The early Aurignacian dispersal of modern humans into westernmost Eurasia.

Documenting the first appearance of modern humans in a given region is key to understanding the dispersal process and the replacement or assimilation of indigenous human populations such as the Neanderthals. The Iberian Peninsula was the last refuge of Neanderthal populations as modern humans advanced across Eurasia. Here we present evidence of an early Aurignacian occupation at Lapa do Picareiro in central Portugal. Diagnostic artifacts were found in a sealed stratigraphic layer dated 41.1 to 38.1 ka cal BP, documenting a modern human presence on the western margin of Iberia ∼5,000 years earlier than previously known. The data indicate a rapid modern human dispersal across southern Europe, reaching the westernmost edge where Neanderthals were thought to persist. The results support the notion of a mosaic process of modern human dispersal and replacement of indigenous Neanderthal populations.

Effect of gender (gilt and surgically and immunocastrated male) and ractopamine hydrochloride supplementation on growth performance, carcass, and pork quality characteristics of finishing pigs under commercial conditions.

This study evaluated the effects of gender and feeding of ractopamine on growth performance, carcass, and meat quality characteristics of pigs reared under commercial conditions. The study was performed as a randomized complete block design (blocking factor date of start on test) with a 3 × 2 factorial arrangement of treatments: 1) gender [gilt vs. surgical castrate vs. intact males immunocastrated] and 2) ractopamine level (0 vs. 5 g/ton). The study was conducted out over a fixed duration (126 d) from 1 wk after weaning (28 d of age; 8.04 ± 1.31 kg BW) to 154 d of age (111.44 ± 4.67 kg BW) in 3 growth periods: nursery (d 0 to 35 of the study), growing (d 35 to 70), and finishing (d 70 to 126). Ractopamine was fed for the final 28 d of the study (d 98 to 126). Pigs were kept in groups of 10 or 11 in the nursery phase and then moved to the growing-finishing facility where they were kept in groups of 22 to the end of the study. At the end of the growth study, pigs were harvested and carcass and pork quality were evaluated, including consumer evaluation of eating quality. During the nursery, there was no effect of gender (P > 0.05) on G:F, but surgical castrates grew faster (P < 0.05) than intact males and gilts and had greater (P < 0.05) ADFI than intact males. There was no effect of gender (P > 0.05) on ADG in the growing period; however, immunocastrated males had lower ADFI than surgical castrates and greater G:F than surgical castrates and gilts. In finishing, immunocastrated males and surgical castrates had similar ADG but grew faster than gilts; G:F was greater for immunocastrated males than the other genders. Feeding 5 compared to 0 g/ton ractopamine increased ADG and G:F but had no effect (P > 0.05) on carcass yield or fresh meat quality. Carcass yield was lower but percentage lean cut yield was greater for immunocastrated males than for surgical castrates. Longissimus muscle drip loss was greater (P = 0.05) for immunocastrated males than surgical castrates. Gender had no effect (P > 0.05) on consumer panel evaluation. Feeding ractopamine had no effect on pork flavor and tenderness but improved juiciness scores. Odor scores were similar (P > 0.05) for surgical castrates and immunocastrated males that were fed ractopamine. Consumers gave lower liking scores for odor for immunocastrated males than surgical castrates that were not fed ractopamine. This study highlights the feed efficiency and lean cut yield advantage for immunocastrated males compared to surgical castrates and suggests a similar growth response to feeding ractopamine in these genders. Although immunocastrated males had a lower carcass yield and higher drip loss, panelists were not able to detect differences in pork juiciness, flavor, and tenderness when compared to surgical castrate pigs.

Seasonal variation in vitamin D levels in the Canterbury, New Zealand population in relation to available UV radiation.

AIM: The optimal plasma 25-hydroxyvitamin D (25(OH)D) concentration is probably >75 nmol/L but in temperate regions lower levels are common. Few studies report the intensity of solar ultraviolet (UV) radiation when 25(OH)D is measured. We measured plasma 25(OH)D and incident solar UVB radiation in Christchurch and modelled the relationship between them. METHODS: 25(OH)D, total calcium (CaT), ionised calcium (CaI) and parathyroid hormone (PTH) were measured in healthy volunteers (119 female, 82 male; median age 45 years, range 18 to 83) between February and July 2004. Vitamin D-weighted UV energy measurements (dUV) for Christchurch were from the National Institute of Water and Atmospheric Research (NIWA) UV Atlas. RESULTS: In February 2004, 88% of 25(OH)D levels were below 75 nmol/L, increasing to 100% in June and July. Severe deficiency (<12.5 nmol/L) was found in 1.5% of subjects. From February to July, 25(OH)D and CaI fell and CaT rose (p<0.001,<0.01, and <0.001). There was a hyperbolic relationship between PTH and 25OHD while CaT and CaI correlated negatively with PTH (r=-0.30 and -0.33; both p<0.001). Monthly mean dUV intensity ranged from 10 kJ m-2 day-1 in Dec 2003 to 0.5 kJ m-2 day-1 in June 2004. Compartmental modelling estimated that a Christchurch person made 1200 IU/day of vitamin D in mid-summer but only 60 IU/day in midwinter. Daily supplements of 1450 or 2600 IU vitamin D3 are predicted to raise the annual minimum mean plasma 25(OH)D to 75 or 100 nmol/L respectively. CONCLUSIONS: Most Christchurch people are vitamin D deficient most of the time and a daily supplement of 2600 IU vitamin D3 would correct this.

Touch detection of neonatal hypothermia in Nepal.

The use of touch by health workers to detect hypothermia was examined in 250 newborns in Nepal. Palpation of the feet shows fair interobserver agreement (kappa = 0.4-0.7) and high sensitivity (>80%) but low specificity (36%-74%) compared with axillary thermometry. Traditional birth attendants should feel an infant's feet to detect hypothermia.

Effect of a novel phytase on growth performance, bone ash, and mineral digestibility in nursery and grower-finisher pigs.

To compare the effectiveness of 2 phytase enzymes (Phyzyme and Natuphos), growth performance, fibula ash, and Ca and P digestibilities were evaluated in 4 studies. The first 3 studies used 832 pigs (i.e., 288 in the nursery phase, initial BW 8.1 kg; 288 in the grower phase, initial BW 24.2 kg; and 256 in the finisher phase, initial BW 57.8 kg) and were carried out over periods of 28, 42, and 60 d, respectively. Dietary treatments in each study consisted of a positive control [available P (aP) at requirement level]; negative control (Ca remained as in the positive control, and aP at 66, 56, and 40% of the requirement for the nursery, grower, and finisher studies, respectively); negative control plus graded levels of Phyzyme [250, 500, 750, or 1,000; measured as phytase units (FTU)/kg] or Natuphos (250 and 500 FTU/kg for the nursery and grower studies, or 500 and 1,000 FTU/kg for the finisher study) plus a very high dose of Phyzyme (tolerance level, at 10,000 FTU/kg) in the nursery and grower experiments. Across the 3 studies, there was no effect of any dietary treatment on ADFI, but the negative control reduced ADG (10%), G:F (7%), and bone ash (8%) compared with the positive control. In the nursery study, phytase addition increased G:F and bone ash linearly (P < 0.01). In the grower study, phytase increased ADG, G:F, and bone ash linearly (P < 0.01). In the finisher study, phytase addition increased ADG and bone ash linearly (P < 0.01) and increased G:F quadratically (P < 0.05); G:F was, on average, 5% greater (P < 0.05) with Phyzyme than with Natuphos. The fourth study was conducted to investigate the P-releasing efficacy of the 2 phytases. The apparent fecal digestibility of P, measured with chromic oxide as an external marker in 35 pigs (55.9 kg of BW), showed that aP increased (P < 0.001) by 0.17 and 0.06 g (+/- 0.023) per 100 FTU consumed for Phyzyme and Natuphos, respectively. Also, Phyzyme at 10,000 FTU/kg was not detrimental to animal health or growth performance. At doses intended for commercial conditions, Phyzyme proved to be effective in releasing phytate bound P from diets, with an efficacy superior to a commercially available enzyme.

Evaluation of the inclusion of soybean oil and soybean processing by-products to soybean meal on nutrient composition and digestibility in swine and poultry.

This experiment was designed to evaluate the effects of selected soybean (SB) processing byproducts (gums, oil, soapstock, weeds/trash) when added back to soybean meal (SBM) during processing on the resulting nutrient composition, protein quality, nutrient digestibility by swine, and true metabolizable energy (TMEn) content and standardized AA digestibility by poultry. To measure ileal DM and nutrient digestibility, pigs were surgically fitted with a T-cannula in the distal ileum. The concentration of TMEn and the standardized AA digestibility by poultry were determined using the precision fed cecectomized rooster assay. Treatments in the swine experiment included SBM with no by-products; SBM with 1% gum; SBM with 3% gum; SBM with 0.5% soapstock; SBM with 1.5% soapstock; SBM with 2% weeds/trash; SBM with a combination of 3% gum, 1.5% soapstock, and 2% weeds/trash; SBM with 5.4% soybean oil; and roasted SB. A 10 x 10 Latin square design was utilized. The experiment was conducted at the University of Illinois, Urbana-Champaign, and at The Ohio State University, Columbus. In the swine experiment, apparent ileal DM, OM, CP, and AA digestibilities were reduced (P < 0.05) when pigs consumed the combination by-product diet compared with the diet containing no by-products. Apparent ileal digestibilities of DM, CP, and total essential, total nonessential, and total AA were lower (P < 0.05) for any diet containing by-products compared with the diet with no by-products. Apparent ileal digestibilities of DM, OM, CP, and AA were lower (P < 0.05) for the roasted SB-compared with the SB oil-containing diet. In the rooster experiment, TMEn values were greater (P < 0.05) for roasted SB compared with SBM with no by-products and increased linearly as the addition of soapstock increased. Individual, total essential, total nonessential, and total AA digestibilities were lower (P < 0.05) for roosters fed roasted SB versus SBM devoid of by-products. Gums, soapstock, and weeds/trash reduce the nutritive value of the resultant meal when they are added back during processing.

Effects of dietary supplementation with L-carnitine and fat on blood acid-base responses to handling in slaughter weight pigs.

Blood acid-base responses to handling were evaluated in slaughter weight pigs fed diets supplemented with l-carnitine and fat. The study was carried out as a randomized block design with a 2 x 2 factorial arrangement of treatments: 1) dietary L-carnitine supplementation (0 vs. 150 ppm, as-fed basis); and 2) dietary fat supplementation (0 vs. 5%, as-fed basis). Sixty pigs (91.1 +/- 5.14 kg BW) were housed in mixed-gender groups of five and had ad libitum access to test diets (0.68% true ileal digestible lysine, 3,340 kcal of ME/kg, as-fed basis) for 3 wk. At the end of the feeding period (110.3 +/- 7.52 kg BW), pigs were subjected to a standard handling procedure, which consisted of moving individual animals through a facility (12.2 m long x 0.91 m wide) for eight laps (up and down the facility), using electric prods (two times per lap). There was no interaction between dietary L-carnitine and fat supplementation for any measurement. Pigs fed 150 ppm of supplemental L-carnitine had lower baseline blood glucose (P < 0.05) and higher baseline blood lactate (P < 0.05) concentrations than the nonsupplemented pigs. After handling, pigs fed L-carnitine-supplemented diets had a higher (P < 0.05) blood pH and showed a smaller (P < 0.05) decrease in blood pH and base excess than those fed the nonsupplemental diets. Baseline plasma FFA concentrations were higher (P < 0.01) in pigs fed the 5% fat diet. After the handling procedure, blood glucose, lactate, and plasma FFA were higher (P < 0.05) in pigs fed the 5 vs. 0% fat diets, but blood pH, bicarbonate, and base excess were not affected by dietary fat. The handling procedure decreased (P < 0.01) blood pH, bicarbonate, base excess, and total carbon dioxide and increased (P < 0.01) blood lactate, partial pressure of oxygen, and glucose, and also increased (P < 0.01) rectal temperature. Free fatty acid concentrations were increased by handling in pigs fed both 0 and 5% fat and 150 ppm L-carnitine. In conclusion, dietary L-carnitine supplementation at the level and for the feeding period evaluated in the current study had a relatively small but positive effect on decreasing blood pH changes in finishing pigs submitted to handling stress; however, dietary fat supplementation had little effect on blood acid-base balance.

First-line endocrine treatment of breast cancer: aromatase inhibitor or antioestrogen?

Until recently, endocrine therapy for breast cancer was relatively simple. If the tumour expressed hormone receptors, regardless of stage and age, tamoxifen was indicated. While this largely remains the case for premenopausal women, clinical trials in postmenopausal women have broadened our choice to include one of three selective aromatase inhibitors (AIs), the nonsteroidal agents anastrozole or letrozole and the steroidal agent exemestane. Comparative data concerning the efficacy, toxicity, tolerability and cost of AI vs tamoxifen continues to evolve with over 40 000 women slated to be involved in clinical trials. Currently, tamoxifen remains an appropriate choice for adjuvant treatment, and will remain so unless a clear survival advantage emerges for adjuvant AI therapy. However, anastrozole is widely seen as a useful alternative, with particular merit for patients prone to the development of serious tamoxifen side effects. For endocrine therapy naïve advanced disease, several trials have provided evidence that a nonsteroidal AI has replaced tamoxifen as optimal treatment. In the neoadjuvant setting, letrozole was also more effective than tamoxifen, both in terms of response rates and the incidence of breast-conserving surgery, and so AI therefore also dominates this evolving indication. The ongoing adjuvant clinical trials ask all the relevant questions regarding tamoxifen and AI in combination, sequence and duration, except for 5 years of an AI vs a longer period. For both the advanced and early-stage disease, resistance remains the key obstacle to overcome, and trials that combine endocrine agents with signal transduction inhibitors such as HER1 and HER2 kinase inhibitors, farnesyl transferase inhibitors, mTOR inhibitors as well as COX2 inhibitors are being developed in a concerted attempt to address this problem.

Effect of vitamin E, low dose irradiation, and display time on the quality of pork.

A 4×2×3 factorial experiment was designed to investigate the effect of supplemental vitamin E (0, 100, 200, and 300 mg/kg feed), irradiation and days in display on quality characteristics of aerobically packaged ground pork and vacuum packaged loin chops. Color, thiobarbituric acid reactive substances (TBARS), olfactory and sensory characteristics were evaluated. Samples held in display for 3 d were used for sensory evaluation. In the ground pork, irradiation (1.9 kGy) increased "wetdog" flavor, increased a(*) (redness) and decreased L(*) (lightness) and b(*) (yellowness) values but had no effect on TBARS. However, as display time (0, 4, and 8 days) increased; the differences in a(*) values diminished and putrefying and fishy odors were higher in non-irradiated samples than irradiated. Supplemented vitamin E had no effect on TBARS, odor, and color measures; but increased the juiciness of ground pork regardless of irradiation. Similarly, in the loin chops, irradiation (1.5 kGy) increased a(*) value and "wetdog" flavor; but decreased b(*) value regardless of vitamin E supplementation. Also, irradiation reduced putrefying, and fishy odors during longer display times. TBARS increased with increased display time but was not affected by vitamin E supplementation. These results indicate that in aerobically packaged ground pork and vacuum packaged loin chops, radiolytic odors and color changes cannot be mediated with vitamin E supplementation. Display time and irradiation are significant in determining color and odor changes.

Effect of level, source, and time of feeding prior to slaughter of supplementary dietary magnesium on pork quality.

A total of 192 pigs were utilized in a 2×3×3 factorial arrangement with an additional control treatment. The treatments were: (1) magnesium level (1.6 vs. 3.2 g of magnesium pig(-1) day(-1)); (2) magnesium source (sulfate vs. proprionate vs. proteinate); (3) feeding duration (5 vs. 2 vs. 1 day), and a control (no supplementary magnesium). Minolta L(∗) values were lower (P⩽0.05), indicating darker muscle color, for pigs supplemented with 1.6 g magnesium pig(-1) day(-1) compared to the controls while pigs on the 3.2 g magnesium level were intermediate between these two treatments. Animals on the 1 day treatment had a higher (P⩽0.05) ultimate pH and lower (P⩽0.05) Minolta L(∗) compared to those on the 2 days and control treatments, while 5 days pigs were intermediate and had lower L(∗) values compared to the controls. The sulfate and proteinate treatments produced pork with the lower (P⩽0.05) Minolta L(∗) values compared to the controls. Pigs fed the sulfate diet had a lower (P⩽0.05) drip loss compared to those on the control treatment. Results from this study suggest that the lowest level (1.6 g magnesium pig(-1) day(-1)) and the shortest time of supplementation (1 day) may be effective in improving pork color and water-holding capacity.

The impact of longissimus glycolytic potential and short-term feeding of magnesium sulfate heptahydrate prior to slaughter on carcass characteristics and pork quality.

The objective of this study was to compare the effects of longissimus glycolytic potential (GP) and of time of feeding of supplemental magnesium sulfate heptahydrate on carcass and pork quality traits. The study was carried out in a 2 x 2 x 4 factorial arrangement; the treatments were sex (castrate vs gilt), GP (Low [normal] vs High), and time of feeding of magnesium sulfate-fortified diets (0 [control] vs 2 vs 3 vs 5 d prior to slaughter). Glycolytic potential was determined on a biopsy sample of longissimus from the live animal prior to the start of the study. A total of 144 pigs were allotted to the feeding-time treatments on the basis of sex (castrate and gilt), weight, and GP. Pigs were placed in individual pens and had free access to water. Prior to the start of the study, pigs were given ad libitum access to a standard finisher diet. During the study, animals were fed at a fixed level of 2.75 kg of a standard finisher diet/day; the fortified diet contained 3.2 g/d of additional magnesium. At the end of the feeding period, animals were transported to a commercial packing facility and slaughtered within 15 min of arrival. Fresh meat quality was measured on the longissimus. There were no treatment interactions. Carcass traits were similar across time of feeding treatments. Backfat thickness at the last lumbar vertebra and 10th rib were lower (P < 0 .05) for High than for Low GP pigs. High GP pigs had lower ultimate pH (P < 0.001) and higher drip (P < 0.05) and purge loss (P < 0.01) than Low GP pigs. Drip loss was reduced (P < 0.05) for pigs fed the magnesium-fortified diet for 5 and 2 but not for 3 d compared to controls (8.98, 7.29, 7.89, and 7.41 for the 0-, 2-, 3-, and 5-d treatments, respectively, SEM 0.447). Purge loss was similar for all of the time of feeding treatments. Longissimus L* values were lower (P < 0.05) for the 2-d treatment than for the controls. Results from this study suggest an inconsistent effect of short-term feeding of magnesium sulfate on muscle color and drip loss in pigs with both Low (normal) and High GP.

Lightening the lead load in children.

More than 4 percent of preschool-aged children in the United States have blood lead levels above 10 microg per dL (0.50 pmol per L), and these levels have been associated with a decline in IQ. The Centers for Disease Control and Prevention advocates the use of a screening questionnaire to identify lead exposure or toxicity in all children. Primary prevention through the removal of lead from gasoline and paint has led to a reduction of blood lead levels in children. Secondary prevention through paint hazard remediation is effective in homes that have a high lead burden. Children with lead levels of 45 to 69 microg per dL (2.15 to 3.35 pmol per L) should receive chelation therapy using succimer (DMSA) or edetate calcium disodium (CaNa2EDTA). Use of both CaNa2EDTA and dimercaprol (BAL in oil) is indicated in children with blood lead levels higher than 70 microg per dL (3.40 micromol per L). Current treatment recommendations are based on the reduction of blood lead levels, which may not represent a significant overall reduction of the lead burden. Clinical trials of existing agents are needed to determine patient-oriented outcomes, such as the effect on IQ.

Effect of room temperature and dietary amino acid concentration on performance of lactating sows. NCR-89 Committee on Swine Management.

Mixed-parity sows (n = 267) from five research stations were used to investigate whether a reduction of excess dietary amino acids would improve feed intake and performance of lactating sows experiencing heat stress. Experimental treatments included effects of room temperature (warm or hot) and diet (adequate protein [AP] or low protein [LP]). The corn-soybean meal AP diet was formulated to contain 16.5% CP, .8% lysine, and .67% digestible lysine. The LP diet was formulated to contain 13.7% CP, .76% lysine, and .66% digestible lysine using corn, soybean meal, and synthetic lysine. Feed intake during gestation was standardized at 1.8 kg x sow(-1) x d(-1). At parturition, litter size was adjusted to no fewer than nine pigs. Mean high temperature in the warm and hot rooms was 20.4 and 29.2 degrees C and mean low temperature was 17.7 and 27.1 degrees C, respectively. The hot environment reduced (P < .01) feed intake of sows (4.19 vs 6.38 kg/d) during lactation, weaning weight of sows (176.2 vs 193.6 kg), percentage of sows displaying estrus (79.2 vs 93.4%) by d 15 postweaning, and litter growth rate (1.74 vs 2.11 kg/d) and increased (P < .01) respiration rate of sows on d 10 postpartum (71.9 vs 36.5 breaths/min) compared with the warm environment. Litter size and backfat loss of sows were not affected by treatments. No significant diet x room temperature interactions were observed for voluntary feed intake, body weight loss, backfat loss, or respiration rate of sows. Litter growth rate was depressed by feeding the LP diet in the warm room but was improved by feeding the LP diet in the hot room (warm-AP, 2.17; warm-LP, 2.05; hot-AP, 1.71; hot-LP, 1.77 kg/d; P < .05). Reduction of dietary crude protein combined with supplementation of crystalline lysine to reduce concentrations of excess dietary amino acids did not significantly reduce heat stress of sows, but it did support slight improvements in weight gain of litters nursing heat-stressed sows.

Addressing spiritual concerns of patients: family physicians' attitudes and practices.

BACKGROUND: Our goals were to assess family physicians' spiritual well-being, identify their perceived barriers to discussing spiritual issues with patients, and determine how often they have these discussions. METHODS: We mailed a questionnaire to 231 Missouri family physicians (80 residents, 43 faculty, and 108 community physicians). The questionnaire included the Ellison Spiritual Well-being Scale (ESWS), as well as questions about physicians' attitudes toward spirituality and the barriers to and frequency of discussions of spiritual issues with patients. RESULTS: The response rate was 74%. The mean ESWS score indicated that the physician respondents had a high level of spiritual well-being. Nearly all respondents (96%) considered spiritual well-being an important health component, 86% supported referral of hospitalized patients with spiritual questions to chaplains, and 58% believed physicians should address patients' spiritual concerns. Fear of dying was the spiritual issue most commonly discussed, and less than 20% of physicians reported discussing other spiritual topics in more than 10% of patient encounters. Barriers to addressing spiritual issues included lack of time (71%), inadequate training for taking spiritual histories (59%), and difficulty identifying patients who want to discuss spiritual issues (56%). CONCLUSIONS: Family physicians in this survey had high spiritual well-being scores. Most believed spiritual well-being is an important factor in health. Despite this belief, however, most reported infrequent discussions of spiritual issues with patients and infrequent referrals of hospitalized patients to chaplains. Lack of time and training were key barriers to spiritual assessment.

From toxicological problem to therapeutic use: the discovery of the mode of action of 2-(2-nitro-4-trifluoromethylbenzoyl)-1,3-cyclohexanedione (NTBC), its toxicology and development as a drug.

NTBC is a triketone with herbicidal activity that has been shown to have a novel mode of action by inhibiting the enzyme 4-hydroxyphenylpyruvate dioxygenase in plants. Early studies on the toxicity of this compound found that rats treated with NTBC developed corneal lesions. Investigations aimed at understanding the mechanistic basis for the ocular toxicity discovered that the rats developed tyrosinaemia and excreted large amounts of 4-hydroxyphenylpyruvate and 4-hydroxyphenyllactate, owing to inhibition of the hepatic enzyme 4-hydroxyphenylpyruvate dioxygenase. The corneal lesions resemble those seen when rats are fed a diet supplemented with tyrosine, leading us to conclude that the ocular toxicity seen with NTBC is a consequence of a marked and sustained tyrosinaemia. Studies in collaboration with Professor Sven Lindstedt showed that NTBC was a potent inhibitor of purified human liver 4-hydroxyphenylpyruvate dioxygenase. This interaction lead to the concept of using NTBC to treat patients with tyrosinaemia type 1, to block or reduce the formation of toxic metabolites such as succinylacetoacetate in the liver. Zeneca Agrochemicals and Zeneca Pharmaceuticals made NTBC available for clinical use and, with the approval of the Swedish Medical Products Agency, a seriously ill child with an acute form of tyrosinaemia type 1 was successfully treated in February 1991. Subsequently, other children with this inborn error of metabolism in Sweden and other countries have been treated with NTBC. The drug is now available to those in need via Swedish Orphan AB.

The effect of a low-protein diet and dietary supplementation of threonine on tyrosine and 2-(2-nitro-4-trifluoromethylbenzoyl) cyclohexane-1,3-dione-induced corneal lesions, the extent of tyrosinemia, and the activity of enzymes involved in tyrosine catabolism in the rat.

Rats fed a low-protein diet and administered 2-(2-nitro-4-trifluoromethylbenzoyl)cyclohexane-1,3-dione (NTBC) orally at 30 mumol/kg/day (10 mg/kg/day) or fed a low-protein diet containing 5 ppm NTBC develop lesions to the cornea of the eye within 3-8 days of exposure with an incidence of about 80%. This treatment also produces a marked inhibition of both hepatic and renal 4-hydroxyphenylpyruvate dioxygenase (HPPD) activity, an induction of hepatic but not renal tyrosine amino transferase activity, and a marked tyrosinemia in the plasma and aqueous humor. The extent of tyrosinemia and changes in the activity of tyrosine catabolic enzymes are similar to those reported for rats fed a normal protein diet and administered NTBC orally at 30 mumol/kg/day. However, the onset of corneal lesions occurs much earlier in rats fed a low-protein diet. The adverse ocular effects of NTBC can be alleviated by supplementing the low-protein diet with 1% w/w threonine. The protection afforded by threonine inclusion in the diet was not due to any amelioration in the extent of inhibition of hepatic HPPD activity or reduction in the extent of the tyrosinemia as measured 8 days after treatment. Rats fed L-tyrosine at 5% w/w in a low-protein diet rapidly develop lesions to the cornea of the eye, which are associated with a marked tyrosinemia, increased hepatic tyrosine aminotransferase activity, and about a 50% reduction in the activity of hepatic HPPD. The onset of corneal lesions produced by feeding a high tyrosine diet could be delayed, but not prevented, by inclusion of 1% w/w threonine in the low-protein diet. The basis for the beneficial effect of dietary supplementation of threonine in alleviating the corneal lesions produced by NTBC is unclear. However, our findings do illustrate that protein deficiency limits the ability of the rat to respond to a tyrosine load produced by inhibition of HPPD.

Factors affecting home delivery in the Kathmandu Valley, Nepal.

This nested case-control study compares the characteristics of mothers having home or institutional deliveries in Kathmandu, Nepal, and explores the reasons given by mothers for a home delivery. The delivery patterns of mothers were identified in a cross-sectional survey of two communities: an urban area of central Kathmandu (Kalimati) and a peri-urban area (Kirtipur and Panga) five kilometres from the city centre. 357 pregnant women were identified from a survey of 6130 households: 183 from 3663 households in Kirtipur and Panga, 174 from 2467 households in Kalimati. Methods involved a structured baseline household questionnaire and detailed follow-up of identified pregnant women with structured and semi-structured interviews in hospital and the community. The main outcome measures were social and economic household details of pregnant women; pregnancy and obstetric details; place of delivery; delivery attendant; and reasons given for home delivery. The delivery place of 334/357 (94%) of the pregnant women identified at the survey was determined. 272 (81%) had an institutional delivery and 62 (19%) delivered at home. In univariate analysis comparing home and institutional deliverers, maternal education, parity, and poverty indicators (income, size of house, ownership of house) were associated with place of delivery. After multivariate analysis, low maternal educational level (no education, OR 5.04 [95% CI 1.61-15.8], class 1-10, OR 3.36 [1.04-10.8] compared to those with higher education) and multiparity (OR 3.1 [1.63-5.74] compared to primiparity) were significant risk factors for a home delivery. Of home deliverers, only 24% used a traditional birth attendant, and over half were unplanned due to precipitate labour or lack of transport. We conclude that poor education and multiparity rather than poverty per se increase the risk of a home delivery in Kathmandu. Training TBAs in this setting would probably not be cost-effective. Community-based midwife-run delivery units could reduce the incidence of unplanned home deliveries.