J. Am. Acad. Dermatol . 62 (1): 13–28, quiz 29–30. doi : 10.1016/j.jaad.2009.08.061 .

But during the hormone adjustment period, the body requires more vitamins and proteins instead. [ citation needed ] References [ edit ] ^ Wasmer Andrews, Linda (Mar 28, 2012). "When Spring Brings You Down" .

American Academy of Ophthalmology . 28 April 2018 . Retrieved 18 November 2018 . ^ a b c Michelessi M, Lindsley K (2016).

Fat composition Saturated fats Total saturated 38–43%: Palmitic acid : 25–28% Stearic acid : 12–14% Myristic acid : 1% Unsaturated fats Total unsaturated 56–62% Monounsaturated 47–50%: Oleic acid : 44–47% Palmitoleic acid : 3% Polyunsaturated Linoleic acid : 6–10% [1] Properties Food energy per 100 g (3.5 oz) 3,770 kJ (900 kcal) Melting point backfat: 30–40 °C (86–104 °F) leaf fat: 43–48 °C (109–118 °F) mixed fat: 36–45 °C (97–113 °F) Smoke point 121–218 °C (250–424 °F) Specific gravity at 20 °C (68 °F) 0.917–0.938 Iodine value 45–75 Acid value 3.4 Saponification value 190–205 Unsaponifiable 0.8% Animal fats and oils are lipids derived from animals : oils are liquid at room temperature , and fats are solid.

Clinical Features Thiel et al. (2012) reported a 28-year-old man who presented with persistent myalgias, fever, sore throat, respiratory tract infections, and chronic diarrhea associated with Haemophilus influenza infection.

PMID 11658725 . ^ a b c d Miller, Billie (2017-09-28). "Why do politicians still force women through unwanted pregnancies?

"Pathologic, radiographic and molecular findings in three fetuses diagnosed with HEM/Greenberg skeletal dysplasia". Prenat. Diagn . 28 (4): 309–12. doi : 10.1002/pd.1976 .

Two affected individuals died from status epilepticus at age 6 months and 28 years, respectively. Seizure onset ranged from birth to 24 years, but all had a homogeneous phenotype consisting of complex partial seizures with visual hallucinations and secondary generalization.

Blood gas analysis revealed profound metabolic acidosis (pH of 6.88, base excess of -28 mmol/L, and an elevated anion gap of 33 mmol/L).

In which, an excess of bilirubin being discharged through urine. [1] In case the urine looks in pink, red, or lighter brown is generally caused by beets , blackberries , certain food colorings , hemolytic anemia , renal impairment , urinary tract infection , medication , porphyria , intra- abdominal bleeding , vaginal bleeding , neoplasm located in either bladder or kidneys pathways. [1] If urine looks dark yellow or similar to orange color , the causative factors might be recent uses of vitamin B-containing nutrient supplement, carotene , phenazopyridine , rifampin , warfarin and laxative . [1] The causation or contributing factors of the urine color change to green or blue are those artificial colors seen in foods and drugs, or bilirubin medicines such as methylene blue , and urinary tract infections. [1] Diagnosis [ edit ] Doctor may prescribe some tests to help get the full picture of the situation, such as blood tests , liver function tests , ultrasound for kidneys and bladder, urinalysis , [3] urine culture for infection, and cystoscopy . [1] Doctor may also ask for the medical history to collect information before making a diagnosis. [4] See also [ edit ] Urine § color References [ edit ] ^ a b c d e f g h i j k l m "Urine" . abnormal color: MedlinePlus Medical Encyclopedia . 2019-01-28 . Retrieved 2019-02-10 . ^ "Symptoms and causes" .

The dystrophy was first described in 1967 [1] and initially suspected to denote the same entity as the earlier-described Reis-Bucklers dystrophy , but following a study in 1995 by Kuchle et al. the two look-alike dystrophies were deemed separate disorders. [2] Contents 1 Presentation 2 Genetics 3 Diagnosis 4 See also 5 References 6 External links Presentation [ edit ] To clarify whether Thiel–Behnke corneal dystrophy is a separate entity from Reis-Bucklers corneal dystrophy, Kuchle et al. (1995) examined 28 corneal specimens with a clinically suspected diagnosis of corneal dystrophy of the Bowman layer by light and electron microscopy and reviewed the literature and concluded that 2 distinct autosomal dominant corneal dystrophy of Bowman layer (CBD) exist and proposed the designation CDB type I (geographic or 'true' Reis-Bucklers dystrophy) and CDB type II (honeycomb-shaped or Thiel–Behnke dystrophy).

Prognosis [ edit ] In a Meta-analysis study to conglomerate findings regarding 28 published papers including 158 patients presenting SNUC following up with patients for an average of 14 months showed that at the time of last follow up 25% of patients were alive with no evidence of the disease, 22.4% were alive with presence of the disease, and 52.6% were deceased due to the disease.

"Propofol Infusion Syndrome: A Rare Complication With Potentially Fatal Results" . Critical Care Nurse . 28 (3): 18–25. PMID 18515605 . ^ Sharshar, T. (2008).

Epidemiology Prevalence is unknown but 34 patients with PS (28 females and 6 males) from 15 different families have been reported so far.

In the more recent Barth Syndrome Registry study, 60.2% of affected males had mouth ulcers, 28% had pneumonia, and 10% had blood infections. ... Plasma 3 methylglutaconic acid (3-MGC). In a single study, 28 of 28 affected individuals ranging in age from ten months to 30 years had elevated plasma 3-MGC levels, with an average of 1,088 nmol/L ± 435 (range: 393-2,326 nmol/L) [Vernon et al 2014] (see Table 1). ... These 28 males also showed significantly higher proline levels (291 μmol/L) than controls (165 μmol/L). ... Described in six of 25 patients tested [Spencer et al 2006]. In another study, only two of 28 were found to be hypocholesterolemic, with a mean cholesterol level of 137±26 mg/dL [Vernon et al 2014]. ... LVNC and skeletal myopathy can be seen in Duchenne muscular dystrophy, with a prevalence as high as 28% [Statile et al 2013]. However, in Duchenne muscular dystrophy (in contrast to Barth syndrome) the LVNC tends to worsen over time.

Gripp et al. (2010) found abnormal brain imaging in 27 (96%) of 28 patients with Costello syndrome. All 28 had macrocephaly, and 14 (50%) of 28 had ventriculomegaly, necessitating surgical intervention in 7 (25%). ... Herniation caused Chiari type I malformation in 9 (32%) and syrinx formation in 7 (25%) of 28 patients, and 9 (32%) needed decompression intervention. ... Among these molecules, they sequenced the entire coding region of 4 RAS genes in genomic DNA from 13 individuals with Costello syndrome and 28 individuals with PTPN11-negative Noonan syndrome. ... No mutations in KRAS (190070), NRAS (164790), HRAS, or ERAS (300437) were observed in the 28 individuals with Noonan syndrome or in 1 individual with Costello syndrome. ... Schulz et al. (2008) identified mutations in the HRAS gene in 28 (90.3%) of 31 patients with Costello syndrome.

Lead poisoning can cause a variety of symptoms and signs which vary depending on the individual and the duration of lead exposure. [23] [24] Symptoms are nonspecific and may be subtle, and someone with elevated lead levels may have no symptoms. [25] Symptoms usually develop over weeks to months as lead builds up in the body during a chronic exposure, but acute symptoms from brief, intense exposures also occur. [26] Symptoms from exposure to organic lead, which is probably more toxic than inorganic lead due to its lipid solubility, occur rapidly. [27] Poisoning by organic lead compounds has symptoms predominantly in the central nervous system, such as insomnia , delirium , cognitive deficits , tremor , hallucinations, and convulsions. [22] Symptoms may be different in adults and children; the main symptoms in adults are headache, abdominal pain , memory loss , kidney failure , male reproductive problems, and weakness, pain, or tingling in the extremities. [28] Early symptoms of lead poisoning in adults are commonly nonspecific and include depression, loss of appetite, intermittent abdominal pain, nausea, diarrhea, constipation, and muscle pain . [29] Other early signs in adults include malaise , fatigue, decreased libido , and problems with sleep. [23] An unusual taste in the mouth and personality changes are also early signs. [30] [31] In adults, symptoms can occur at levels above 40 μg/dL, but are more likely to occur only above 50–60 μg/dL. [23] Symptoms begin to appear in children generally at around 60 μg/dL. [5] However, the lead levels at which symptoms appear vary widely depending on unknown characteristics of each individual. [32] At blood lead levels between 25 and 60 μg/dL, neuropsychiatric effects such as delayed reaction times , irritability, and difficulty concentrating, as well as slowed motor nerve conduction and headache can occur. [33] Anemia may appear at blood lead levels higher than 50 μg/dL. [29] In adults, abdominal colic , involving paroxysms of pain, may appear at blood lead levels greater than 80 μg/dL. [24] Signs that occur in adults at blood lead levels exceeding 100 μg/dL include wrist drop and foot drop , and signs of encephalopathy (a condition characterized by brain swelling ), such as those that accompany increased pressure within the skull , delirium , coma, seizures , and headache . [34] In children, signs of encephalopathy such as bizarre behavior, discoordination, and apathy occur at lead levels exceeding 70 μg/dL. [34] For both adults and children, it is rare to be asymptomatic if blood lead levels exceed 100 μg/dL. [24] Acute poisoning [ edit ] In acute poisoning, typical neurological signs are pain, muscle weakness, numbness and tingling , and, rarely, symptoms associated with inflammation of the brain . [28] Abdominal pain, nausea, vomiting, diarrhea, and constipation are other acute symptoms. [35] Lead's effects on the mouth include astringency and a metallic taste. [35] Gastrointestinal problems , such as constipation , diarrhea , poor appetite , or weight loss , are common in acute poisoning. Absorption of large amounts of lead over a short time can cause shock (insufficient fluid in the circulatory system ) due to loss of water from the gastrointestinal tract. [35] Hemolysis (the rupture of red blood cells ) due to acute poisoning can cause anemia and hemoglobin in the urine . [35] Damage to kidneys can cause changes in urination such as decreased urine output . [35] People who survive acute poisoning often go on to display symptoms of chronic poisoning. [35] Chronic poisoning [ edit ] Chronic poisoning usually presents with symptoms affecting multiple systems, [22] but is associated with three main types of symptoms: gastrointestinal , neuromuscular , and neurological . [28] Central nervous system and neuromuscular symptoms usually result from intense exposure, while gastrointestinal symptoms usually result from exposure over longer periods. [35] Signs of chronic exposure include loss of short-term memory or concentration, depression, nausea, abdominal pain, loss of coordination, and numbness and tingling in the extremities. [30] [ unreliable medical source? ] Fatigue, problems with sleep, headaches, stupor, slurred speech, and anemia are also found in chronic lead poisoning. [28] A "lead hue" of the skin with pallor and/or lividity is another feature. [36] [37] A blue line along the gum with bluish black edging to the teeth, known as a Burton line , is another indication of chronic lead poisoning. [38] Children with chronic poisoning may refuse to play or may have hyperkinetic or aggressive behavior disorders. [28] Visual disturbance may present with gradually progressing blurred vision as a result of central scotoma , caused by toxic optic neuritis . [39] Effects on children [ edit ] As lead safety standards become more stringent, fewer children in the US are found to have elevated lead levels. ... ] In addition, lead miners and smelters, plumbers and fitters, auto mechanics, glass manufacturers, construction workers, battery manufacturers and recyclers, firing range workers, and plastic manufacturers are at risk for lead exposure. [86] Other occupations that present lead exposure risks include welding, manufacture of rubber, printing, zinc and copper smelting, processing of ore , combustion of solid waste , and production of paints and pigments. [96] Lead exposure can also occur with intense use of gun ranges , regardless of whether these ranges are indoor or out. [97] Parents who are exposed to lead in the workplace can bring lead dust home on clothes or skin and expose their children. [96] Occupational exposure to lead increases the risk of cardiovascular disease , in particular: stroke , and high blood pressure . [98] Food [ edit ] Lead may be found in food when food is grown in soil that is high in lead, airborne lead contaminates the crops, animals eat lead in their diet, or lead enters the food either from what it was stored or cooked in. [99] In Bangladesh, lead compounds have been added to turmeric to make it more yellow. [100] This is believed to have started in the 1980s and continues as of 2019. [100] It is believed to be one of the main sources of high lead levels in the country. [101] In Hong Kong the maximum allowed lead parts per million is 6 in solid foods and 1 in liquid foods. [102] Paint [ edit ] Some lead compounds are colorful and are used widely in paints, [103] and lead paint is a major route of lead exposure in children. [104] A study conducted in 1998–2000 found that 38 million housing units in the US had lead-based paint, down from a 1990 estimate of 64 million. [105] Deteriorating lead paint can produce dangerous lead levels in household dust and soil. [106] Deteriorating lead paint and lead-containing household dust are the main causes of chronic lead poisoning. [28] The lead breaks down into the dust and since children are more prone to crawling on the floor, it is easily ingested. [105] Many young children display pica , eating things that are not food.

Reporting was often sensational , favoring the direst predictions and shutting out skeptics. [18] Powder (left) and crack cocaine (right) Reporting on the effects of PCE may have been affected by publication bias , a disproportionate publication of studies indicating more severe outcomes as the crack epidemic emerged. [19] Scientific studies that report that PCE has significant effects may be more likely to be published than those that do not. [20] Between 1980 and 1989, 57% of studies showing cocaine has effects on a fetus were accepted by the Society for Pediatric Research, compared with only 11% of studies showing no effects. [21] Findings that other factors such as prematurity were behind symptoms that cocaine-exposed babies showed did not "fit within the narrative of what had become a national scare" and were given less attention. [22] Ideas about severe effects of PCE may have been more readily embraced because they "fit in with cultural stereotypes". [22] At the time, the proposed mechanism by which cocaine harmed fetuses was as a stimulant—it was predicted that cocaine would disrupt normal development of parts of the brain that dealt with stimulation, resulting in problems like bipolar disorder and attention deficit disorder . [2] Reports from the mid-1980s to early 90s raised concerns about links between PCE and slowed growth, deformed limbs, defects of the kidneys and genitourinary and gastrointestinal systems , neurological damage, small head size , atrophy or cysts in the cerebral cortex , bleeding into the brain's ventricles , and obstruction of blood supply in the central nervous system . [19] After the early studies that reported that PCE children would be severely disabled came studies that purported to show that cocaine exposure in utero has no important effects. [17] Almost every prenatal complication originally thought to be due directly to PCE was found to result from confounding factors such as poor maternal nutrition, use of other drugs, depression , and lack of prenatal care . [23] More recently the scientific community has begun to reach an understanding that PCE does have some important effects but that they are not severe as was predicted in the early studies. [17] The effects of PCE are subtle but they exist. [19] [24] [25] Most people who were exposed to cocaine in utero are normal or close to it. [12] Pathophysiology [ edit ] Cocaine is a small enough molecule to pass across the placental barrier into the bloodstream of the fetus. [26] Cocaine, a small molecule, is able to cross the placenta into the bloodstream of the fetus. [26] [27] In fact it may be present in a higher concentration in the amniotic fluid than it is in the mother's bloodstream. [28] The skin of the fetus is able to absorb the chemical directly from the amniotic fluid until the 24th week of pregnancy. [28] Cocaine can also show up in breast milk and affect the nursing baby. [28] [29] The severity of effects depends on how much of the drug is used, how often, and the stage in the development of the fetus. [30] Cocaine prevents the reuptake of the neurotransmitters dopamine , serotonin , and norepinephrine . [20] Thus they stay in the synapse longer, causing excitement of the sympathetic nervous system and evoking a stress response. [21] The euphoria experienced by cocaine users is thought to be largely due to the way it prevents the neurotransmitter serotonin from being reabsorbed by the presynaptic neuron which released it. [31] [1] [20] Use of cocaine during pregnancy can negatively affect both the mother and the fetus, [21] but the ways in which it affects the fetus are poorly understood. [23] There are three main mechanisms by which cocaine exposure harms a fetus: by altering brain chemistry , by altering the expression of certain genes , and by the constriction of blood vessels. [1] The neurotransmitters affected by cocaine are involved in the development of the fetus's brain, [30] so the drug may affect fetal development directly by altering the development of the brain's monoaminergic system. [32] The most important way cocaine affects fetal development is by binding to dopamine receptors . [12] Another possible mechanism by which cocaine harms the fetus may be in part by interfering with blood supply to the uterus. [28] [33] Cocaine causes vasoconstriction (narrowing of blood vessels) in both mother and fetus, which can cause hypoxia in the fetus. [34] Constricting blood vessels causes tissues to receive insufficient blood flow, killing cells, but this effect is less pronounced with cocaine than with nicotine . [8] The reduction in blood flow to the uterus limits the delivery of oxygen and nutrients to the fetus. [16] Cocaine also constricts the blood vessels in the fetus, which is potentially linked to slowed fetal growth and abnormal development of the genitourinary , cardiovascular , digestive , and musculoskeletal systems . [30] Cocaine causes changes in the mother's blood pressure that are thought to be the cause of strokes in the fetus; one study found that 6% of cocaine-exposed infants had had one or more strokes. [28] Such prenatal strokes may be the cause of neurological problems found in some cocaine-exposed infants after birth. [5] Blood vessel contraction can also cause premature labor and premature birth. [16] Cocaine has also been found to enhance the contractility of the tissue in the uterus , another factor that has been suggested as a possible mechanism for its contribution to increased prematurity rates. [33] Increased contractility of the uterus may also be behind the increased likelihood of placental abruption (the placenta tearing away from the uterine wall) which some findings have linked with PCE. [21] Diagnosis [ edit ] Cocaine use during pregnancy can be discovered by asking the mother, but sometimes women will not admit to having used drugs. [35] Mothers may lie for fear of prosecution [35] or having their children taken away, but even when they are willing to tell the truth their memories may not be very accurate. [8] It may also not be possible to be sure of the purity of the drug they have taken. [36] More reliable methods for detecting cocaine exposure involve testing the newborn's hair or meconium (the infant's earliest stool). [37] Hair analysis, however, can give false positives for cocaine exposure, [37] and a newborn may not have enough hair to test. [8] The newborn's urine can be tested for cocaine and metabolites , but it must be collected as soon as possible after birth. [36] It is not known how long after exposure the markers will still show up in a newborn's urine. [35] The mother's urine can also be tested for drugs, but it cannot detect drugs used too far in the past or determine how much or how often the drugs were used. [8] Tests cannot generally detect cocaine use over a week prior to sample collection. [35] Mothers are more honest about cocaine use when their urine is also tested, but many users still deny it. [35] Both maternal and neonatal urine tests can give false negatives . [35] Effects and prognosis [ edit ] Studies have returned widely varying reports of the effects of PCE: some claim the physical disabilities are severe and generalized, others find specific effects, others none all. [1] The timing of the dose of the drug is an important determinant of outcome, in addition to how much is used, for how long, and what kind of care is rendered after birth. [1] Drug use in the first trimester is the most harmful to the fetus in terms of neurological and developmental outcome. [38] The effects of PCE later in a child's life are poorly understood; there is little information about the effects of in utero cocaine exposure on children over the age of five years old. [4] Some studies have found PCE-related differences in height and weight while others have not; these differences are generally either small or are gone by the time children are school age. [4] Much is still not known about what factors may exist to aid children who were exposed to cocaine in utero . [23] It is unknown if the effects of PCE are increased once children reach adolescence, or whether the neural rewiring that occurs during this developmental period attenuates the effects. [20] A review of 27 studies performed between 2006 and 2012 found that cognitive development was mildly to moderately affected in PCE adolescents, but it was not clear how important these effects were in practical terms. [20] Unlike fetal alcohol syndrome , no set of characteristics has been discovered that results uniquely from cocaine exposure in utero . [23] Cocaine exposure in utero may affect the structure and function of the brain, predisposing children to developmental problems later, or these effects may be explained by children of crack-using mothers being at higher risk for domestic violence , deadbeat parenting , and maternal depression . [4] When researchers are able to identify effects of PCE, these effects are typically small. [23] Pregnancy and birth [ edit ] Premature baby Studies have found after controlling for other factors that some effects are present in pregnancies involving cocaine: abruptio placenta , prematurity , low birth weight , and small size compared to babies of the same gestational time. [27] PCE newborns have smaller heads and shorter bodies. [9] [1] PCE effects are more severe when the amounts of cocaine are greater. [27] As many as 17–27% of cocaine-using pregnant women deliver prematurely. [33] In association with prematurity, growth in the womb is reduced, and low birth weight is connected to PCE. [20] There are also data associating spontaneous abortion with cocaine use. [15] Cocaine reduces the appetite and has been linked with reduced maternal weight gain during pregnancy; in addition, constriction of the blood vessels may further limit supply of nutrients to the fetus. [39] Using cocaine while pregnant also heightens the chances of maternal and fetal vitamin deficiencies, respiratory distress syndrome for the baby, and infarction of the bowels. [28] Early reports found that cocaine-exposed babies were at high risk for sudden infant death syndrome ; [19] however, by itself, cocaine exposure during fetal development has not subsequently been identified as a risk factor for the syndrome. [40] Some, but not all, PCE children experience hypertonia (excessive muscle tone ), [41] and reduced reflexes and motor function have been found in babies four to six weeks old. [20] While newborns who were exposed prenatally to drugs such as barbiturates or heroin frequently have symptoms of drug withdrawal ( neonatal abstinence syndrome ), this does not happen with babies exposed to crack in utero ; at least, such symptoms are difficult to separate in the context of other factors such as prematurity or prenatal exposure to other drugs. [16] Mental, emotional, and behavioral outcomes [ edit ] Studies have shown small deficits in behavioral, cognitive, attention, emotional, and language function in PCE infants, children, and adolescents. [20] However, other studies attribute findings of negative effects on cognitive development to confounding factors. [8] Studies suggest that the environment in which a child grows up makes a more important contribution to outcome in cognitive, behavioral and other outcomes than does the cocaine exposure itself. [9] School performance is mildly affected in older children. [27] In IQ studies, cocaine-exposed children do not appear to score lower than others. [1] Although PCE is correlated with low IQ scores, scientists generally believe that PCE alone does not cause this effect; rather it is more likely due to associated factors. [9] In school-age and younger children, PCE does not appear in studies to predispose children to poorer intellectual performance. [4] Poor performance on IQ tests could actually be due to trouble with sustaining attention if the tests fail to account for this factor separately. [8] Cocaine causes impaired growth of the fetus's brain, an effect that is most pronounced with high levels of cocaine and prolonged duration of exposure throughout all three trimesters of pregnancy. [41] Prenatal cocaine exposure has been found to affect the cognitive performance of individuals and affect speech and language development, behavior, physical and cognitive growth, and function. ... PMID 12680368 . ^ Chandler & Lane 2014 , p. 25. ^ a b c d Frank, Deborah A.; Augustyn, Marilyn; Knight, Wanda Grant; Pell, Tripler; Zuckerman, Barry (28 March 2001). "Growth, Development, and Behavior in Early Childhood Following Prenatal Cocaine Exposure" . ... BBC News . 10 August 2010. ^ Gaines & Kremling 2013 , p. 452. ^ Connors 2007 . sfn error: no target: CITEREFConnors2007 ( help ) ^ a b Chandler & Lane 2014 , p. 28. ^ a b Chandler & Lane 2014 , p. 22. ^ a b Zuckerman & Frank 2012 , p. 125.

The Pediatric Infectious Disease Journal . 28 (3 Suppl): S50–3. doi : 10.1097/INF.0b013e3181967bee . ... Viral Gastroenteritis . Arch. Virol. Suppl . 12 . pp. 119–28. doi : 10.1007/978-3-7091-6553-9_14 . ... The Pediatric Infectious Disease Journal . 28 (3 Suppl): S57–9. doi : 10.1097/INF.0b013e3181967c16 . ... The Pediatric Infectious Disease Journal . 28 (3 Suppl): S60–2. doi : 10.1097/INF.0b013e3181967c29 . ... "Recommendations for rotavirus vaccination: A worldwide perspective". Vaccine . 28 (31): 5100–8. doi : 10.1016/j.vaccine.2010.04.108 .

Centers for Disease Control and Prevention (CDC) . 28 October 2015. Archived from the original on 12 March 2016 . ... Centers for Disease Control and Prevention (CDC) . 28 October 2015. Archived from the original on 12 March 2016 . ... "Role of environmental surveillance in determining the risk of hospital-acquired legionellosis: A national surveillance study with clinical correlations" (PDF) . Infect Control Hosp Epidemiol . 28 (7): 818–824. doi : 10.1086/518754 . ... The Washington Post . Archived from the original on 28 March 2016 . Retrieved 31 March 2016 . ^ McFarland M (10 September 2019). ... Retrieved 1 May 2018 . ^ "Third case of Legionnaires reported at Quincy veterans home" . wqad.com . 29 November 2017. Archived from the original on 28 December 2017 . Retrieved 1 May 2018 . ^ "Disneyland tower suggested as Legionnaires' disease source" .