Recent Submissions

  • Tekoniemi, Timo Tapani (Yhteiskunnallisen ja kulttuurisen eläintutkimuksen seura, 2017)
    Gilgameš-eepos oli yksi muinaisen Mesopotamian tärkeimmistä kirjallisista teoksista, ja sitä voidaan pitää keskeisenä läpileikkauksena muinaiseen mesopotamialaiseen ajatteluun. Tässä artikkelissa käydään läpi eepoksen viittaukset eläimiin ja niiden pohjalta selvitetään sitä, millainen rooli eläimillä oli teoksen kirjoittajien ajattelussa. Artikkeli osoittaa myös, että eepoksen kielellinen ilmaisuvoima kytkeytyy tiiviisti sen laajaan eläinkuvastoon. Joissain kohdissa, joissa muinainen teksti on osittain turmeltunut, voidaan teoksen eläinkuvaa tutkimalla jopa saada selvyyttä tekstin alkuperäisiin sanamuotoihin. Eepoksen eläimiin liittyvä kuvasto on erittäin runsasta ja heijastaa eläinten suurta arvoa ajan ihmisille, joille tiivis yhteiselo eri eläinlajien kanssa oli välttämättömyys. Eepos ei kuitenkaan vain kuvaile eläimiä osana ihmisten arkea vaan heijastaa myös laajemmin aikalaisten eläinkuvaa sekä ymmärrystä eri lajien ominaispiirteistäja niihin kohdistetuista asenteista. Eläimet eivät jää teoksessa pelkiksi sivustakatsojiksi, vaan jotkin lajit saavat narratologisesti tärkeän ja aktiivisen roolin. Muinaisen Mesopotamian eläinkuvan tarkempi tarkastelu puolestaan auttaa löytämään teoksesta merkityksiä, jotka ajan kulttuuria ja eläinkäsityksiä tuntemattomalle eivät muutoin avaudu. Eräs eepoksen tärkeimmistä teemoista on rajankäynti ihmisyyden ja jumaluuden välillä, mutta eepos tarjoaa näkymän myös mesopotamialaiseen käsitykseen ihmisen ja eläimen käsitetyistä eroista. Gilgamešin kumppani, villimies Enkidu, herättää kysymyksen siitä, miten muinaiset mesopotamialaiset ymmärsivät ihmistä ja eläintä erottavat piirteet. Voiko eron nähdä olleen tiukan binäärinen? Vai tehtiinkö tarkkaa eroa käytännössä lainkaan?
  • Wolin, Annika; Lahtela, Laura Elisa; Anttila, Verneri; Petrek, Martin; Grunewald, Johan; van Moorsel, Coline H. M.; Eklund, Anders; Grutters, Jan C.; Kolek, Vitezslav; Mrazek, Frantisek; Kishore, Amit; Padyukov, Leonid; Pietinalho, Anne; Ronninger, Marcus; Seppanen, Mikko; Selroos, Olof; Lokki, Marja-Liisa (Frontiers Media S.A., 2017)
    Sarcoidosis is a multiorgan inflammatory disorder with heritability estimates up to 66%. Previous studies have shown the major histocompatibility complex (MHC) region to be associated with sarcoidosis, suggesting a functional role for antigen-presenting molecules and immune mediators in the disease pathogenesis. To detect variants predisposing to sarcoidosis and to identify genetic differences between patient subgroups, we studied four genes in the MHC Class III region (LTA, TNF, AGER, BTNL2) and HLA-DRA with tag-SNPs and their relation to HLA-DRB1 alleles. We present results from a joint analysis of four study populations (Finnish, Swedish, Dutch, and Czech). Patients with sarcoidosis (n = 805) were further subdivided based on the disease activity and the presence of Lofgren's syndrome. In a joint analysis, seven SNPs were associated with non-Lofgren sarcoidosis (NL; the strongest association with rs3177928, P = 1.79E-07, OR = 1.9) and eight with Lofgren's syndrome [ Lofgren syndrome (LS); the strongest association with rs3129843, P = 3.44E-12, OR = 3.4] when compared with healthy controls (n = 870). Five SNPs were associated with sarcoidosis disease course (the strongest association with rs3177928, P = 0.003, OR = 1.9). The high linkage disequilibrium (LD) between SNPs and an HLA-DRB1 challenged the result interpretation. When the SNPs and HLA-DRB1 alleles were analyzed together, independent association was observed for four SNPs in the HLA-DRA/BTNL2 region: rs3135365 (NL; P = 0.015), rs3177928 (NL; P <0.001), rs6937545 (LS; P = 0.012), and rs5007259 (disease activity; P = 0.002). These SNPs act as expression quantitative trait loci (eQTL) for HLA-DRB1 and/or HLA-DRB5. In conclusion, we found novel SNPs in BTNL2 and HLA-DRA regions associating with sarcoidosis. Our finding further establishes that polymorphisms in the HLA-DRA and BTNL2 have a role in sarcoidosis susceptibility. This multi-population study demonstrates that at least a part of these associations are HLA-DRB1 independent (e.g., not due to LD) and shared across ancestral origins. The variants that were independent of HLA-DRB1 associations acted as eQTL for HLA-DRB1 and/or -DRB5, suggesting a role in regulating gene expression.
  • Viranta, Suvi; Atickem, Anagaw; Werdelin, Lars; Stenseth, Nils Chr. (BioMed Central, 2017)
    Abstract Background The African wolf, for which we herein recognise Canis lupaster Hemprich and Ehrenberg, 1832 (Symbolae Physicae quae ex Itinere Africam Borealem er Asoam Occidentalem Decas Secunda. Berlin, 1833) as the valid species name (we consider the older name Canis anthus Cuvier, 1820 [Le Chacal de Sénégal, Femelle. In: Geoffroy St.-Hilaire E, Cuvier F, editors. Histoire Naturelle des Mammifères Paris, A. Belin, 1820] a nomen dubium), is a medium-sized canid with wolf-like characters. Because of phenotypic similarity, specimens of African wolf have long been assigned to golden jackal (Canis aureus Linnaeus, 1758 [Systema Naturae per Regna Tria Naturae, Secundum Classes, Ordines, Genera, Species, cum Characteribus, Differentiis, Synonymis, Locis. Tomus I. Editio decima, reformata, 1758]). Results Here we provide, through rigorous morphological analysis, a species description for this taxonomically overlooked species. Through molecular sequencing we assess its distribution in Africa, which remains uncertain due to confusion regarding possible co-occurrence with the Eurasian golden jackal. Canis lupaster differs from all other Canis spp. including the golden jackal in its cranial morphology, while phylogenetically it shows close affinity to the Holarctic grey wolf (Canis lupus Linnaeus, 1758 [Systema Naturae per Regna Tria Naturae, Secundum Classes, Ordines, Genera, Species, cum Characteribus, Differentiis, Synonymis, Locis. Tomus I. Editio decima, reformata, 1758]). All sequences generated during this study clustered with African wolf specimens, consistent with previous data for the species. Conclusions We suggest that the estimated current geographic range of golden jackal in Africa represents the African wolf range. Further research is needed in eastern Egypt, where a hybrid zone between Eurasian golden jackal and African wolf may exist. Our results highlight the need for improved studies of geographic range and population surveys for the taxon, which is classified as ‘least concern’ by the IUCN due to its erroneous identification as golden jackal. As a species exclusively distributed in Africa, investigations of the biology and threats to African wolf are needed. Keywords African wolf Canidae Canis lupaster Canis aureus Taxonomy Conservation
  • Saraswat, Mayank; Joenvaara, Sakari; Seppanen, Hanna; Mustonen, Harri; Haglund, Caj; Renkonen, Risto (Wiley, 2017)
    Finland ranks sixth among the countries having highest incidence rate of pancreatic cancer with mortality roughly equaling incidence. The average age of diagnosis for pancreatic cancer is 69years in Nordic males, whereas the average age of diagnosis of chronic pancreatitis is 40-50years, however, many cases overlap in age. By radiology, the evaluation of a pancreatic mass, that is, the differential diagnosis between chronic pancreatitis and pancreatic cancer is often difficult. Preoperative needle biopsies are difficult to obtain and are demanding to interpret. New blood based biomarkers are needed. The accuracy of the only established biomarker for pancreatic cancer, CA 19-9 is rather poor in differentiating between benign and malignant mass of the pancreas. In this study, we have performed mass spectrometry analysis (High Definition MSE) of serum samples from patients with chronic pancreatitis (13) and pancreatic cancer (22). We have quantified 291 proteins and performed detailed statistical analysis such as principal component analysis, orthogonal partial least square discriminant analysis and receiver operating curve analysis. The proteomic signature of chronic pancreatitis versus pancreatic cancer samples was able to separate the two groups by multiple statistical techniques. Some of the enriched pathways in the proteomic dataset were LXR/RXR activation, complement and coagulation systems and inflammatory response. We propose that multiple high-confidence biomarker candidates in our pilot study including Inter-alpha-trypsin inhibitor heavy chain H2 (Area under the curve, AUC: 0.947), protein AMBP (AUC: 0.951) and prothrombin (AUC: 0.917), which should be further evaluated in larger patient series as potential new biomarkers for differential diagnosis.
  • Li, Dong; Chang, Xiao; Connolly, John J.; Tian, Lifeng; Liu, Yichuan; Bhoj, Elizabeth J.; Robinson, Nora; Abrams, Debra; Li, Yun R.; Bradfield, Jonathan P.; Kim, Cecilia E.; Li, Jin; Wang, Fengxiang; Snyder, James; Lemma, Maria; Hou, Cuiping; Wei, Zhi; Guo, Yiran; Qiu, Haijun; Mentch, Frank D.; Thomas, Kelly A.; Chiavacci, Rosetta M.; Cone, Roger; Li, Bingshan; Sleiman, Patrick A.; Hakonarson, Hakon; Eating Disorders Working Group of the Psychiatric Genomics Consortium; Raevuori-Helkamaa, Anu; Price Fdn Collaborative Grp (Nature Publishing Group, 2017)
    We conducted a genome-wide association study (GWAS) of anorexia nervosa (AN) using a stringently defined phenotype. Analysis of phenotypic variability led to the identification of a specific genetic risk factor that approached genome-wide significance (rs929626 in EBF1 (Early B-Cell Factor 1); P = 2.04 x 10(-7); OR = 0.7; 95% confidence interval (CI) = 0.61-0.8) with independent replication (P = 0.04), suggesting a variant-mediated dysregulation of leptin signaling may play a role in AN. Multiple SNPs in LD with the variant support the nominal association. This demonstrates that although the clinical and etiologic heterogeneity of AN is universally recognized, further careful sub-typing of cases may provide more precise genomic signals. In this study, through a refinement of the phenotype spectrum of AN, we present a replicable GWAS signal that is nominally associated with AN, highlighting a potentially important candidate locus for further investigation.
  • Ylönen, Irene; Lilja, Johanna; Holopainen, Mika Antero (Informaatiotutkimuksen yhdistys ry., 2017)
  • Wilén, Raine; Holopainen, Mika Antero (Informaatiotutkimuksen yhdistys ry., 2017)
  • Yli-Jyrä, Anssi Mikael (2017)
    NEALT Proceedings Series
    Sequential Constraint Grammar (SCG) (Karlsson, 1990) and its extensions have lacked clear connections to formal language theory. The purpose of this article is to lay a foundation for these connections by simplifying the definition of strings processed by the grammar and by showing that Nonmonotonic SCG is undecidable and that derivations similar to the Generative Phonology exist. The current investigations propose resource bounds that restrict the generative power of SCG to a subset of context sensitive languages and present a strong finite-state condition for grammars as wholes. We show that a grammar is equivalent to a finite-state transducer if it is implemented with a Turing machine that runs in o(n log n) time. This condition opens new finite-state hypotheses and avenues for deeper analysis of SCG instances in the way inspired by Finite-State Phonology.
  • Byars, Sean G.; Huang, Qin Qin; Gray, Lesley-Ann; Bakshi, Andrew; Ripatti, Samuli; Abraham, Gad; Stearns, Stephen C.; Inouye, Michael (PUBLIC LIBRARY OF SCIENCE, 2017)
    Traditional genome-wide scans for positive selection have mainly uncovered selective sweeps associated with monogenic traits. While selection on quantitative traits is much more common, very few signals have been detected because of their polygenic nature. We searched for positive selection signals underlying coronary artery disease (CAD) in worldwide populations, using novel approaches to quantify relationships between polygenic selection signals and CAD genetic risk. We identified new candidate adaptive loci that appear to have been directly modified by disease pressures given their significant associations with CAD genetic risk. These candidates were all uniquely and consistently associated with many different male and female reproductive traits suggesting selection may have also targeted these because of their direct effects on fitness. We found that CAD loci are significantly enriched for lifetime reproductive success relative to the rest of the human genome, with evidence that the relationship between CAD and lifetime reproductive success is antagonistic. This supports the presence of antagonistic-pleiotropic tradeoffs on CAD loci and provides a novel explanation for the maintenance and high prevalence of CAD in modern humans. Lastly, we found that positive selection more often targeted CAD gene regulatory variants using HapMap3 lymphoblastoid cell lines, which further highlights the unique biological significance of candidate adaptive loci underlying CAD. Our study provides a novel approach for detecting selection on polygenic traits and evidence that modern human genomes have evolved in response to CAD-induced selection pressures and other early-life traits sharing pleiotropic links with CAD.
  • Hijazi, Ziad; Lindahl, Bertil; Oldgren, Jonas; Andersson, Ulrika; Lindback, Johan; Granger, Christopher B.; Alexander, John H.; Gersh, Bernard J.; Hanna, Michael; Harjola, Veli-Pekka; Hylek, Elaine M.; Lopes, Renato D.; Siegbahn, Agneta; Wallentin, Lars (Wiley, 2017)
    Background--Cardiac biomarkers are independent risk markers in atrial fibrillation, and the novel biomarker-based ABC stroke score (age, biomarkers, and clinical history of prior stroke) was recently shown to improve the prediction of stroke risk in patients with atrial fibrillation. Our aim was to investigate the short-term variability of the cardiac biomarkers and evaluate whether the ABC stroke risk score provides a stable short- term risk estimate. Methods and Results--According to the study protocol, samples were obtained at entry and also at 2 months in 4796 patients with atrial fibrillation followed for a median of 1.8 years in the ARISTOTLE (Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation) trial. Cardiac troponin I, cardiac troponin T, and N-terminal pro-B-type natriuretic peptide were measured with high-sensitivity immunoassays. Associations with outcomes were evaluated by Cox regression. C indices and calibration plots were used to evaluate the ABC stroke score at 2 months. The average changes in biomarker levels during 2 months were small ( median change cardiac troponin T +2.8%, troponin I +2.0%, and N-terminal pro-B-type natriuretic peptide +13.5%) and within-subject correlation was high ( all >= 0.82). Repeated measurement of cardiac biomarkers provided some incremental prognostic value for mortality but not for stroke when combined with clinical risk factors and baseline levels of the biomarkers. Based on 8702 person-years of follow-up and 96 stroke/systemic embolic events, the ABC stroke score at 2 months achieved a similar C index of 0.70 (95% CI, 0.65-0.76) as compared with 0.70 (95% CI, 0.65-0.75) at baseline. The ABC stroke score remained well calibrated using predefined risk classes. Conclusions--In patients with stable atrial fibrillation, the variability of the cardiac biomarkers and the biomarker- based ABC stroke score during 2 months are small. The prognostic information by the ABC stroke score remains consistent and well calibrated with similar good predictive performance if patients are retested after 2 months. Clinical Trial Registration --URL: Unique identifier: NCT00412984.
  • Marques, Francine Z.; Prestes, Priscilla R.; Byars, Sean G.; Ritchie, Scott C.; Wurtz, Peter; Patel, Sheila K.; Booth, Scott A.; Rana, Indrajeetsinh; Minoda, Yosuke; Berzins, Stuart P.; Curl, Claire L.; Bell, James R.; Wai, Bryan; Srivastava, Piyush M.; Kangas, Antti J.; Soininen, Pasi; Ruohonen, Saku; Kahonen, Mika; Lehtimaki, Terho; Raitoharju, Emma; Havulinna, Aki; Perola, Markus; Raitakari, Olli; Salomaa, Veikko; Ala-Korpela, Mika; Kettunen, Johannes; McGlynn, Maree; Kelly, Jason; Wlodek, Mary E.; Lewandowski, Paul A.; Delbridge, Lea M.; Burrell, Louise M.; Inouye, Michael; Harrap, Stephen B.; Charchar, Fadi J. (Wiley, 2017)
    Background-Cardiac hypertrophy increases the risk of developing heart failure and cardiovascular death. The neutrophil inflammatory protein, lipocalin-2 (LCN2/NGAL), is elevated in certain forms of cardiac hypertrophy and acute heart failure. However, a specific role for LCN2 in predisposition and etiology of hypertrophy and the relevant genetic determinants are unclear. Here, we defined the role of LCN2 in concentric cardiac hypertrophy in terms of pathophysiology, inflammatory expression networks, and genomic determinants. Methods and Results-We used 3 experimental models: a polygenic model of cardiac hypertrophy and heart failure, a model of intrauterine growth restriction and Lcn2-knockout mouse; cultured cardiomyocytes; and 2 human cohorts: 114 type 2 diabetes mellitus patients and 2064 healthy subjects of the YFS (Young Finns Study). In hypertrophic heart rats, cardiac and circulating Lcn2 was significantly overexpressed before, during, and after development of cardiac hypertrophy and heart failure. Lcn2 expression was increased in hypertrophic hearts in a model of intrauterine growth restriction, whereas Lcn2-knockout mice had smaller hearts. In cultured cardiomyocytes, Lcn2 activated molecular hypertrophic pathways and increased cell size, but reduced proliferation and cell numbers. Increased LCN2 was associated with cardiac hypertrophy and diastolic dysfunction in diabetes mellitus. In the YFS, LCN2 expression was associated with body mass index and cardiac mass and with levels of inflammatory markers. The single-nucleotide polymorphism, rs13297295, located near LCN2 defined a significant cis-eQTL for LCN2 expression. Conclusions-Direct effects of LCN2 on cardiomyocyte size and number and the consistent associations in experimental and human analyses reveal a central role for LCN2 in the ontogeny of cardiac hypertrophy and heart failure.
  • Johnson, Linda S. B.; Salonen, Minna; Kajantie, Eero; Conen, David; Healey, Jeff S.; Osmond, Clive; Eriksson, Johan G. (Wiley, 2017)
    Background-Early life risk factors are associated with cardiometabolic disease, but have not been fully studied in atrial fibrillation (AF). There are discordant results from existing studies of birth weight and AF, and the impact of maternal body size, gestational age, placental size, and birth length is unknown. Methods and Results-The Helsinki Birth Cohort Study includes 13 345 people born as singletons in Helsinki in the years 1934-1944. Follow-up was through national registries, and ended on December 31, 2013, with 907 incident cases. Cox regression analyses stratified on year of birth were constructed for perinatal variables and incident AF, adjusting for offspring sex, gestational age, and socioeconomic status at birth. There was a significant U-shaped association between birth weight and AF (P for quadratic term = 0.01). The lowest risk of AF was found among those with a birth weight of 3.4 kg (3.8 kg for women [85th percentile] and 3.0 kg for men [17th percentile]). High maternal body mass index (>= 30 kg/m(2)) predicted offspring AF; hazard ratio 1.36 (95% CI 1.07-1.74, P = 0.01) compared with normal body mass index ( Conclusions-High maternal body mass index during pregnancy and maternal height are previously undescribed predictors of offspring AF. Efforts to prevent maternal obesity might reduce later AF in offspring. Birth weight has a U-shaped relation to incident AF independent of other perinatal variables.
  • Pokorney, Sean D.; Piccini, Jonathan P.; Stevens, Susanna R.; Patel, Manesh R.; Pieper, Karen S.; Halperin, Jonathan L.; Breithardt, Gunter; Singer, Daniel E.; Hankey, Graeme J.; Hacke, Werner; Becker, Richard C.; Berkowitz, Scott D.; Nessel, Christopher C.; Mahaffey, Kenneth W.; Fox, Keith A. A.; Califf, Robert M.; ROCKET AF Steering Comm; Kaste, Markku (Wiley, 2016)
    Background-Atrial fibrillation is associated with higher mortality. Identification of causes of death and contemporary risk factors for all-cause mortality may guide interventions. Methods and Results-In the Rivaroxaban Once Daily Oral Direct Factor Xa Inhibition Compared with Vitamin K Antagonism for Prevention of Stroke and Embolism Trial in Atrial Fibrillation (ROCKET AF) study, patients with nonvalvular atrial fibrillation were randomized to rivaroxaban or dose-adjusted warfarin. Cox proportional hazards regression with backward elimination identified factors at randomization that were independently associated with all-cause mortality in the 14 171 participants in the intention-to-treat population. The median age was 73 years, and the mean CHADS(2) score was 3.5. Over 1.9 years of median follow-up, 1214 (8.6%) patients died. Kaplan-Meier mortality rates were 4.2% at 1 year and 8.9% at 2 years. The majority of classified deaths (1081) were cardiovascular (72%), whereas only 6% were nonhemorrhagic stroke or systemic embolism. No significant difference in all-cause mortality was observed between the rivaroxaban and warfarin arms (P=0.15). Heart failure (hazard ratio 1.51, 95% CI 1.33-1.70, P= 75 years (hazard ratio 1.69, 95% CI 1.51-1.90, P Conclusions-In a large population of patients anticoagulated for nonvalvular atrial fibrillation, approximate to 7 in 10 deaths were cardiovascular, whereas
  • Viljakainen, Heli T.; Koistinen, Heikki A.; Tervahartiala, Taina; Sorsa, Timo; Andersson, Sture; Makitie, Outi (PUBLIC LIBRARY OF SCIENCE, 2017)
    High leptin concentration, low-grade inflammation, and insulin resistance often coexist in obese subjects; this adverse metabolic milieu may be the main culprit for increased fracture risk and impaired bone quality seen in patients with type 2 diabetes. We examined the associations of leptin, hs (high sensitivity)-CRP and insulin resistance with bone turnover markers (BTMs) and bone characteristics in 55 young obese adults (median BMI 40 kg/m(2)) and 65 non-obese controls. Mean age of the subjects was 19.5 +/- 2.5 years (mean +/- SD). Concentrations of leptin, adiponectin, hs-CRP, MMP-8 and TIMP-1, fasting plasma glucose and insulin (to calculate HOMA), BTMs (BAP, P1NP, CTX-1, and TRAC5b) were measured. Bone characteristics were determined with pQCT at radius and tibia, and with DXA for central sites. Leptin, hs-CRP and HOMA correlated inversely with BTMs: the partial coefficients were 1.5-1.9 fold higher in males than in females. After adjusting for age, BMI, and other endocrine factors, leptin displayed an independent effect in males on radial bone mass (p = 0.019), tibial trabecular density (p = 0.025) and total hip BMD (p = 0.043), with lower densities in males with high leptin. In females, the model adjusting for age, BMI, and other endocrine factors, revealed that hs-CRP had independent effects on radial bone mass (p = 0.034) and lumbar spine BMD (p = 0.016), women with high hs-CRP having lower values. Partial correlations of adiponectin and TIMP-1 with bone characteristics were discrepant; MMP-8 showed no associations. In conclusion, in young obese adults and their controls, leptin, hs-CRP and HOMA associate inversely with BTMs and bone characteristics. Leptin appears to be the key independent effector in males, whereas hs-CRP displayed a predominant role in females.
  • Stenholm, Sari; Solovieva, Svetlana; Viikari-Juntura, Eira; Aalto, Ville; Kivimaki, Mika; Vahtera, Jussi (BioMed Central Ltd, 2017)
    Background: Retirement is a major life transition affecting health behaviors. The aim of this study was to examine within-individual changes in body mass index (BMI) during transition from full-time work to statutory retirement by sex and physical work characteristics. Methods: A multiwave cohort study repeated every 4 years and data linkage to records from retirement registers. Participants were 5426 Finnish public-sector employees who retired on a statutory basis in 2000-2011 and who reported their body weight one to three times prior to (w(-3), w(-2), w(-1)), and one to three times after (w(+1), w(+2), w(+3)) retirement. Results: During the 4-year retirement transition (w(+1), vs. w(-1)) men showed decline in BMI, which was most marked among men with sedentary work (-0.18 kg/m(2), 95% CI -.30 to -0.05). In contrast, BMI increased during retirement transition in women and was most marked among women with diverse (0.14 kg/m(2), 95% CI 0.08 to 0.20) or physically heavy work (0.31 kg/m(2), 95% CI 0.16 to 0.45). Physical activity during leisure time or commuting to work, alcohol consumption or smoking did not explain the observed changes during retirement transition. Conclusions: In this study statutory retirement was associated with small changes in BMI. Weight loss was most visible in men retiring from sedentary jobs and weight gain in women retiring from diverse and physically heavy jobs.