Jump to main content=20
Jump to navigation=20
nature.com homepage
Publications A-Z inde= x
Browse by subject=20

=20

Journal = home > Archive= > Epidemiology > Full = text

Short Communication

British Journal of Cancer (2009) 100, = 185=E2=80=93187.=20 doi:10.1038/sj.bjc.6604813 http://www.bjcancer.com/
Publish= ed online=20 9 December 2008

Seasonality of birth in children with central nervous = system tumours=20 in Denmark, 1970=E2=80=932003

L S Schmidt¹,=20 K Grell¹,=20 K Frederiksen¹,=20 C Johansen¹,=20 K Schmiegelow^2,3,4=20 and J Sch=C3=BCz¹

¹Institute of Cancer Epidemiology, Danish = Cancer=20 Society, Strandboulevarden 49, DK-2100 Copenhagen =C3=98, Denmark
²Department of Paediatrics, Copenhagen = University=20 Hospital, Denmark
³The Medical Faculty, University of = Copenhagen,=20 Copenhagen, Denmark

Correspondence: Dr LS Schmidt, E-mail: samsoe@cancer.dk

⁴K Schmiegelow holds the Danish = Childhood=20 Cancer Foundation Professorship in Paediatric Oncology

Received 9 October 2008; Revised=20 4 November 2008; Accepted 13 November 2008; = Published online=20 9 December 2008.

Top of page

Abstract

Materials=20 and methods=20
Results=20
Discussion=20
References=20
Acknowledgements=20
Figures=20 and Tables

We investigated possible seasonal variation of = births among=20 children <20 years with a central nervous system tumour in Denmark=20 (N=3D1640), comparing them with 2 582 714 children born = between=20 1970 and 2003. No such variation was seen overall, but ependymoma showed = seasonal variation.

Keywords:

brain tumour, central nervous system tumour, = seasonal=20 variation, birth, ependymoma, risk factor

Tumours of the central nervous system (CNS) are the = second most=20 frequent malignancy in childhood and the leading cause of death from = childhood=20 cancer (Little,=20 1999). The aetiology is in most cases unknown, and likely to differ = among=20 the different morphological subgroups. Approximately 5% are associated = with=20 genetic syndromes such as neurofibromatosis and tuberous sclerosis=20 (Little,=20 1999). The only well-established environmental risk factor is = ionising=20 radiation (Wakeford,=20 2004).

A few studies have reported marked and significant = seasonality of=20 birth among patients with a CNS tumour (Yamakawa=20 et al, 1982; Heuch=20 et al, 1998; Feltbower=20 et al, 2001; McNally=20 et al, 2002; Brenner=20 et al, 2004; Halperin=20 et al, 2004; Koch=20 et al, 2006; Mainio=20 et al, 2006; Hoffman=20 et al, 2007). However, there is considerable variability = across=20 studies with respect to which histological subgroup showed the effect.=20 Differences in study design and statistical methods may have contributed = to the=20 observed differences.

Seasonal variation in birth of patients diagnosed with a = specific=20 disease, which differs from the underlying seasonality of births in the = general=20 population, suggests an environmental factor operating at conception, = during=20 pregnancy or in the neonatal period. Such a seasonal pattern may reflect = for=20 example variation in exposure to sunlight or to infections or variation = of the=20 diet.

We used nationwide cancer and population registers to = determine=20 whether there is a seasonal pattern in the births of children who later = develop=20 a CNS tumour compared with the distribution of births of the general = population=20 in Denmark.

Top of page

Materials and methods

Materials=20 and methods=20
Results=20
Discussion=20
References=20
Acknowledgements=20
Figures=20 and Tables

All children 0=E2=80=9319 years of age, who were = diagnosed with a primary=20 CNS tumour in the period 1970=E2=80=932003 and registered in the Danish = Cancer Registry,=20 were included. Secondary tumours were excluded as treatment of a primary = cancer=20 is a known risk factor for secondary cancers (Maule=20 et al, 2007). We included only tumours with a topography and=20 morphology code defined in the International Childhood Cancer = Classification=20 second edition (ICCC-2; Kramarova=20 and Stiller, 1996). In the period 1980=E2=80=931996, all cases were = validated using=20 their medical records (Thorsteinsson=20 et al, 2005).

The reference group included children born in = 1970=E2=80=932003,=20 identified in the national Central Population Register (CPR) established = in 1968=20 and subsequently used for all official personal registration of Danish = citizens=20 and residents. All live-born children are assigned a unique 10-digit CPR = number,=20 including the date of birth and gender code. A test for a sinusoidal = variation=20 was applied to evaluate changes of CNS tumour incidence by month of = birth,=20 adjusted for the background distribution of births (Walter=20 and Elwood, 1975). The deviation of observed from expected numbers = of cases=20 was compared with a <= SUP>2-distribution=20 with 2 degrees of freedom, and the timing of the peak was calculated. = For=20 comparison with a recent study (Hoffman=20 et al, 2007), we defined the same subgroups by gender and = age, young=20 children aged 0=E2=80=934 years at diagnosis and older children = (5=E2=80=9319 years).

Top of page

Results

Materials=20 and methods=20
Results=20
Discussion=20
References=20
Acknowledgements=20
Figures=20 and Tables

We identified 1640 eligible CNS tumour patients = (Table=20 1) and the reference group comprised 2 582 714 children. = Figure=20 1 illustrates the distributions of births in the general population, = among=20 patients with CNS tumours, and among ependymoma patients. Overall, no=20 statistically significant evidence of seasonal variation of births was = observed=20 among patients with CNS tumour (Table=20 1). When stratifying by histology, we found a significant variation = related=20 to month of birth among children with ependymoma, with a peak in early = January=20 and a summer trough (Table=20 1). When examined by age and sex, ependymoma, showed a significant = seasonal=20 variation only at ages 5=E2=80=9319 years, and among girls = (Table=20 1), but numbers in subgroups were small.

Figure=20 1.

Distribution of births per month among patients with Central nervous = system=20 (CNS) tumours, ependymoma and among children in Denmark.

Full=20 figure and legend (69K)

Table=20 1 - Evaluation of seasonality of birth by histology, gender and = age.

Full=20 table

Top of page

Discussion

Materials=20 and methods=20
Results=20
Discussion=20
References=20
Acknowledgements=20
Figures=20 and Tables

The major strength of our study is its base in high = quality=20 population-based administrative registers, ensuring complete case = ascertainment=20 and an appropriate unbiased reference group. The Walter and Edwood test = may=20 perform poorly when numbers are small (St=20 Leger, 1976), as in our analyses by gender and age. If the = aetiologically=20 relevant exposure period is during pregnancy, then differences in = gestational=20 age at birth might dilute a possible seasonality effect. As the = proportion of=20 premature births (gestational age <37 weeks) only is 6% = (The=20 Danish National Board of Health, 2007), this is unlikely to have had = a=20 significant influence on our findings.

Examination of seasonal variation of birth in CNS = tumours have had=20 inconsistent results (Yamakawa=20 et al, 1982; Heuch=20 et al, 1998; Feltbower=20 et al, 2001; McNally=20 et al, 2002; Halperin=20 et al, 2004; Hoffman=20 et al, 2007), and overall, no seasonal pattern of birth is = suggested.=20 Seasonal variations sometimes seen for diagnostic subgroups were not = consistent,=20 so chance may have operated. Such random effects may also explain the=20 significant seasonality for ependymomas in children aged 5=E2=80=9319 = years and at all=20 ages in girls, as no aetiological differences in the ependymomas are = known in=20 these subsets. As associations in the same direction were found for = younger=20 children and for boys, the absence of statistical significance may = reflect a=20 lack of power.

Notably, all previous positive findings regardless of = subgroup=20 have concerned a peak of births in the fall or winter, but most lacked = an=20 appropriate population-based comparison group.

Ependymoma showed seasonality in only one previous study = (McNally=20 et al, 2002), although the peak observed in February was not=20 statistically significant (Edwards test P=3D0.10). Astrocytoma = showed a=20 seasonal pattern in two studies (Heuch=20 et al, 1998; McNally=20 et al, 2002), and medulloblastoma seasonality by month of = birth in=20 three (Yamakawa=20 et al, 1982; Heuch=20 et al, 1998; Hoffman=20 et al, 2007).

Studies of the risk of adult brain tumours have, as with = children,=20 all found a peak of birth in winter (Brenner=20 et al, 2004; Halperin=20 et al, 2004; Koch=20 et al, 2006; Mainio=20 et al, 2006), although no studies from the southern = hemisphere are=20 available.

Dates of diagnosis showed seasonal variation and strong = evidence=20 of space-time clustering in the United Kingdom among children with = astrocytoma=20 and ependymoma, also supporting a role of infections in their aetiology = (McNally=20 et al, 2002); however, in Sweden clustering was not observed = (Hjalmars=20 et al, 1999). When interpreting these results one should keep = in mind=20 that the interval between the onset of disease and diagnosis is variable = and=20 often long because of a combination of unspecific or initially few = symptoms,=20 patients' delay, as well as doctors' delay.

Seasonal variation of birth is a fairly crude proxy = measure for=20 more specific exposures that vary seasonally around the time of = conception,=20 during pregnancy or in the neonatal period. It is unclear whether this = seasonal=20 variation of births in CNS tumour reflects variations in exposure to = specific=20 infections, variable levels of the burden of community infections or = other=20 factors. Some studies have suggested that exposure to infections of the = mother=20 or the child around the time of birth may be associated with increased = risk of=20 certain CNS tumours in children (Linet=20 et al, 1996; Linos=20 et al, 1998; Dickinson=20 et al, 2002; McNally=20 et al, 2002). In addition, three polyomaviruses have shown = oncogenic=20 properties when injected into the brain of newborn laboratory animals = (White=20 et al, 2005). Also seasonal changes in hours of sunlight per = month,=20 especially at Northern latitudes, subsequently leads to fluctuation in = vitamin-D=20 levels. Vitamin-D has antiproliferative and pro-apoptotic properties and = may be=20 involved in carcinogenesis (Holick,=20 2007). However, little is known about any role of D-vitamin in CNS = tumours (Ko=20 et al, 2005). Dietary habits may also be related to season, = but=20 relevant data for Denmark are lacking.

Little is known of ependymoma aetiology, partly because = they only=20 account for approximately 10% of CNS tumours in children, and most = studies lack=20 sufficient numbers. A considerable fraction of spinal ependymoma is = associated=20 with mutations in the neurofibromatosis type 2 gene (NF2; Ebert=20 et al, 1999). An inverse association between maternal = consumption of=20 vitamin supplements during pregnancy and ependymoma risk has been = observed (Bunin=20 et al, 1993), whereas no association with birth weight has = been=20 reported (Harder=20 et al, 2008).

As potential proxy exposures to infectious diseases, = space-time=20 clustering has been noted in ependymoma (McNally=20 et al, 2002), and one study reported an association with a = high=20 number of siblings (Altieri=20 et al, 2006).

In conclusion our results confirm the findings from most = previous=20 studies that no seasonal variation of births is apparent, when combining = all=20 histological subgroups of childhood CNS tumours. We cannot exclude that = our=20 finding of a seasonal pattern of births among patients with ependymoma = is simply=20 due to chance. But the fact that all studies which have reported a = seasonal=20 variation of birth, even though evident for different histological = subgroups of=20 CNS tumours, show an excess of births either during fall or during = winter,=20 justifies further analysis of the seasonality of births in large scale=20 studies.

Top of page

Notes

DISCLOSURE/CONFLICT OF INTEREST

The authors declare no conflict of = interest.

Top of page

References

Materials=20 and methods=20
Results=20
Discussion=20
References=20
Acknowledgements=20
Figures=20 and Tables

Altieri A, Castro F, = Bermejo JL,=20 Hemminki K (2006) Association between number of siblings and nervous = system=20 tumors suggests an infectious etiology. Neurology=20 67: 1979=E2=80=931983 | Article= | PubMed | ISI |
Brenner AV, Linet MS, = Shapiro WR,=20 Selker RG, Fine HA, Black PM, Inskip PD (2004) Season of birth and = risk of=20 brain tumors in adults. Neurology 63: 276=E2=80=93281 | PubMed | ChemPort |
Bunin GR, Kuijten RR, = Buckley JD, Rorke=20 LB, Meadows AT (1993) Relation between maternal diet and subsequent = primitive=20 neuroectodermal brain tumors in young children. N Engl J=20 Med 329: = 536=E2=80=93541 | Article |= PubMed | ChemPort |
Dickinson HO, Nyari TA, = Parker L (2002)=20 Childhood solid tumours in relation to infections in the community in = Cumbria=20 during pregnancy and around the time of birth. Br J=20 Cancer 87: = 746=E2=80=93750 | Article | PubMed | ChemPort |
Ebert C, von HM, = Meyer-Puttlitz B,=20 Wiestler OD, Reifenberger G, Pietsch T, von DA (1999) Molecular = genetic=20 analysis of ependymal tumors. NF2 mutations and chromosome 22q loss = occur=20 preferentially in intramedullary spinal ependymomas. Am J=20 Pathol 155: = 627=E2=80=93632 | PubMed | ISI | = ;ChemPort |
Feltbower RG, Pearce MS, = Dickinson HO,=20 Parker L, McKinney PA (2001) Seasonality of birth for cancer in = Northern=20 England, UK. Paediatr Perinat Epidemiol = 15: 338=E2=80=93345 | Article&n= bsp;| PubMed | ChemPort |
Halperin EC, Miranda ML, = Watson DM,=20 George SL, Stanberry M (2004) Medulloblastoma and birth date: = evaluation of 3=20 US datasets. Arch Environ Health 59: 26=E2=80=9330 | Article |&nbs= p;PubMed |
Harder T, Plagemann A, = Harder A (2008)=20 Birth weight and subsequent risk of childhood primary brain tumors: a=20 meta-analysis. Am J Epidemiol 168: 366=E2=80=93373 | Article | PubMed |
Heuch JM, Heuch I, Akslen = LA, Kvale G=20 (1998) Risk of primary childhood brain tumors related to birth=20 characteristics: a Norwegian prospective study. Int J=20 Cancer 77: = 498=E2=80=93503 | Article | PubMed | ChemPort |
Hjalmars U, Kulldorff M, = Wahlqvist Y,=20 Lannering B (1999) Increased incidence rates but no space-time = clustering of=20 childhood astrocytoma in Sweden, 1973=E2=80=931992: a population-based = study of=20 pediatric brain tumors. Cancer 85: 2077=E2=80=932090 | Article | PubMed | ChemPort |
Hoffman S, Schellinger = KA, Propp JM,=20 McCarthy BJ, Campbell RT, Davis FG (2007) Seasonal variation in = incidence of=20 pediatric medulloblastoma in the United States, 1995=E2=80=932001. = Neuroepidemiology 29:=20 89=E2=80=9395 | Article | PubMed |
Holick MF (2007) Vitamin = D=20 deficiency. N Engl J Med 357: 266=E2=80=93281 | Article | <= A=20 class=3Dreftxt title=3D"Article on PubMed - "=20 = href=3D"http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?holding=3Dnpg&c= md=3DRetrieve&db=3DPubMed&list_uids=3D17634462&dopt=3DAbstrac= t">PubMed | ChemPort |
Ko P, Eyles D, Burne T, = kay-Sim A,=20 McGrath JJ (2005) Season of birth and risk of brain tumors in adults. = Neurology 64:=20 1317 | PubMed | ChemPort |
Koch HJ, = Klinkhammer-Schalke M,=20 Hofstadter F, Bogdahn U, Hau P (2006) Seasonal patterns of birth in = patients=20 with glioblastoma. Chronobiol Int 23: 1047=E2=80=931052 | Article |&n= bsp;PubMed | ChemPort |
Kramarova E, Stiller CA = (1996) The=20 international classification of childhood cancer. Int J=20 Cancer 68: = 759=E2=80=93765 | Article | PubMed | ISI | = ;ChemPort |
Linet MS, Gridley G, = Cnattingius S,=20 Nicholson HS, Martinsson U, Glimelius B, Adami HO, Zack M (1996) = Maternal and=20 perinatal risk factors for childhood brain tumors (Sweden). Cancer Causes Control 7:=20 437=E2=80=93448 | Article | PubMed | ISI | = ;ChemPort |
Linos A, Kardara M, = Kosmidis H,=20 Katriou D, Hatzis C, Kontzoglou M, Koumandakis E, = Tzartzatou-Stathopoulou F=20 (1998) Reported influenza in pregnancy and childhood tumour. Eur J Epidemiol 14:=20 471=E2=80=93475 | Article |&nbs= p;PubMed | ISI | = ;ChemPort |
Little J (1999) Epidemiology of Childhood Cancer. IARC = Scientific=20 Publication: Lyon
Mainio A, Hakko H, = Koivukangas J,=20 Niemela A, Rasanen P (2006) Winter birth in association with a risk of = brain=20 tumor among a Finnish patient population. Neuroepidemiology 27:=20 57=E2=80=9360 | Article | PubMed |
Maule M, Scelo G, Pastore = G, Brennan=20 P, Hemminki K, Tracey E, Sankila R, Weiderpass E, Olsen JH, McBride = ML,=20 Brewster DH, Pompe-Kirn V, Kliewer EV, Chia KS, Tonita JM, Martos C, = Jonasson=20 JG, Merletti F, Boffetta P (2007) Risk of second malignant neoplasms = after=20 childhood leukemia and lymphoma: an international study. J=20 Natl Cancer Inst 99: = 790=E2=80=93800 | Article | PubMed |
McNally RJ, Cairns DP, = Eden OB,=20 Alexander FE, Taylor GM, Kelsey AM, Birch JM (2002) An infectious = aetiology=20 for childhood brain tumours? Evidence from space-time clustering and=20 seasonality analyses. Br J Cancer 86: 1070=E2=80=931077 | Article | PubMed | ISI | = ;ChemPort |
St Leger AS (1976) = Comparison of two=20 tests for seasonality in epidemiological data. Appl=20 Stat 25: = 280=E2=80=93286 | Article |
The Danish National Board = of Health=20 (2007) [Half-yearly report from the Danish Birthregistry] vol 15, http://www.sst.dk/
Thorsteinsson R, Sorensen = M, Jensen=20 TL, Bernhardtsen TM, Gjerris F, Carstensen H, Schmiegelow K, = Raaschou-Nielsen=20 O (2005) [Central nervous system tumours in children. An evaluation of = the=20 completeness and validity of the Cancer Registry]. Ugeskr=20 Laeger 167: = 3782=E2=80=933785 | PubMed |
Wakeford R (2004) The = cancer=20 epidemiology of radiation. Oncogene 23: 6404=E2=80=936428 | Article | PubMed | ISI | = ;ChemPort |
Walter SD, Elwood JM = (1975) A test=20 for seasonality of events with a variable population at risk. Br J Prev Soc Med 29:=20 18=E2=80=9321 | PubMed | ChemPort |
White MK, Gordon J, Reiss = K, Del VL,=20 Croul S, Giordano A, Darbinyan A, Khalili K (2005) Human = polyomaviruses and=20 brain tumors. Brain Res Brain Res Rev = 50: 69=E2=80=9385 | Article&= nbsp;| PubMed | ChemPort |
Yamakawa Y, Fukui M, = Kinoshita K,=20 Kano E (1982) [Seasonal variation of birth incidence of children with=20 cerebellar medulloblastoma. A study in Fukuoka-Ohita area and in all = Japan].=20 Neurol Med Chir (Tokyo) 22: 1002=E2=80=931008 | Article | PubMed | ChemPort |

Top of page

Acknowledgements

Materials=20 and methods=20
Results=20
Discussion=20
References=20
Acknowledgements=20
Figures=20 and Tables

This work was supported by a grant from the Danish = Cancer Society=20 (229070559102).

Top=20 of page=20

Extra navigation

Home
For=20 authors
Services =

ARTICLE NAVIGATION - FULL TEXT

Pre= vious | Nex= t

Expor= t=20 citation
E= xport=20 references

Papers=20 by Schmidt
Papers=20 by Sch=C3=BCz

nature jobs

Tenure-track = Positions=20 in Neuroscience
- Neurocentre Magendie INSERM 862, Bordeaux=20
- Bordeaux 33077 Cedex France
Biostatistician = / Bioinformatician
- King's College London=20
- London United Kingdom

More science = jobs

Post a job = for=20 free

Top

British Journal of Cancer
ISSN: 0007-0920
EISSN: 1532-1827
=C2=A9 2009 Cancer Research = UK=20

partner of AGORA, HINARI, OARE, = INASP,=20 CrossRef and COUNTER

").append(res.responseText.replac= e(//g,"")).find(selector):res.responseText);self.= each(callback,[res.responseText,status,res]);}});return = this;},serialize:function(){return = jQuery.param(this.serializeArray());},serializeArray:function(){return = this.map(function(){return = jQuery.nodeName(this,"form")?jQuery.makeArray(this.elements):this;}).filt= er(function(){return = this.name&&!this.disabled&&(this.checked||/select|textarea/i.test(this.no= deName)||/text|hidden|password/i.test(this.type));}).map(function(i,elem)= {var val=3DjQuery(this).val();return = val=3D=3Dnull?null:val.constructor=3D=3DArray?jQuery.map(val,function(val= ,i){return{name:elem.name,value:val};}):{name:elem.name,value:val};}).get= ();}});jQuery.each("ajaxStart,ajaxStop,ajaxComplete,ajaxError,ajaxSuccess= ,ajaxSend".split(","),function(i,o){jQuery.fn[o]=3Dfunction(f){return = this.bind(o,f);};});var = jsc=3Dnow();jQuery.extend({get:function(url,data,callback,type){if(jQuery= .isFunction(data)){callback=3Ddata;data=3Dnull;}return = jQuery.ajax({type:"GET",url:url,data:data,success:callback,dataType:type}= );},getScript:function(url,callback){return = jQuery.get(url,null,callback,"script");},getJSON:function(url,data,callba= ck){return = jQuery.get(url,data,callback,"json");},post:function(url,data,callback,ty= pe){if(jQuery.isFunction(data)){callback=3Ddata;data=3D{};}return = jQuery.ajax({type:"POST",url:url,data:data,success:callback,dataType:type= });},ajaxSetup:function(settings){jQuery.extend(jQuery.ajaxSettings,setti= ngs);},ajaxSettings:{url:location.href,global:true,type:"GET",timeout:0,c= ontentType:"application/x-www-form-urlencoded",processData:true,async:tru= e,data:null,username:null,password:null,accepts:{xml:"application/xml, = text/xml",html:"text/html",script:"text/javascript, = application/javascript",json:"application/json, = text/javascript",text:"text/plain",_default:"*/*"}},lastModified:{},ajax:= function(s){s=3DjQuery.extend(true,s,jQuery.extend(true,{},jQuery.ajaxSet= tings,s));var = jsonp,jsre=3D/=3D\?(&|$)/g,status,data,type=3Ds.type.toUpperCase();if(s.d= ata&&s.processData&&typeof = s.data!=3D"string")s.data=3DjQuery.param(s.data);if(s.dataType=3D=3D"json= p"){if(type=3D=3D"GET"){if(!s.url.match(jsre))s.url+=3D(s.url.match(/\?/)= ?"&":"?")+(s.jsonp||"callback")+"=3D?";}else = if(!s.data||!s.data.match(jsre))s.data=3D(s.data?s.data+"&":"")+(s.jsonp|= |"callback")+"=3D?";s.dataType=3D"json";}if(s.dataType=3D=3D"json"&&(s.da= ta&&s.data.match(jsre)||s.url.match(jsre))){jsonp=3D"jsonp"+jsc++;if(s.da= ta)s.data=3D(s.data+"").replace(jsre,"=3D"+jsonp+"$1");s.url=3Ds.url.repl= ace(jsre,"=3D"+jsonp+"$1");s.dataType=3D"script";window[jsonp]=3Dfunction= (tmp){data=3Dtmp;success();complete();window[jsonp]=3Dundefined;try{delet= e = window[jsonp];}catch(e){}if(head)head.removeChild(script);};}if(s.dataTyp= e=3D=3D"script"&&s.cache=3D=3Dnull)s.cache=3Dfalse;if(s.cache=3D=3D=3Dfal= se&&type=3D=3D"GET"){var ts=3Dnow();var = ret=3Ds.url.replace(/(\?|&)_=3D.*?(&|$)/,"$1_=3D"+ts+"$2");s.url=3Dret+((= ret=3D=3Ds.url)?(s.url.match(/\?/)?"&":"?")+"_=3D"+ts:"");}if(s.data&&typ= e=3D=3D"GET"){s.url+=3D(s.url.match(/\?/)?"&":"?")+s.data;s.data=3Dnull;}= if(s.global&&!jQuery.active++)jQuery.event.trigger("ajaxStart");var = remote=3D/^(?:\w+:)?\/\/([^\/?#]+)/;if(s.dataType=3D=3D"script"&&type=3D=3D= "GET"&&remote.test(s.url)&&remote.exec(s.url)[1]!=3Dlocation.host){var = head=3Ddocument.getElementsByTagName("head")[0];var = script=3Ddocument.createElement("script");script.src=3Ds.url;if(s.scriptC= harset)script.charset=3Ds.scriptCharset;if(!jsonp){var = done=3Dfalse;script.onload=3Dscript.onreadystatechange=3Dfunction(){if(!d= one&&(!this.readyState||this.readyState=3D=3D"loaded"||this.readyState=3D= =3D"complete")){done=3Dtrue;success();complete();head.removeChild(script)= ;}};}head.appendChild(script);return undefined;}var = requestDone=3Dfalse;var xhr=3Dwindow.ActiveXObject?new = ActiveXObject("Microsoft.XMLHTTP"):new = XMLHttpRequest();if(s.username)xhr.open(type,s.url,s.async,s.username,s.p= assword);else=0A= xhr.open(type,s.url,s.async);try{if(s.data)xhr.setRequestHeader("Content-= Type",s.contentType);if(s.ifModified)xhr.setRequestHeader("If-Modified-Si= nce",jQuery.lastModified[s.url]||"Thu, 01 Jan 1970 00:00:00 = GMT");xhr.setRequestHeader("X-Requested-With","XMLHttpRequest");xhr.setRe= questHeader("Accept",s.dataType&&s.accepts[s.dataType]?s.accepts[s.dataTy= pe]+", = */*":s.accepts._default);}catch(e){}if(s.beforeSend&&s.beforeSend(xhr,s)=3D= =3D=3Dfalse){s.global&&jQuery.active--;xhr.abort();return = false;}if(s.global)jQuery.event.trigger("ajaxSend",[xhr,s]);var = onreadystatechange=3Dfunction(isTimeout){if(!requestDone&&xhr&&(xhr.ready= State=3D=3D4||isTimeout=3D=3D"timeout")){requestDone=3Dtrue;if(ival){clea= rInterval(ival);ival=3Dnull;}status=3DisTimeout=3D=3D"timeout"&&"timeout"= ||!jQuery.httpSuccess(xhr)&&"error"||s.ifModified&&jQuery.httpNotModified= (xhr,s.url)&&"notmodified"||"success";if(status=3D=3D"success"){try{data=3D= jQuery.httpData(xhr,s.dataType,s.dataFilter);}catch(e){status=3D"parserer= ror";}}if(status=3D=3D"success"){var = modRes;try{modRes=3Dxhr.getResponseHeader("Last-Modified");}catch(e){}if(= s.ifModified&&modRes)jQuery.lastModified[s.url]=3DmodRes;if(!jsonp)succes= s();}else=0A= jQuery.handleError(s,xhr,status);complete();if(s.async)xhr=3Dnull;}};if(s= .async){var = ival=3DsetInterval(onreadystatechange,13);if(s.timeout>0)setTimeout(funct= ion(){if(xhr){xhr.abort();if(!requestDone)onreadystatechange("timeout");}= },s.timeout);}try{xhr.send(s.data);}catch(e){jQuery.handleError(s,xhr,nul= l,e);}if(!s.async)onreadystatechange();function = success(){if(s.success)s.success(data,status);if(s.global)jQuery.event.tr= igger("ajaxSuccess",[xhr,s]);}function = complete(){if(s.complete)s.complete(xhr,status);if(s.global)jQuery.event.= trigger("ajaxComplete",[xhr,s]);if(s.global&&!--jQuery.active)jQuery.even= t.trigger("ajaxStop");}return = xhr;},handleError:function(s,xhr,status,e){if(s.error)s.error(xhr,status,= e);if(s.global)jQuery.event.trigger("ajaxError",[xhr,s,e]);},active:0,htt= pSuccess:function(xhr){try{return!xhr.status&&location.protocol=3D=3D"fil= e:"||(xhr.status>=3D200&&xhr.status<300)||xhr.status=3D=3D304||xhr.status= =3D=3D1223||jQuery.browser.safari&&xhr.status=3D=3Dundefined;}catch(e){}r= eturn false;},httpNotModified:function(xhr,url){try{var = xhrRes=3Dxhr.getResponseHeader("Last-Modified");return = xhr.status=3D=3D304||xhrRes=3D=3DjQuery.lastModified[url]||jQuery.browser= .safari&&xhr.status=3D=3Dundefined;}catch(e){}return = false;},httpData:function(xhr,type,filter){var = ct=3Dxhr.getResponseHeader("content-type"),xml=3Dtype=3D=3D"xml"||!type&&= ct&&ct.indexOf("xml")>=3D0,data=3Dxml?xhr.responseXML:xhr.responseText;if= (xml&&data.documentElement.tagName=3D=3D"parsererror")throw"parsererror";= if(filter)data=3Dfilter(data,type);if(type=3D=3D"script")jQuery.globalEva= l(data);if(type=3D=3D"json")data=3Deval("("+data+")");return = data;},param:function(a){var = s=3D[];if(a.constructor=3D=3DArray||a.jquery)jQuery.each(a,function(){s.p= ush(encodeURIComponent(this.name)+"=3D"+encodeURIComponent(this.value));}= );else=0A= for(var j in = a)if(a[j]&&a[j].constructor=3D=3DArray)jQuery.each(a[j],function(){s.push= (encodeURIComponent(j)+"=3D"+encodeURIComponent(this));});else=0A= s.push(encodeURIComponent(j)+"=3D"+encodeURIComponent(jQuery.isFunction(a= [j])?a[j]():a[j]));return = s.join("&").replace(/%20/g,"+");}});jQuery.fn.extend({show:function(speed= ,callback){return = speed?this.animate({height:"show",width:"show",opacity:"show"},speed,call= back):this.filter(":hidden").each(function(){this.style.display=3Dthis.ol= dblock||"";if(jQuery.css(this,"display")=3D=3D"none"){var = elem=3DjQuery("<"+this.tagName+" = />").appendTo("body");this.style.display=3Delem.css("display");if(this.st= yle.display=3D=3D"none")this.style.display=3D"block";elem.remove();}}).en= d();},hide:function(speed,callback){return = speed?this.animate({height:"hide",width:"hide",opacity:"hide"},speed,call= back):this.filter(":visible").each(function(){this.oldblock=3Dthis.oldblo= ck||jQuery.css(this,"display");this.style.display=3D"none";}).end();},_to= ggle:jQuery.fn.toggle,toggle:function(fn,fn2){return = jQuery.isFunction(fn)&&jQuery.isFunction(fn2)?this._toggle.apply(this,arg= uments):fn?this.animate({height:"toggle",width:"toggle",opacity:"toggle"}= ,fn,fn2):this.each(function(){jQuery(this)[jQuery(this).is(":hidden")?"sh= ow":"hide"]();});},slideDown:function(speed,callback){return = this.animate({height:"show"},speed,callback);},slideUp:function(speed,cal= lback){return = this.animate({height:"hide"},speed,callback);},slideToggle:function(speed= ,callback){return = this.animate({height:"toggle"},speed,callback);},fadeIn:function(speed,ca= llback){return = this.animate({opacity:"show"},speed,callback);},fadeOut:function(speed,ca= llback){return = this.animate({opacity:"hide"},speed,callback);},fadeTo:function(speed,to,= callback){return = this.animate({opacity:to},speed,callback);},animate:function(prop,speed,e= asing,callback){var optall=3DjQuery.speed(speed,easing,callback);return = this[optall.queue=3D=3D=3Dfalse?"each":"queue"](function(){if(this.nodeTy= pe!=3D1)return false;var = opt=3DjQuery.extend({},optall),p,hidden=3DjQuery(this).is(":hidden"),self= =3Dthis;for(p in = prop){if(prop[p]=3D=3D"hide"&&hidden||prop[p]=3D=3D"show"&&!hidden)return= = opt.complete.call(this);if(p=3D=3D"height"||p=3D=3D"width"){opt.display=3D= jQuery.css(this,"display");opt.overflow=3Dthis.style.overflow;}}if(opt.ov= erflow!=3Dnull)this.style.overflow=3D"hidden";opt.curAnim=3DjQuery.extend= ({},prop);jQuery.each(prop,function(name,val){var e=3Dnew = jQuery.fx(self,opt,name);if(/toggle|show|hide/.test(val))e[val=3D=3D"togg= le"?hidden?"show":"hide":val](prop);else{var = parts=3Dval.toString().match(/^([+-]=3D)?([\d+-.]+)(.*)$/),start=3De.cur(= true)||0;if(parts){var = end=3DparseFloat(parts[2]),unit=3Dparts[3]||"px";if(unit!=3D"px"){self.st= yle[name]=3D(end||1)+unit;start=3D((end||1)/e.cur(true))*start;self.style= [name]=3Dstart+unit;}if(parts[1])end=3D((parts[1]=3D=3D"-=3D"?-1:1)*end)+= start;e.custom(start,end,unit);}else=0A= e.custom(start,val,"");}});return = true;});},queue:function(type,fn){if(jQuery.isFunction(type)||(type&&type= .constructor=3D=3DArray)){fn=3Dtype;type=3D"fx";}if(!type||(typeof = type=3D=3D"string"&&!fn))return queue(this[0],type);return = this.each(function(){if(fn.constructor=3D=3DArray)queue(this,type,fn);els= e{queue(this,type).push(fn);if(queue(this,type).length=3D=3D1)fn.call(thi= s);}});},stop:function(clearQueue,gotoEnd){var = timers=3DjQuery.timers;if(clearQueue)this.queue([]);this.each(function(){= for(var = i=3Dtimers.length-1;i>=3D0;i--)if(timers[i].elem=3D=3Dthis){if(gotoEnd)ti= mers[i](true);timers.splice(i,1);}});if(!gotoEnd)this.dequeue();return = this;}});var = queue=3Dfunction(elem,type,array){if(elem){type=3Dtype||"fx";var = q=3DjQuery.data(elem,type+"queue");if(!q||array)q=3DjQuery.data(elem,type= +"queue",jQuery.makeArray(array));}return = q;};jQuery.fn.dequeue=3Dfunction(type){type=3Dtype||"fx";return = this.each(function(){var = q=3Dqueue(this,type);q.shift();if(q.length)q[0].call(this);});};jQuery.ex= tend({speed:function(speed,easing,fn){var = opt=3Dspeed&&speed.constructor=3D=3DObject?speed:{complete:fn||!fn&&easin= g||jQuery.isFunction(speed)&&speed,duration:speed,easing:fn&&easing||easi= ng&&easing.constructor!=3DFunction&&easing};opt.duration=3D(opt.duration&= &opt.duration.constructor=3D=3DNumber?opt.duration:jQuery.fx.speeds[opt.d= uration])||jQuery.fx.speeds.def;opt.old=3Dopt.complete;opt.complete=3Dfun= ction(){if(opt.queue!=3D=3Dfalse)jQuery(this).dequeue();if(jQuery.isFunct= ion(opt.old))opt.old.call(this);};return = opt;},easing:{linear:function(p,n,firstNum,diff){return = firstNum+diff*p;},swing:function(p,n,firstNum,diff){return((-Math.cos(p*M= ath.PI)/2)+0.5)*diff+firstNum;}},timers:[],timerId:null,fx:function(elem,= options,prop){this.options=3Doptions;this.elem=3Delem;this.prop=3Dprop;if= (!options.orig)options.orig=3D{};}});jQuery.fx.prototype=3D{update:functi= on(){if(this.options.step)this.options.step.call(this.elem,this.now,this)= ;(jQuery.fx.step[this.prop]||jQuery.fx.step._default)(this);if(this.prop=3D= =3D"height"||this.prop=3D=3D"width")this.elem.style.display=3D"block";},c= ur:function(force){if(this.elem[this.prop]!=3Dnull&&this.elem.style[this.= prop]=3D=3Dnull)return this.elem[this.prop];var = r=3DparseFloat(jQuery.css(this.elem,this.prop,force));return = r&&r>-10000?r:parseFloat(jQuery.curCSS(this.elem,this.prop))||0;},custom:= function(from,to,unit){this.startTime=3Dnow();this.start=3Dfrom;this.end=3D= to;this.unit=3Dunit||this.unit||"px";this.now=3Dthis.start;this.pos=3Dthi= s.state=3D0;this.update();var self=3Dthis;function t(gotoEnd){return = self.step(gotoEnd);}t.elem=3Dthis.elem;jQuery.timers.push(t);if(jQuery.ti= merId=3D=3Dnull){jQuery.timerId=3DsetInterval(function(){var = timers=3DjQuery.timers;for(var = i=3D0;ithis.options.duration+this.startTime){this.now=3D= this.end;this.pos=3Dthis.state=3D1;this.update();this.options.curAnim[thi= s.prop]=3Dtrue;var done=3Dtrue;for(var i in = this.options.curAnim)if(this.options.curAnim[i]!=3D=3Dtrue)done=3Dfalse;i= f(done){if(this.options.display!=3Dnull){this.elem.style.overflow=3Dthis.= options.overflow;this.elem.style.display=3Dthis.options.display;if(jQuery= .css(this.elem,"display")=3D=3D"none")this.elem.style.display=3D"block";}= if(this.options.hide)this.elem.style.display=3D"none";if(this.options.hid= e||this.options.show)for(var p in = this.options.curAnim)jQuery.attr(this.elem.style,p,this.options.orig[p]);= }if(done)this.options.complete.call(this.elem);return false;}else{var = n=3Dt-this.startTime;this.state=3Dn/this.options.duration;this.pos=3DjQue= ry.easing[this.options.easing||(jQuery.easing.swing?"swing":"linear")](th= is.state,n,0,1,this.options.duration);this.now=3Dthis.start+((this.end-th= is.start)*this.pos);this.update();}return = true;}};jQuery.extend(jQuery.fx,{speeds:{slow:600,fast:200,def:400},step:= {scrollLeft:function(fx){fx.elem.scrollLeft=3Dfx.now;},scrollTop:function= (fx){fx.elem.scrollTop=3Dfx.now;},opacity:function(fx){jQuery.attr(fx.ele= m.style,"opacity",fx.now);},_default:function(fx){fx.elem.style[fx.prop]=3D= fx.now+fx.unit;}}});jQuery.fn.offset=3Dfunction(){var = left=3D0,top=3D0,elem=3Dthis[0],results;if(elem)with(jQuery.browser){var = parent=3Delem.parentNode,offsetChild=3Delem,offsetParent=3Delem.offsetPar= ent,doc=3Delem.ownerDocument,safari2=3Dsafari&&parseInt(version)<522&&!/a= dobeair/i.test(userAgent),css=3DjQuery.curCSS,fixed=3Dcss(elem,"position"= )=3D=3D"fixed";if(elem.getBoundingClientRect){var = box=3Delem.getBoundingClientRect();add(box.left+Math.max(doc.documentElem= ent.scrollLeft,doc.body.scrollLeft),box.top+Math.max(doc.documentElement.= scrollTop,doc.body.scrollTop));add(-doc.documentElement.clientLeft,-doc.d= ocumentElement.clientTop);}else{add(elem.offsetLeft,elem.offsetTop);while= (offsetParent){add(offsetParent.offsetLeft,offsetParent.offsetTop);if(moz= illa&&!/^t(able|d|h)$/i.test(offsetParent.tagName)||safari&&!safari2)bord= er(offsetParent);if(!fixed&&css(offsetParent,"position")=3D=3D"fixed")fix= ed=3Dtrue;offsetChild=3D/^body$/i.test(offsetParent.tagName)?offsetChild:= offsetParent;offsetParent=3DoffsetParent.offsetParent;}while(parent&&pare= nt.tagName&&!/^body|html$/i.test(parent.tagName)){if(!/^inline|table.*$/i= .test(css(parent,"display")))add(-parent.scrollLeft,-parent.scrollTop);if= (mozilla&&css(parent,"overflow")!=3D"visible")border(parent);parent=3Dpar= ent.parentNode;}if((safari2&&(fixed||css(offsetChild,"position")=3D=3D"ab= solute"))||(mozilla&&css(offsetChild,"position")!=3D"absolute"))add(-doc.= body.offsetLeft,-doc.body.offsetTop);if(fixed)add(Math.max(doc.documentEl= ement.scrollLeft,doc.body.scrollLeft),Math.max(doc.documentElement.scroll= Top,doc.body.scrollTop));}results=3D{top:top,left:left};}function = border(elem){add(jQuery.curCSS(elem,"borderLeftWidth",true),jQuery.curCSS= (elem,"borderTopWidth",true));}function = add(l,t){left+=3DparseInt(l,10)||0;top+=3DparseInt(t,10)||0;}return = results;};jQuery.fn.extend({position:function(){var = left=3D0,top=3D0,results;if(this[0]){var = offsetParent=3Dthis.offsetParent(),offset=3Dthis.offset(),parentOffset=3D= /^body|html$/i.test(offsetParent[0].tagName)?{top:0,left:0}:offsetParent.= offset();offset.top-=3Dnum(this,'marginTop');offset.left-=3Dnum(this,'mar= ginLeft');parentOffset.top+=3Dnum(offsetParent,'borderTopWidth');parentOf= fset.left+=3Dnum(offsetParent,'borderLeftWidth');results=3D{top:offset.to= p-parentOffset.top,left:offset.left-parentOffset.left};}return = results;},offsetParent:function(){var = offsetParent=3Dthis[0].offsetParent;while(offsetParent&&(!/^body|html$/i.= test(offsetParent.tagName)&&jQuery.css(offsetParent,'position')=3D=3D'sta= tic'))offsetParent=3DoffsetParent.offsetParent;return = jQuery(offsetParent);}});jQuery.each(['Left','Top'],function(i,name){var = method=3D'scroll'+name;jQuery.fn[method]=3Dfunction(val){if(!this[0])retu= rn;return = val!=3Dundefined?this.each(function(){this=3D=3Dwindow||this=3D=3Ddocumen= t?window.scrollTo(!i?val:jQuery(window).scrollLeft(),i?val:jQuery(window)= .scrollTop()):this[method]=3Dval;}):this[0]=3D=3Dwindow||this[0]=3D=3Ddoc= ument?self[i?'pageYOffset':'pageXOffset']||jQuery.boxModel&&document.docu= mentElement[method]||document.body[method]:this[0][method];};});jQuery.ea= ch(["Height","Width"],function(i,name){var = tl=3Di?"Left":"Top",br=3Di?"Right":"Bottom";jQuery.fn["inner"+name]=3Dfun= ction(){return = this[name.toLowerCase()]()+num(this,"padding"+tl)+num(this,"padding"+br);= };jQuery.fn["outer"+name]=3Dfunction(margin){return = this["inner"+name]()+num(this,"border"+tl+"Width")+num(this,"border"+br+"= Width")+(margin?num(this,"margin"+tl)+num(this,"margin"+br):0);};});})(); ------=_NextPart_000_0000_01C99A9A.4B75EB30 Content-Type: application/octet-stream Content-Transfer-Encoding: quoted-printable Content-Location: http://www.nature.com/common/scripts/global.js (function($) { $(document).ready(function () { // enables dropdown ads to display whilst maintaining .user-services = visibility aat small resolutions // yes, it involves browser detection, and yes, that is truly = horrible. if (jQuery.browser.mozilla) { =09 var dropdownAd =3D false; =09 // for each descendant of .leaderboard that isn't a

Short Communication

Seasonality of birth in children with central nervous = system tumours=20 in Denmark, 1970=E2=80=932003

Abstract

Keywords:

Materials and methods

Results

Figure=20 1.

Table=20 1 - Evaluation of seasonality of birth by histology, gender and = age.

Discussion

Notes

References

Acknowledgements

MORE ARTICLES LIKE THIS

RESEARCH

Extra navigation

ARTICLE NAVIGATION - FULL TEXT

nature jobs

Tenure-track = Positions=20 in Neuroscience

Biostatistician = / Bioinformatician

nature products