Effects of motion and audio-visual redundancy on upright and inverted face and feature preferences in 4-13-month old pre- and full-term NICU graduates.

NICU infants are reported to have diminished social orientation and increased risk of socio-communicative disorders. In this eye tracking study, we used a preference for upright compared to inverted faces as a gauge of social interest in high medical risk full- and pre-term NICU infants. We examined the effects of facial motion and audio-visual redundancy on face and eye/mouth preferences across the first year. Upright and inverted baby faces were simultaneously presented in a paired-preference paradigm with motion and synchronized vocalization varied. NICU risk factors including birth weight, sex, and degree of CNS injury were examined. Overall, infants preferred the more socially salient upright faces, making this the first report, to our knowledge, of an upright compared to inverted face preference among high medical risk NICU infants. Infants with abnormalities on cranial ultrasound displayed lower social interest, i.e. less of a preferential interest in upright faces, when viewing static faces. However, motion selectively increased their upright face looking time to a level equal that of infants in other CNS injury groups. We also observed an age-related sex effect suggesting higher risk in NICU males. Females increased their attention to the mouth in upright faces across the first year, especially between 7-10 months, but males did not. Although vocalization increased diffuse attention toward the screen, contrary to our predictions, there was no evidence that the audio-visual redundancy embodied in a vocalizing face focused additional attention on upright faces or mouths. This unexpected result may suggest a vulnerability in response to talking faces among NICU infants that could potentially affect later verbal and socio-communicative development.

Gut microbiome modulates response to anti-PD-1 immunotherapy in melanoma patients.

Preclinical mouse models suggest that the gut microbiome modulates tumor response to checkpoint blockade immunotherapy; however, this has not been well-characterized in human cancer patients. Here we examined the oral and gut microbiome of melanoma patients undergoing anti-programmed cell death 1 protein (PD-1) immunotherapy (n = 112). Significant differences were observed in the diversity and composition of the patient gut microbiome of responders versus nonresponders. Analysis of patient fecal microbiome samples (n = 43, 30 responders, 13 nonresponders) showed significantly higher alpha diversity (P < 0.01) and relative abundance of bacteria of the Ruminococcaceae family (P < 0.01) in responding patients. Metagenomic studies revealed functional differences in gut bacteria in responders, including enrichment of anabolic pathways. Immune profiling suggested enhanced systemic and antitumor immunity in responding patients with a favorable gut microbiome as well as in germ-free mice receiving fecal transplants from responding patients. Together, these data have important implications for the treatment of melanoma patients with immune checkpoint inhibitors.

Pancreas-After-Islet Transplantation in Nonuremic Type 1 Diabetes: A Strategy for Restoring Durable Insulin Independence.

Islet transplantation offers a minimally invasive approach for ß cell replacement in diabetic patients with hypoglycemic unawareness. Attempts at insulin independence may require multiple islet reinfusions from distinct donors, increasing the risk of allogeneic sensitization. Currently, solid organ pancreas transplant is the only remaining surgical option following failed islet transplantation in the United States; however, the immunologic impact of repeated exposure to donor antigens on subsequent pancreas transplantation is unclear. We describe a case series of seven patients undergoing solid organ pancreas transplant following islet graft failure with long-term follow-up of pancreatic graft survival and renal function. Despite highly variable panel reactive antibody levels prior to pancreas transplant (mean 27 ± 35%), all seven patients achieved stable and durable insulin independence with a mean follow-up of 6.7 years. Mean hemoglobin A1c values improved significantly from postislet, prepancreas levels (mean 8.1 ± 1.5%) to postpancreas levels (mean 5.3 ± 0.1%; p = 0.0022). Three patients experienced acute rejection episodes that were successfully managed with thymoglobulin and methylprednisolone, and none of these preuremic type 1 diabetic recipients developed stage 4 or 5 chronic kidney disease postoperatively. These results support pancreas-after-islet transplantation with aggressive immunosuppression and protocol biopsies as a viable strategy to restore insulin independence after islet graft failure.

Fine social aspiration: Twitter as a voice for cytopathology.

Social media is an influential tool that has the power to transform cytopathology. Twitter is being used more and more to share cutting-edge updates from pathology meetings ("live-tweeting"). Modern smartphones can now take high resolution microscopic photographs and easily transmit them worldwide via Twitter, Facebook, and other social media, allowing cytopathologists to share educational pearls and discuss difficult cases on a global scale like never before. Social media also allows cytopathologists to share a behind-the-scenes look at their subspecialty with other physicians and even the non-medical public, helping them to better understand the crucial importance of cytopathology in modern medicine. This could positively impact rapport with other specialties, influence policy making, and possibly even improve delivery of patient care. Rare disease patient communities are being formed by patients on Facebook. By joining and volunteering with these patient groups, cytopathologists would have further opportunity to interact directly with patients and their family members, explaining the role of cytopathology in patient care and helping patients to better understand their own diseases. Social media enables cytopathologists and their colleagues in other pathology subspecialties to easily and rapidly form a broad and diverse worldwide network with one another. The authors believe that this is the key to a bright future for our specialty, a strong unified global community of pathologists all working together for education, patient advocacy, and outstanding patient care. Social media can allow us to build that community, strengthen its bonds, and harness its power like never before in history. Diagn. Cytopathol. 2017;45:705-713. © 2017 Wiley Periodicals, Inc.

Metallothionein as a clonable tag for protein localization by electron microscopy of cells.

A benign, clonable tag for the localization of proteins by electron microscopy of cells would be valuable, especially if it provided labelling with high signal-to-noise ratio and good spatial resolution. Here we explore the use of metallothionein as such a localization marker. We have achieved good success with desmin labelled in vitro and with a component of the yeast spindle pole body labelled in cells. Heavy metals added after fixation and embedding or during the process of freeze-substitution fixation provide readily visible signals with no concern that the heavy atoms are affecting the behaviour of the protein in its physiological environment. However, our methods did not work with protein components of the nuclear pore complex, suggesting that this approach is not yet universally applicable. We provide a full description of our optimal labelling conditions and other conditions tried, hoping that our work will allow others to label their own proteins of interest and/or improve on the methods we have defined.

Vascular neoplasm or pseudovascular nevus? Potential pitfalls in diagnosis.

Melanocytic nevi, on histopathologic evaluation, occasionally contain slit-like clefts or spaces that may resemble vascular or lymphatic spaces. The spaces may contain blood or, perhaps more concerning, nests of melanocytes that could suggest lymphatic invasion of melanoma. When lined by melanocytes rather than true endothelium, these pseudovascular spaces within melanocytic nevi are generally attributable to tissue processing artifact. When the space in question is pronounced, a proper diagnostic work-up is prudent in order to exclude a true vascular neoplasm or melanoma. In this case series we present several melanocytic lesions with prominent vascular-appearing spaces that warranted further investigation.

Determinants of aggressive and prosocial behaviour among Jamaican schoolboys.

PURPOSE: This study examines risk factors for aggression among boys in Kingston, Jamaica. METHODS: One hundred and one aggressive and 101 prosocial schoolboys in grades 5-6 (mean age 11.7, SD 0.6 years) were selected by peer and teacher ratings from 10 schools in the capital city, Kingston, during 1998. They were given in-depth questionnaires, arithmetic, reading and verbal intelligence tests and their behaviour was rated. Their parents were also given a detailed questionnaire. RESULTS: The aggressive boys reported significantly more involvement in fights than the prosocial boys. They had lower scores on spelling/reading and verbal IQ, less ambitious aspirations and poorer quality school uniforms. They were not more likely to infer hostile intent in ambiguous situations but were more likely to respond with aggression. Aggressive boys came from poorer homes with more marijuana use, less parental affection or supervision and more family discord. They were less exposed to religious instruction, their parents had lower occupational levels and were more likely to be in common-law unions than married. They were more exposed to neighbourhood violence and were punished more often at home and at school. Logistic regression analyses were carried out to determine the independent risk factors for aggression. Exposure to neighbourhood violence, physical punishment at home and family discord were associated with increased risk; parents' being married, practising religion as a family and better school uniforms were associated with reduced risk. CONCLUSIONS: Although community violence was a serious problem, family characteristics were also important risk factors for aggressive behaviour.

Determinants of aggressive and prosocial behaviour among Jamaican schoolboys / Determinantes del comportamiento agresivo y prosocial entre los escolares Jamaicanos)

PURPOSE: This study examines risk factors for aggression among boys in Kingston, Jamaica. METHODS: One hundred and one aggressive and 101 prosocial schoolboys in grades 5-6 (mean age 11.7, SD 0.6 years) were selected by peer and teacher ratings from 10 schools in the capital city, Kingston, during 1998. They were given in-depth questionnaires, arithmetic, reading and verbal intelligence tests and their behaviour was rated. Their parents were also given a detailed questionnaire. RESULTS: The aggressive boys reported significantly more involvement in fights than the prosocial boys. They had lower scores on spelling/reading and verbal IQ, less ambitious aspirations and poorer quality school uniforms. They were not more likely to infer hostile intent in ambiguous situations but were more likely to respond with aggression. Aggressive boys came from poorer homes with more marijuana use, less parental affection or supervision and more family discord. They were less exposed to religious instruction, their parents had lower occupational levels and were more likely to be in common-law unions than married. They were more exposed to neighbourhood violence and were punished more often at home and at school. Logistic regression analyses were carried out to determine the independent risk factors for aggression. Exposure to neighbourhood violence, physical punishment at home and family discord were associated with increased risk; parents' being married, practising religion as a family and better school uniforms were associated with reduced risk. CONCLUSIONS: Although community violence was a serious problem, family characteristics were also important risk factors for aggressive behaviour.

Propósito: Este estudio examina los factores de riesgo que influyen en la agresión entre los niños en Kingston, Jamaica. Métodos: Ciento un escolares agresivos y 101 escolares prosociales en los grados 5­6 (edad promedio 11.7, desviación estándard 0.6 años) fueron seleccionados de acuerdo con las valoraciones de los pares y los maestros de 10 escuelas en la ciudad capital, Kingston, durante 1998. Se les aplicó cuestionarios exhaustivos, así como pruebas de aritmética y lectura, tests de inteligencia, y se clasificó su conducta. A sus padres también se les aplicó un cuestionario detallado. Resultados: Los niños agresivos reportaron una participación en peleas significativamente mayor que los niños prosociales. Asimismo, tuvieron puntuaciones más bajas en deletreo, lectura y coeficiente de inteligencia (C.I.) verbal, mostraron tener aspiraciones menos ambiciosas, y vestían uniformes más pobres. No estaban más inclinados a inferir intenciones hostiles en situaciones ambiguas, pero si más propensos a responder agresivamente. Los niños agresivos provenían de hogares más pobres, caracterizados por mayor consumo de marihuana, menos afecto o supervisión por parte de los padres, y más discordia en la familia. Estaban también menos expuestos a la instrucción religiosa, sus padres tenían bajo nivel ocupacional, y vivían en su mayor parte más en unión consensual que en matrimonio. Estaban más expuestos a la violencia del vecindario, y recibían castigos en la casa y la escuela con mayor frecuencia. Se llevaron a cabo análisis de regresión logística a fin de determinar los factores de riesgo de la agresión. La exposición a la violencia del vecindario, el castigo físico en el hogar, y la discordia familiar estaban asociados con el aumento del riesgo. En cambio, padres casados en matrimonio, la práctica de la religión como familia, y mejores uniformes escolares, estuvieron asociados con la reducción del riesgo. Conclusiones. Aunque la violencia comunitaria constituía un serio problema, las características de la familia fueron también importantes factores de riesgo en el comportamiento agresivo.

Effect of accommodating sucking and nosing on the behaviour of artificially reared piglets.

Neonatal piglets are often used in biomedical research applications that require artificial rearing. Social housing can be problematic because the piglets develop belly nosing, navel and ear sucking that can result in injury. Our objective was to determine the effectiveness of using feeding devices that provide various opportunities for sucking and nosing behaviour on reducing piglet-directed behaviour of group-housed laboratory piglets. Fifteen piglets were used in each of four trials. The piglets nursed their dam for approximately 72 h to obtain passive immunity before transfer to a laboratory facility where they were allotted, five per group, to one of three stainless steel isolator units. Each unit featured a different style of feeding system for the delivery of milk replacer: a plastic trough (T), a nipple (N) mounted on a smooth plexiglass wall, or a nipple mounted on a pliant bag of sterile water (artificial udder [AU]). Each system had five feeding spaces so that all piglets fed simultaneously. Milk was provided at 6-h intervals, and behaviour was recorded on alternate days for 12 days post-weaning. Although trough-fed piglets began to eat much sooner than those piglets fed from nipples, time spent nosing, chewing or sucking on pen-mates and belly nosing were markedly higher in T piglets than in either N or AU, overall (mean: P<0.05) and over time (quadratic: P<0.05). Over time, N piglets developed a stereotypic snout rubbing on the wall behind the nipples, while AU piglets massaged and often fell asleep in contact with the udder from day 2 of the trial. Resting patterns were also affected. N and AU piglets settled down to rest more quickly (P<0.01) and spent significantly more time resting in the hour following feeding than T piglets (P<0.05). A feeding device that accommodates both sucking and massage can significantly reduce piglet-directed behaviour and may facilitate social housing of artificially reared piglets.

Breastfeeding patterns among six-week-old term infants at the University Hospital of the West Indies / Patrones de Lactancia Materna entre los Infantes de Seis Semanas en el Hospital Universitario de West Indies

Eighty-nine mothers attending post-natal clinics at the University Hospital of the West Indies were interviewed at six weeks postpartum regarding their breast-feeding patterns and problems. Breastfeeding was practised by 97.8 of the mothers, with 29.9 practising exclusive breastfeeding and 70.1 partial breastfeeding. Only two women were solely bottle feeding. The pattern of breastfeeding was not significantly affected by maternal parity, age, education, employment or socioeconomic status. An intention to wean later (at six months) or when the mother felt the baby was 'ready,' was associated with increasing parity, age and further education. Babies who were exclusively breastfed achieved greater weight gain compared with those who partially breastfed but this difference did not achieve statistical significance. Breastfeeding trends appear to have remained stable over the last several years

Ochenta y nueve madres que asistían a las clínicas de atención postnatal en el Hospital Universitario de West Indies fueron entrevistadas seis semanas después del parto, en relación con los problemas y patrones de lactancia al pecho. El amamantamiento era practicado por el 97.8% de las madres, un 29.9% de las cuales practicaba la lactancia materna exclusivamente, en tanto el 70.1% la practicaba de modo parcial. Sólo dos mujeres recurrían a la alimentación sólo por biberón. El patrón de lactancia materna no era afectado significativamente por paridad materna, edad, educación, empleo o estatus socio-económico. La intención de destetar más tarde (a los seis meses) o cuando la madre sentía que el bebé estaba "listo", se hallaba asociada con un grado creciente de paridad, edad y educación continuada. Los recién nacidos que recibieron exclusivamente lactancia materna alcanzaron un peso mayor en comparación con aquéllos que recibieron lactancia al pecho parcial, pero esta diferencia no llegó a tener significación estadística. Las tendencias a la lactancia materna parecen haber permanecido estables durante los últimos años

Mutations in the human orthologue of the mouse underwhite gene (uw) underlie a new form of oculocutaneous albinism, OCA4.

Oculocutaneous albinism (OCA) affects approximately 1/20,000 people worldwide. All forms of OCA exhibit generalized hypopigmentation. Reduced pigmentation during eye development results in misrouting of the optic nerves, nystagmus, alternating strabismus, and reduced visual acuity. Loss of pigmentation in the skin leads to an increased risk for skin cancer. Two common forms and one infrequent form of OCA have been described. OCA1 (MIM 203100) is associated with mutations of the TYR gene encoding tyrosinase (the rate-limiting enzyme in the production of melanin pigment) and accounts for approximately 40% of OCA worldwide. OCA2 (MIM 203200), the most common form of OCA, is associated with mutations of the P gene and accounts for approximately 50% of OCA worldwide. OCA3 (MIM 203290), a rare form of OCA and also known as "rufous/red albinism," is associated with mutations in TYRP1 (encoding tyrosinase-related protein 1). Analysis of the TYR and P genes in patients with OCA suggests that other genes may be associated with OCA. We have identified the mouse underwhite gene (uw) and its human orthologue, which underlies a new form of human OCA, termed "OCA4." The encoded protein, MATP (for "membrane-associated transporter protein") is predicted to span the membrane 12 times and likely functions as a transporter.

Belly-nosing in early-weaned piglets is not influenced by diet quality or the presence of milk in the diet.

Early weaning of piglets can lead to an increase in belly-nosing and other oral-nasal behavior (nosing, chewing, or sucking other piglets), but the causative factors involved in these behavior patterns are largely unknown. Because these behavior patterns resemble massaging the udder and sucking, they may be associated with feeding. The objectives of this study were to determine any effect of diet quality or the presence of milk in the diet on belly-nosing behavior of piglets weaned at 14 to 18 d. During the first 2 wk after weaning, piglets were fed diets differing in quality and inclusion of milk products. Six replicates of eight piglets per replicate, blocked by initial body weight, (n = 192) were offered one of four dietary treatments: HQM: high quality, high in milk products; HQ: high quality, no milk products; PQ: poor quality, no milk products; HQ+MR: high quality, no milk products (as HQ) sprayed with milk replacer five times daily. Thereafter, the piglets were fed a standard nursery diet. Feed intake was measured daily for wk 1 and again at the end of wk 2. Behavior was recorded every 5 min during two 4-h periods on d 2 to 7, 10, 14, 17 and 21 after weaning. Dietary treatment influenced ADFI and ADG during wk 1. Average daily feed intake (P < 0.05) and ADG (P < 0.05) of piglets on PQ were less than those of piglets on the other treatments. During wk 2, ADFI (P > 0.10) and ADG (P > 0.10) were the same across all treatments. Overall, ADFI was not influenced by the inclusion of milk products in the diet or the addition of milk replacer (P > 0.10); however, ADG was. Piglets on HQM had higher ADG than those on HQ during wk 2 (P < 0.05) and 3 after weaning (P < 0.05). However, milk replacer did not influence ADG (P > 0.10). Although the dietary treatments did affect ADFI and ADG, there were no effects on any behavior pattern recorded, including time spent at the feeder (P > 0.10). Lower weight-for-age piglets performed more oral-nasal behavior, in total, than higher weight-for-age piglets (P < 0.03). Neither feeding a poor-quality diet nor the presence of milk in the diet had an effect on belly-nosing or other oral-nasal behavior patterns during the first 3 wk after weaning. Belly-nosing does not seem to be associated with feeding.

Therapeutic effects of oral zinc in acute and persistent diarrhea in children in developing countries: pooled analysis of randomized controlled trials.

BACKGROUND: Zinc deficiency is prevalent in children in developing countries. Supplemental zinc provides therapeutic benefits in diarrhea. OBJECTIVE: We sought to measure the effect of supplemental zinc given with oral rehydration therapy during recovery from acute or persistent diarrhea. DESIGN: We conducted pooled analyses including all available published and unpublished randomized controlled trials of the effects of supplementary oral zinc in children aged <5 y with acute or persistent diarrhea. We used Cox survival regression analysis to evaluate the overall effect of zinc on continuation of diarrhea and possible differential effects in subgroups divided by sex, age, weight-for-height, and initial plasma zinc concentration. Dichotomous outcomes were analyzed by logistic regression. To assess the effects of excluding studies without original data from the pooled analyses, effect-size was estimated for all studies by using random-effects models. RESULTS: Zinc-supplemented children had a 15% lower probability of continuing diarrhea on a given day (95% CI: 5%, 24%) in the acute-diarrhea trials and a 24% lower probability of continuing diarrhea (95% CI: 9%, 37%) and a 42% lower rate of treatment failure or death (95% CI: 10%, 63%) in the persistent-diarrhea trials. In none of the subgroup analyses were the 2 subgroups of each pair significantly different from each other; however, in persistent diarrhea there tended to be a greater effect in subjects aged <12 mo, who were male, or who had wasting or lower baseline plasma zinc concentrations. CONCLUSION: Zinc supplementation reduces the duration and severity of acute and persistent diarrhea.

Aberrant pH of melanosomes in pink-eyed dilution (p) mutant melanocytes.

In past studies, we cloned the mouse p gene and its human homolog P, which is associated with oculocutaneous albinism type 2. Both mouse and human genes are expressed in melanocytes and encode proteins predicted to have 12 membrane-spanning domains with structural homology to known ion transporters. We have also demonstrated that the p protein is localized to the melanosomal membrane and does not function as a tyrosine transporter. In this study, immunohistochemistry and confocal microscopy were used to show that the p protein plays an important role in the generation or maintenance of melanosomal pH. Melanosomes (and their precursor compartments) were defined by antiserum directed against the melanosomal marker tyrosinase related protein 1. Acidic vesicles were identified by 3-(2, 4-dinitroanilino)-3'-amino-N-methyldipropylamine incorporation, visualized with anti-dinitrophenol. In C57BL/6+/+ (wild-type) melanocytes, 94.2% of vesicles demonstrated colocalization of tyrosinase related protein 1 and 3-(2, 4-dinitroanilino)-3'-amino-N-methyldipropylamine, indicating that almost all melanosomes or their precursors were acidic. By contrast, only 7%-8% of the staining vesicles in p mutant cell lines (pJ/pJ and pcp/p6H) showed colocalization of tyrosinase related protein 1 and 3-(2,4-dinitroanilino)-3'-amino-N-methyldipropylamine. Thus, without a functional p protein, most melanosomes and their precursors are not acidic. As mammalian tyrosinase activity in situ is apparently dependent on low pH, we postulate that in the absence of a low pH environment brought about by ionic transport mediated by the p protein, tyrosinase activity is severely impaired, leading to the minimal production of melanin that is characteristic of p mutants. Additionally (or alternatively), an abnormal pH may also impair the assembly of the normal melanogenic complex.

The use of herbal teas and remedies in Jamaica.

We investigated the prevalence of the use of herbs among adults and children in Jamaica in 1996. Two concurrent surveys were conducted in randomly selected urban and rural areas: among adults and among caretakers of young children. From over 90% of the selected households, all caretakers of children under 6 years and one randomly selected adult (18 years or older) were interviewed using structured questionnaires. The 457 adults reportedly used 156 types of herbs: a mean of 6 +/- 3 (mean +/- standard deviation) by the urban adults, and 10 +/- 6 by the rural adults (t-test, p < 0.001). Almost 100% of respondents had at some time used herbs for teas or for treating illnesses. The most common method of preparation was by infusion or boiling in water, then adding sugar. Urban respondents, women and those who were employed were more likely to buy medicines than to use herbal remedies. One hundred and sixty-seven caretakers of 203 children under 6 years were interviewed. The mean number of herbs given to each child was between 2 and 3. The most common herbs were introduced within the first 6 months of life. Many caretaker factors were associated with herbal use. Public health implications include the potential toxicity of some herbs, the possibility that herbal teas given to young children may displace more nutritious foods and delay presentation to health care facilities. The findings will allow policy makers to target those most likely to use herbal preparations or to give them to young children, and target herbs to be analyzed for toxic or beneficial properties.

Prevention of diarrhea and pneumonia by zinc supplementation in children in developing countries: pooled analysis of randomized controlled trials. Zinc Investigators' Collaborative Group.

OBJECTIVES: This study assessed the effects of zinc supplementation in the prevention of diarrhea and pneumonia with the use of a pooled analysis of randomized controlled trials in children in developing countries. STUDY DESIGN: Trials included were those that provided oral supplements containing at least one half of the United States Recommended Daily Allowance (RDA) of zinc in children <5 years old and evaluated the prevention of serious infectious morbidity through household visits. Analysis included 7 "continuous" trials providing 1 to 2 RDA of elemental zinc 5 to 7 times per week throughout the period of morbidity surveillance and 3 "short-course" trials providing 2 to 4 RDA daily for 2 weeks followed by 2 to 3 months of morbidity surveillance. The effects on diarrhea and pneumonia were analyzed overall and in subgroups defined by age, baseline plasma zinc concentration, nutritional status, and sex. The analysis used random effects hierarchical models to calculate odds ratios (OR) and 95% CIs. RESULTS: For the zinc-supplemented children compared with the control group in the continuous trials, the pooled ORs for diarrheal incidence and prevalence were 0.82 (95% CI 0.72 to 0.93) and 0.75 (95% CI 0.63 to 0.88), respectively. Zinc-supplemented children had an OR of 0.59 (95% CI 0.41 to 0.83) for pneumonia. No significant differences were seen in the effects of the zinc supplement between the subgroups examined for either diarrhea or pneumonia. In the short-course trials the OR for the effects of zinc on diarrheal incidence (OR 0.89, 95% CI 0.62 to 1.28) and prevalence (OR 0.66, 95% CI 0.52 to 0.83) and pneumonia incidence (OR 0.74, 95% CI 0.40 to 1.37) were similar to those in the continuous trials. CONCLUSIONS: Zinc supplementation in children in developing countries is associated with substantial reductions in the rates of diarrhea and pneumonia, the 2 leading causes of death in these settings.

In vivo evaluation of a novel epitope-tagged human factor VIII-encoding adenoviral vector.

Haemophilia A is caused by a deficiency in coagulation factor VIII (FVIII) and is an attractive target for gene therapy. Adenoviral vectors encoding a human B-domain deleted (BDD) FVIII cDNA have been shown previously to mediate expression of high levels of human FVIII and correct the bleeding defect in haemophiliac mice and dogs. While vector assessment in a non-human primate model would have a significant preclinical benefit, a haemophiliac non-human primate model is not available, and assays that distinguish human FVIII from monkey FVIII have not been developed successfully. As a first step to enable vector evaluation in non-human primates, we have constructed an epitope-tagged FVIII molecule by the addition of 16 amino-acids to the carboxy terminus of the BDD protein (BDD-E). Following vector administration to normal mice, therapeutic levels of BDD-E FVIII were expressed for at least 20 weeks. Treatment of haemophiliac mice revealed that the BDD-E protein was biologically active in vivo. To distinguish the BDD-E protein from non-human primate FVIII, a sensitive immunoprecipitation/Western assay was developed that reproducibly detected 1 ng mL-1 of the epitope-tagged human FVIII in the presence of monkey plasma. These data demonstrate that the addition of an epitope tag had no effect on FVIII function or immunogenicity, and suggest that the BDD-E vector will be an effective reagent for non-human primate studies.

Perinatal death: uncovering the needs of midwives and nurses and exploring helpful interventions in the United States, England, and Japan.

Perinatal death is a crisis for midwives and nurses as well as for bereaved parents and extended families. Surveys and interviews conducted in the United States, England, and Japan described the needs and responses of nurses and midwives as they coped with their own feelings while caring for bereaved parents. Results emphasized common needs of caregivers for increased knowledge, mentored experience, communication skills, and personal support to confidently provide sensitive care to families. Although need for education regarding cultural-specific care was revealed, participants identified helpful strategies of care for bereaved parents that could extend and improve care universally.

Behaviour and development of stunted and nonstunted Jamaican children.

In order to examine the mechanism whereby stunted children have poor developmental levels, we compared the behaviour of stunted (N = 78) and nonstunted (N = 26) children aged 12 to 24 months, and examined the relationship of their behaviour to their developmental levels. The effect of nutritional supplementation with or without psychosocial stimulation on the stunted children's behaviour was also examined. The children were observed at home during 4 days over a period of 6 months. The stunted children showed significantly more apathy, and less enthusiasm and variety in exploring, were less happy and more fussy. Caretakers' vocalisations to them were less warm or instructive. Stunted children's activity level, exploratory and happy behaviours were predictive of change in developmental levels measured on the Griffiths Scales, from enrolment to 12 and 24 months later. Supplementation predicted mental age at 12 and 24 months after enrolment, however, it had no significant effect on behaviour.

Feeding-based arousal effects on visual recognition memory in early infancy.

Arousal effects on a 1-trial visual recognition paired-comparison task were studied at newborn, 1-month, and 4-month test ages. Infants were tested before and after feeding, with arousal assumed to be lower after feeding. Newborns and 1-month-olds shifted from a familiarity preference before feeding to a novelty preference after feeding. A control group tested only after feeding confirmed that this shift was not due to increased stimulus exposure from the prefeeding test. By 4 months, infants showed novelty preferences independent of feeding. This age by arousal interaction for recognition memory extends previous knowledge by including endogenous arousal with age, stimulus, and length of exposure as contributors to familiarity-novelty preferences. It also extends and provides converging evidence for arousal effects on visual attention in early infancy found previously with preferential looking. A shift from subcortical to cortical dominance is supported.