been reduced by 33.6%. We conclude that hrHPV testing combined with repeat cervical cytology had a high negative predictive value in patients with recurrent low-grade cervical cytology. This could reduce the referral rate to colposcopy without jeopardizing patient safety.

What is a 'secure base' when death is approaching? A study applying attachment theory to adult patients' and family members' experiences of palliative home care.

OBJECTIVE: Attachment theory has received much interest lately in relation to how adults cope with stress and severe illness. The aim of this study was using the experiences of patients and family members to explore palliative home care as a 'secure base' (a central concept within the theory). METHODS: Twelve patients and 14 family members were interviewed during ongoing palliative home care. The interviews were analysed with deductive qualitative content analysis. RESULTS: Informants expressed the relevance of sensing security during palliative home care because death and dying were threats that contributed to vulnerability. Palliative home care could foster a feeling of security and provide a secure base. This was facilitated when informants had trust in staff (e.g. due to availability and competence in providing symptom relief), felt recognised as individuals and welcomed to contact the team in times of needs. Being comfortable, informed and having an everyday life also contributed to a perception of palliative home care as a secure base. Family members stressed the importance of being relieved from responsibilities that were too heavy. The underlying meanings of experiencing palliative home care as a secure base involved gaining a sense of control and of inner peace, perceiving that despite a demanding and changed life situation, one could continue partially being oneself and having something to hope for, even if this no longer concerned cure for the ill person. CONCLUSIONS: Important aspects of palliative home care as providing a secure base were identified and these have implications for clinical practice.

Long-term mortality in women treated for cervical intraepithelial neoplasia.

OBJECTIVE: The objective of this study was to study whether women surgically treated for cervical intraepithelial neoplasia (CIN) have increased mortality later in life. We also wanted to study whether pregnancy beyond 22 weeks post-treatment affects the risk. DESIGN: Register-based retrospective cohort study from Finland. SETTING: National data of the Hospital Discharge Register and the Cause-of-Death Register during 1986-2003. POPULATION: A total of 25 827 women who had surgical treatment for CIN during 1986-2003. METHODS: We calculated standardised mortality ratios (SMRs) by dividing the numbers of observed deaths (until 31 December 2006) by the numbers of expected deaths. MAIN OUTCOME MEASURES: SMRs for different causes-of-death groups. RESULTS: The overall mortality increased by 17% after treatment for CIN, including increased risk of dying from all diseases and medical conditions (SMR 1.13, 95% CI 1.01-1.26), cancers (SMR 1.09, 95% CI 0.91-1.27) and injury deaths (SMR 1.31, 95% CI 1.03-1.58). As expected, the mortality from cervical cancer was high (SMR 7.69, 95% CI 4.23-11.15). Women who had delivered post-treatment tended to have decreased overall mortality (SMR 0.78, 95% CI 0.52-1.04) and decreased disease mortality (SMR 0.63, 95% CI 0.37-0.90). However, the mortality rate was significantly increased for women who had subsequent preterm delivery (SMR 2.51, 95% CI 1.24-3.78). In this subgroup, there was a tendency of increased mortality from diseases of the circulatory system, alcohol-related causes and injury deaths. CONCLUSIONS: Mortality rate was increased after surgical treatment for CIN. However, women who had delivered post-treatment had decreased overall disease mortality rate. Subsequent preterm delivery may be a risk marker for increased long-term mortality.

Using population mixtures to optimize the utility of genomic databases: linkage disequilibrium and association study design in India.

When performing association studies in populations that have not been the focus of large-scale investigations of haplotype variation, it is often helpful to rely on genomic databases in other populations for study design and analysis - such as in the selection of tag SNPs and in the imputation of missing genotypes. One way of improving the use of these databases is to rely on a mixture of database samples that is similar to the population of interest, rather than using the single most similar database sample. We demonstrate the effectiveness of the mixture approach in the application of African, European, and East Asian HapMap samples for tag SNP selection in populations from India, a genetically intermediate region underrepresented in genomic studies of haplotype variation.

The incidence of preterm deliveries decreases in Finland.

OBJECTIVE: We examined the trends and risk factors of preterm delivery. DESIGN: Register-based retrospective cohort study from Finland. SETTING: National Medical Birth Register data during 1987-2005. POPULATION: The study population consisted of 1 137 515 deliveries, of which 59 025 were preterm (5.2%). METHODS: We calculated the population attributable risks for using the risk factor prevalence rates in the population. We further calculated odds ratios with 95% CI by multivariate logistic regression to adjust for confounders. MAIN OUTCOME MEASURES: Preterm delivery rate subclassified into moderately preterm (32-36 weeks), very preterm (28-31 weeks) and extremely preterm (less than 28 weeks). RESULTS; Preterm delivery rates increased from 5.1% in the late 1980s to 5.4% in the late 1990s but then decreased to 5.2% for 2001-05. The proportion of extremely preterm deliveries decreased substantially by 12% (P < 0.01). The greatest risk factors were multiplicity (OR 13.72, 95% CI 13.26-14.19), followed by elective delivery (OR 1.86, 95% CI 1.82-1.89), primiparity (OR 1.47, 95% CI 1.45-1.50), in vitro fertilisation treatment (OR 1.39, 95% CI 1.31-1.47), maternal smoking (OR 1.31, 95% CI 1.29-1.34) and advanced maternal age (OR 1.02, 95% CI 1.02-1.03 for each additional year of age). Prematurity rates decreased by 1.8% after adjusting for risk variables. CONCLUSIONS: The rate of preterm delivery has not increased from 1987 to 2005 in Finland, while the risk for extremely preterm delivery has decreased. This finding is in contrast with recent trends in other countries.

The evolutionary history of the common chloroplast genome of Arabidopsis thaliana and A. suecica.

The evolutionary history of the common chloroplast (cp) genome of the allotetraploid Arabidopsis suecica and its maternal parent A. thaliana was investigated by sequencing 50 fragments of cpDNA, resulting in 98 polymorphic sites. The variation in the A. suecica sample was small, in contrast to that of the A. thaliana sample. The time to the most recent common ancestor (T(MRCA)) of the A. suecica cp genome alone was estimated to be about one 37th of the T(MRCA) of both the A. thaliana and A. suecica cp genomes. This corresponds to A. suecica having a MRCA between 10 000 and 50 000 years ago, suggesting that the entire species originated during, or before, this period of time, although the estimates are sensitive to assumptions made about population size and mutation rate. The data was also consistent with the hypothesis of A. suecica being of single origin. Isolation-by-distance and population structure in A. thaliana depended upon the geographical scale analysed; isolation-by-distance was found to be weak on the global scale but locally pronounced. Within the genealogical cp tree of A. thaliana, there were indications that the root of the A. suecica species is located among accessions of A. thaliana that come primarily from central Europe. Selective neutrality of the cp genome could not be rejected, despite the fact that it contains several completely linked protein-coding genes.

Enhanced ice sheet growth in Eurasia owing to adjacent ice-dammed lakes.

Large proglacial lakes cool regional summer climate because of their large heat capacity, and have been shown to modify precipitation through mesoscale atmospheric feedbacks, as in the case of Lake Agassiz. Several large ice-dammed lakes, with a combined area twice that of the Caspian Sea, were formed in northern Eurasia about 90,000 years ago, during the last glacial period when an ice sheet centred over the Barents and Kara seas blocked the large northbound Russian rivers. Here we present high-resolution simulations with an atmospheric general circulation model that explicitly simulates the surface mass balance of the ice sheet. We show that the main influence of the Eurasian proglacial lakes was a significant reduction of ice sheet melting at the southern margin of the Barents-Kara ice sheet through strong regional summer cooling over large parts of Russia. In our simulations, the summer melt reduction clearly outweighs lake-induced decreases in moisture and hence snowfall, such as has been reported earlier for Lake Agassiz. We conclude that the summer cooling mechanism from proglacial lakes accelerated ice sheet growth and delayed ice sheet decay in Eurasia and probably also in North America.

Chloroplast DNA indicates a single origin of the allotetraploid Arabidopsis suecica.

DNA sequencing was performed on up to 12 chloroplast DNA regions [giving a total of 4288 base pairs (bp) in length] from the allopolyploid Arabidopsis suecica (48 accessions) and its two parental species, A. thaliana (25 accessions) and A. arenosa (seven accessions). Arabidopsis suecica was identical to A. thaliana at all 93 sites where A. thaliana and A. arenosa differed, thus showing that A. thaliana is the maternal parent of A. suecica. Under the assumption that A. thaliana and A. arenosa separated 5 million years ago, we estimated a substitution rate of 2.9 x 10(-9) per site per year in noncoding single copy sequence. Within A. thaliana we found 12 substitution (single bp) and eight insertion/deletion (indel) polymorphisms, separating the 25 accessions into 15 haplotypes. Eight of the A. thaliana accessions from central Sweden formed one cluster, which was separated from a cluster consisting of central European and extreme southern Swedish accessions. This latter cluster also included the A. suecica accessions, which were all identical except for one 5 bp indel. We interpret this low level of variation as a strong indication that A. suecica effectively has a single origin, which we dated at 20 000 years ago or more.