Engineering new limits to magnetostriction through metastability in iron-gallium alloys.

Magnetostrictive materials transduce magnetic and mechanical energies and when combined with piezoelectric elements, evoke magnetoelectric transduction for high-sensitivity magnetic field sensors and energy-efficient beyond-CMOS technologies. The dearth of ductile, rare-earth-free materials with high magnetostrictive coefficients motivates the discovery of superior materials. Fe1-xGax alloys are amongst the highest performing rare-earth-free magnetostrictive materials; however, magnetostriction becomes sharply suppressed beyond x = 19% due to the formation of a parasitic ordered intermetallic phase. Here, we harness epitaxy to extend the stability of the BCC Fe1-xGax alloy to gallium compositions as high as x = 30% and in so doing dramatically boost the magnetostriction by as much as 10x relative to the bulk and 2x larger than canonical rare-earth based magnetostrictors. A Fe1-xGax - [Pb(Mg1/3Nb2/3)O3]0.7-[PbTiO3]0.3 (PMN-PT) composite magnetoelectric shows robust 90° electrical switching of magnetic anisotropy and a converse magnetoelectric coefficient of 2.0 × 10-5 s m-1. When optimally scaled, this high coefficient implies stable switching at ~80 aJ per bit.

Mechanical spin control of nitrogen-vacancy centers in diamond.

We demonstrate direct coupling between phonons and diamond nitrogen-vacancy (NV) center spins by driving spin transitions with mechanically generated harmonic strain at room temperature. The amplitude of the mechanically driven spin signal varies with the spatial periodicity of the stress standing wave within the diamond substrate, verifying that we drive NV center spins mechanically. These spin-phonon interactions could offer a route to quantum spin control of magnetically forbidden transitions, which would enhance NV-based quantum metrology, grant access to direct transitions between all of the spin-1 quantum states of the NV center, and provide a platform to study spin-phonon interactions at the level of a few interacting spins.

Basic fibroblast growth factor inhibits cell proliferation in cultured avian inner ear sensory epithelia.

Postembryonic production of inner ear hair cells occurs after insult in nonmammalian vertebrates. Recent studies suggest that the fibroblast family of growth factors may play a role in stimulating cell proliferation in mature inner ear sensory epithelium. Effects of acidic fibroblast growth factor (FGF-1) and basic fibroblast growth factor (FGF-2) were tested on progenitor cell division in cultured auditory and vestibular sensory epithelia taken from posthatch chickens. The effects of heparin, a glycosaminoglycan that often potentiates the effects of the FGFs, were also assessed. Tritiated-thymidine autoradiographic techniques and 5-bromo-2;-deoxyuridine (BrdU) immunocytochemistry were used to identify cells synthesizing DNA. The terminal deoxynucleotidyl transferase (TdT)-mediated deoxyuridine triphosphate (dUTP)-biotin nick-end-label (TUNEL) method was used to identify apoptotic cells. TUNEL and overall counts of sensory epithelial cell density were used to assess possible cytotoxic effects of the growth factors. FGF-2 inhibited DNA synthesis in vestibular and auditory sensory epithelia and was not cytotoxic at the concentrations employed. FGF-1 did not significantly alter sensory epithelial cell proliferation. Heparin by itself inhibited DNA synthesis in the vestibular sensory epithelia and failed to potentiate the effects of FGF-1 or FGF-2. Heparin was not cytotoxic at the concentrations employed. Results presented here suggest that FGF-2 may be involved in inhibiting cell proliferation or stimulating precursor cell differentiation in avian inner ear sensory epithelia.

Fulminant hepatic failure: etiology, viral markers and outcome.

OBJECTIVE: To investigate the etiology and outcome of fulminant hepatic failure (FHF) in children. SETTING: Hospital based descriptive. METHODS: 36 children (22 males and 14 females) presenting with FHF over a period of one year were investigated. The ages ranged from 1.5 to 9 years. FHF was defined as occurrence of encephalopathy within eight weeks of onset of jaundice with no evidence of pre-existing liver disease. Detailed history, clinical examination, routine biochemical parameters and relevant diagnostic tests were carried out. Viral markers studied were anti HAV-IgM, HBsAg, anti HBc-IgM, anti-HCV and anti HEV-IgM. RESULTS: A viral etiology could be established in 22 children (61.1%). Hepatitis A (n = 12), Hepatitis B (n = 3), Hepatitis A and B (n = 2), and Hepatitis A and E (n = 4). Two children had enteric fever (1 with associated HEV), 2 children had Wilson's disease, 1 child had Indian Childhood Cirrhosis (ICC) and 2 children had drug induced hepatitis. Etiological diagnosis was not possible in 8 children (22%). Fourteen children (39%) died. Poor outcome was associated with spontaneous bleeding, raised prothrombin time, lower transaminases and higher bilirubin on admission. CONCLUSION: Viral hepatitis is the commonest cause of FHF in children. HAV alone or in combination is responsible for upto 50% of all FHF in children. Chronic liver disease can also present as FHF. Etiological diagnosis is not possible to upto one-fourth of all cases.

Macrophage and microglia-like cells in the avian inner ear.

Recent studies suggest that macrophages may influence early stages of the process of hair cell regeneration in lateral line neuromasts; numbers of macrophages were observed to increase prior to increases in hair cell progenitor proliferation, and macrophages have the potential to secrete mitogenic growth factors. We examined whether increases in the number of leukocytes present in the in vivo avian inner ear precede the proliferation of hair cell precursors following aminoglycoside insult. Bromodeoxyuridine (BrdU) immunohistochemistry was used to identify proliferating cells in chicken auditory and vestibular sensory receptor epithelia. LT40, an antibody to the avian homologue of common leukocyte antigen CD45, was used to label leukocytes within the receptor epithelia. Macrophages and, surprisingly, microglia-like cells are present in normal auditory and vestibular sensory epithelia. After hair cell loss caused by treatment with aminoglycosides, numbers of macrophage and microglia-like cells increase in the sensory epithelium. The increase in macrophage and microglia-like cell numbers precedes a significant increase in sensory epithelial cell proliferation. The results suggest that macrophage and microglia-like cells may play a role in releasing early signals for cell cycle progression in damaged inner ear sensory epithelium.

Long term survival in Indian childhood cirrhosis treated with D-penicillamine.

Indian childhood cirrhosis (ICC) is an almost uniformly fatal disease whose outcome may be modified with penicillamine if given at a sufficiently early stage. Twenty nine children with ICC seen in Pune, India, in 1980-7, who had survived at least five years from onset of penicillamine treatment, were reviewed aged 6.3 to 13 years. They were assessed clinically, biochemically, histologically, and by duplex Doppler ultrasound examination. None had symptoms suggestive of liver disease. There were no toxic effects of penicillamine other than asymptomatic proteinuria. Hepatosplenomegaly reduced significantly and liver function tests returned to normal in all. In four children, significant hepatosplenomegaly was associated with an abnormal duplex Doppler hepatic vein flow pattern and micronodular cirrhosis on biopsy. Clinical findings, growth and development, and ultrasound examination were normal in the remainder. Review of serial liver biopsy specimens showed a sequence of recovery from ICC through inactive micronodular cirrhosis to virtually normal histological appearances. The four children who still have micronodular cirrhosis beyond four years from onset remain on penicillamine treatment. In the others penicillamine was stopped after 1-7 (mean 3.5) years without relapse, strong evidence that ICC is not due to an inborn error of copper metabolism.

Cell cycle progression in gentamicin-damaged avian cochleas.

Hair cells, the sensory receptors of the auditory, vestibular, and lateral-line organs, may be damaged by a number of agents including aminoglycoside antibiotics and severe overstimulation. In the avian cochlea, lost hair cells can be replaced by regeneration. These new hair cells appear to be derived from a support cell precursor which is stimulated to divide by events associated with hair cell loss. Little is known about the timing and sequencing of events leading to new hair cell production. In this study cell cycle-associated events in the avian cochlea were analyzed at early and late time intervals following a single high dose of gentamicin. This single dose protocol has been shown to consistently result in extensive morphological damage and hair cell loss in the proximal region of the cochlea while sparing a morphologically undamaged distal cochlear region. This allowed for the differential analysis of the underlying support cell populations with respect to local hair cell loss. Three cell cycle associated markers were used to evaluate which cells entered and progressed through the cell cycle: statin, a G0 associated nuclear marker; proliferating cell nuclear antigen (PCNA), a G1, S and G2 associated marker; and 5-bromodeoxyuridine (BrdU), an S phase associated marker. Using these markers we found evidence for reversible changes in cell cycle status throughout the cochlea, while progression through S phase and mitosis was restricted to the region of the cochlea which sustained hair cell loss.

Parenteral nutrition (PN) in the management of very low birth weight (VLBW) babies--a randomized controlled trial.

Eighty five very low birth weight (VLBW) babies with birthweight less than 1250 g were randomly assigned such that 43 received parenteral nutrition (PN) with amino acid based glucose electrolyte solution (Vamin) and lipid emulsion (Intralipid) in the first 16 days of life. The other 42 (control group) received conventional intravenous dextrose with or without electrolytes plus enteral milk regimen. Baseline clinical parameters and neonatal problems encountered in the two groups were similar. There was no significant difference in the mortality rate in the two groups (48.9% in PN group and 42.9% in control group: X2 = 0.3, p > 0.05). The commonest cause of mortality in both the groups was septicemia (16.3% and 26.1% in PN and control groups, respectively). Local complications, sepsis and fluid electrolyte disturbances were similar in the two groups. Azotemia (25.6%), hyperlipidemia (9.3%), metabolic acidosis (9.3%) and prolonged cholestasis (14%) were commoner in the PN group but were reversible with early recognition. Time taken to regain birthweight was also similar in the two groups (X2 = 14.2 and 15.2 days for PN and control groups, respectively). Thus, PN failed to improve the survival or early weight gain in the routine management of the VLBW babies in our unit.

Reversal of Indian childhood cirrhosis by D-penicillamine therapy.

Serial liver biopsy changes have been reviewed in 30 patients with Indian childhood cirrhosis (ICC) who were randomly allocated to receive treatment with penicillamine in a dose of 20 mg/kg/day, 10 of whom also received prednisolone, and five receiving placebo. The latter died within 185 (mean, 149) days of starting treatment. Nine receiving penicillamine died within 540 (mean, 338) days, but the remainder are well 5.1-9.3 years after commencing treatment. Initial biopsies showed severe hepatocellular injury, pericellular fibrosis, inflammatory infiltration, and orcein-staining granules. Second biopsies taken within 6 months of starting penicillamine usually showed persistence of inflammation and an increase in nodularity with thick and thin active septae. Subsequently the appearances were of an inactive micronodular cirrhosis, with reduction in septal inflammatory infiltrate, hepatocellular injury, and intensity of orcein staining. This further improved to a stage of incomplete fibrous septae. The last liver biopsies at 6-60 months (in 21 survivors) showed almost normal histology in four, incomplete fibrous septae in five, and inactive micronodular cirrhosis with thin septae in 12. Mean liver copper concentrations decreased from 1,407 (SEM, 121) micrograms/g at presentation to 925 (183), 317 (100), and 127 (35) at 6, 6-18, and > 18 months after starting treatment. By contrast, a second biopsy taken in the 6 months after diagnosis in placebo-treated children showed persistence of ICC with increase in inflammation, fibrosis, and orcein staining.

Catch up growth and its determinants in low birth weight babies: a study using Z scores.

Two hundred and forty seven low birthweight (LBW) survivors of our Neonatal Intensive Care Unit and 164 normal birthweight controls were followed up longitudinally from birth to 4 years and their growth trends (weight, height, head circumference) were expressed as mean Z scores in 500 g birthweight categories. Whereas LBW's demonstrated rapid growth in the first 6 months of life, followed by generally parallel trends with some tendency to rise, controls showed distinct growth faltering especially after one year. Only 30.8% of LBWs (and 49% of controls) were within the designated catch up levels for weight by age 4 years. The corresponding number for catch up of height and head circumference in LBW's was 22.8% and 26.5%, respectively. On multiple regression analysis, the most important determinants of catch up (at 4 years) in LBW's were weight at 1 year (beta = 0.51), height at 1 year (beta = 0.31) and mother's weight (beta = 0.04). Thus, Z scores enabled the demonstration of changing growth trends, simultaneous comparisons with local controls and international standards and comparison within indices. Growth charts incorporating Z score should be made available in a simplified manner for use in the community.

Vegetable oil fortified feeds in the nutrition of very low birthweight babies.

Two kinds of oils (i) Polyunsaturated fatty acids (PUFA) rich Safflower oil, and (ii) Medium chain triglyceride (MCT) rich Coconut oil were added to the feeds of 46 very low birthweight (VLBW) babies to see if such a supplementation is capable of enhancing their weight gain. Twenty two well matched babies who received no fortification served as controls. The oil fortification raised the energy density of the feeds from approximately 67 kcal/dl to 79 kcal/dl. Feed volumes were restricted to a maximum of 200 ml/kg/day. The mean weight gain was highest and significantly higher than the controls in the Coconut oil group (19.47 +/- 8.67 g/day or 13.91 g/day). Increase in the triceps skinfold thickness and serum triglycerides were also correspondingly higher in this group. The lead in the weight gain in this group continued in the follow up period (corrected age 3 months). As against this, higher weight gain in Safflower oil group (13.26 +/- 6.58 g/day) as compared to the controls (11.59 +/- 5.33 g/day), failed to reach statistically significant proportions, probably because of increased statistically significant proportions, probably because of increased steatorrhea (stool fat 4+ in 50% of the samples tested). The differences in the two oil groups are presumably because of better absorption of MCT rich coconut oil. However, individual variations in weight gain amongst the babies were wide so that some control babies had higher growth rates than oil fortified ones. The technique of oil fortification is fraught with dangers of intolerance, contamination and aspiration. Long term effects of such supplementation are largely unknown.(ABSTRACT TRUNCATED AT 250 WORDS)

PIP: During a period of 12 months, polyunsaturated fatty acids (PUFA) rich safflower oil and medium chain triglyceride (MCI) rich coconut oil were added to the feeds of 46 very low birth weight (VLBW) babies (birth weight of 1250-1500 g) to see if such a supplementation could augment their weight gain. In the safflower oil fortification group, 22 babies completed the study, and in the coconut oil fortification group, 24 did. 22 babies who received no fortification served as controls. The oil fortification raised the energy density of the feeds from approximately 67 kcal/dl to 79 kcal.dl. Feed volumes were restricted to a maximum of 200 ml/kg/day. 3 babies of the safflower oil group and 2 each of the 2 other groups developed loose motions, but they all survived and completed the study. The diarrhea in the safflower oil group was related to addition of oil exceeding 0.5 ml and responded to discontinuation of oil. An increase in serum triglyceride values was seen in all 3 study groups, but the increase in the coconut oil group was significantly greater than the increase in the controls (p 0.05). The mean weight gain per day, weight gain per kg per day (19.47 +or- 8.67 g/day or 13.91 g/day), and mean weekly increment in skinfold thickness were significantly greater in the coconut oil group as compared to controls (p 0.05). The lead in the weight gain in this group continued in the follow-up period (corrected age, 3 months). Higher weight gain in the safflower oil group (13.26 +or- 6.58 g/day) as compared to the controls (11.59 +or- 5.33 g/day) failed to reach statistical significance, probably because of increased steatorrhea (stool fat 4+ in 50% of the samples tested). The differences in the 2 oil groups presumably occurred because of better absorption of MCI rich coconut oil. The technique of oil fortification is fraught with dangers because of aspiration and contamination. Accordingly, such fortification should be used in selected situations only, rather than as a routine nursery policy.

The prevention of Indian childhood cirrhosis.

Previous studies have led to the hypothesis that the gross hepatic copper storage characteristic of Indian childhood cirrhosis (ICC) is due to the early introduction of animal milk feeds which have been contaminated with copper from brass household utensils. Amongst the families of 100 cases of ICC, the incidence of ICC in children born after dietary advice had been given (1/86) was significantly lower than in older siblings (12/125). This study attempted to document the incidence of ICC and the usage of brass before and after an intervention programme in Pune District advising against this pattern of infant feeding. The study encountered numerous difficulties in data gathering, but documented a fall in ICC prevalence resulting in its virtual disappearance in Pune District. This contrasted with an unchanged incidence in Chandigarh. Although a fall in brass usage was seen in Pune District, this was actually a spontaneous sociological change rather than a result of health education.

Reduction in parenteral nutrition related complications in the newborn.

A comparison of total parenteral nutrition (TPN) related complication in newborns was made between two study periods, namely, 1986 (Study A) and 1989-90 (Study B). A significant reduction was seen in all complications in Study B. Local complications (thrombophlebitis, gangrene, abscess) reduced from 80.0 to 29.4%, septicemia from 52.0 to 11.7% and metabolic complications from a computed mean of 1.6 episode per baby to 0.88 episode per baby. The reduction in these complications has been attributed to the following additional inputs in the recent study (i) Additional staff (research officers, nurses, biochemist); (ii) Better training of resident staff; (iii) Use of a laminar flow system for mixing solutions; (iv) Specially designed locally manufactured intravenous sets and accessories; and (v) Use of well balanced nutrient solutions. Outstanding problems perceived are--high incidence of TPN-related cholestasis (14.7%), azotemia (26.4%), central catheter-related sepsis (75.0%) and the falling, but yet high cost of the technique (Rs. 650 per day).

Trends in perinatal and neonatal mortality and morbidity in India.

Although the infant mortality rate (IMR) has reduced by 50% during the past century, it compares poorly with the advanced countries and some developing countries. The observed fall in IMR has been mostly in post-neonatal mortality, with the result that neonatal deaths now account for over 60% of all infant deaths. The overall perinatal mortality rate (PMR) in India is still over 50 per 1000 and has shown virtually no decline during the past decade, However, PMR differs widely in different states, urban/rural areas, different hospitals and so on. PMR is seen to correlate better with social development than economic development of the representative community. The causes of perinatal deaths suggest poor health of mother and poor health facilities and are hence potentially preventable. Various studies have shown that PMR can be significantly reduced within a short span of time. The registration of vital statistics continue to be highly unsatisfactory especially in rural areas.

PIP: Although the infant mortality rate (IMR) in India has been reduced by 50% over the past century, it compares poorly with the developed countries and with some developing countries. The observed fall in IMR has been the result of change in postneonatal mortality with the result that neonatal deaths now account for over 60% of all infant deaths. The overall perinatal mortality rate (PMR) in India is still over 50/1000 and has shown virtually no decline during the past decade. However, PMR differs widely in different states, urban/rural areas, different hospitals, etc. PMR is seen to correlate better with social development that economic development of the representative community. The causes of perinatal deaths suggest poor health of the mother and poor health facilities and are therefore potentially preventable. Various studies have shown that PMR can be significantly reduced within a short span of time. The registration of vital statistics continues to be highly unsatisfactory, especially in rural areas.

Copper in urine and hair in Indian childhood cirrhosis.

In advanced Indian childhood cirrhosis (ICC) urine copper concentration was higher (range 416-103,448 mg/g creatinine) than in other hepatic diseases (range 67-10,303 mg/g creatinine). In early ICC urine copper concentration was more modestly raised (1188-9470 mg/g creatinine), but rose to high values (2222-42,819 mg/g creatinine) after a single dose of penicillamine 20 mg/kg. A post-penicillamine urinary copper:creatinine ratio greater than 10,000 mg/g supports a diagnosis of ICC. The concentration of copper in the hair, while increased in advanced ICC, is of no diagnostic value in early cases.

Clinical trials of penicillamine in Indian childhood cirrhosis.

The outcome in 15 children with advanced Indian childhood cirrhosis (ICC) treated with penicillamine 20 mg/kg/day was not significantly different from that in untreated children. Among children admitted to a further double blind trial who had ICC but who had not yet developed jaundice or ascites 10 treated with penicillamine and 10 treated with penicillamine plus prednisolone had a significantly improved survival. Fourteen of 29 treated cases made a clinical recovery and were alive 489 to 1460 days from the start of treatment. Biopsy specimens in survivors showed a return to normal liver histology in three, residual fibrosis in six, and inactive micronodular cirrhosis in five. Thus penicillamine, while not shown to be beneficial in advanced ICC, lowered mortality from 93% to 52% in preicteric cases of ICC.

Comparison of feeding history of children with Indian childhood cirrhosis and paired controls.

One hundred prospectively studied children with Indian childhood cirrhosis (ICC) in Pune District, India, differed from 100 matched controls with respect to feeding history. Animal milk was used in all ICC cases but not in 27 controls. It had been started by 3 months in 63 cases and by 6 months in 82 cases of ICC, as compared with 15 and 25 controls. Twenty-four ICC cases received no breast feeding, and 45 and 60 were breast fed for less than 3 and less than 6 months, respectively; only 10 control children were breast fed for less than 6 months. All ICC children's feeds had been in contact with brass vessels. Copper vessels were used for water carriage with equal frequency in cases and controls. Girls predominated amongst healthy older siblings of cases. Ninety-one healthy siblings of cases had been fed similarly to controls. Three pairs of twins with similar feeding histories died with ICC, whereas two pairs were discordant for feeding and outcome. Hepatic copper loading in ICC is attributable to copper contamination of early animal milk feeds.