“Should parental refusals of newborn screening be accepted?”

For over four decades, knowledge that symptoms of some inherited diseases can be prevented or reduced via early detection and treatment in newborns has underpinned state-funded screening programs in most developed countries. 1 Conditions for which newborn screening is now a recognized preventative public health initiative include phenylketonuria (PKU), congenital hypothyroidism (CHT), and, more recently, cystic fibrosis (CF) and sickle cell disorder (SCD). The use of tandem mass spectrometry to detect conditions such as amino-acidopathies and fatty-acid oxidation defects is also becoming increasingly prevalent. 2 The early identification of children who are at risk for these conditions can have very positive implications. To take the most significant example, a child born with mutations that would otherwise lead to symptoms of PKU will have a vastly different kind of life if the condition is detected in early infancy rather than later. The introduction of a modified diet at this time, although cumbersome, will prevent the onset of severe mental impairment, allowing the child to lead a virtually normal life. 3 Although clinical indications are sometimes more contentious when justifying screening for other conditions, by and large newborn screening is clinically valid and carries only minimal risk. However, it is sometimes declined by parents, presenting healthcare professionals with an ethical, legal, and practical dilemma. Consider the following scenario: Emma and Tom both work as pediatricians in a large city hospital. They have recently had their third child, a daughter named Clare. During a postnatal visit to their home by a midwife, Emma indicates that she and Tom do not want Clare to have any newborn screening. Emma reports there is no family history of any of the diseases being screened for, and she feels strongly that the probability Clare will have any of the conditions is so low that it cannot justify subjecting her to an invasive test. This scenario gives rise to three issues, each addressed below. First, is Emma and Tom’s refusal of newborn screening for Clare justifiable? Second, should the law ever mandate newborn screening over parental objections? Third, howshould such refusals be managed in practice? Using the example of PKU screening, it is argued that although refusals are often difficult to defend, legal intervention is unjustified as a means of compelling parents to allow their infant to be screened. Nevertheless, the state may be justified in exercising some degree of “influence” over parental decisionmaking, via the practices of health professionals involved in newborn screening.This article was written by Dr Ainsley Newson during the time of her employment with the University of Bristol, UK (2006-2012). Self-archived in the Sydney eScholarship Repository with permission of Bristol University, Sept 2014

The behavior of osteoblast-like cells on various substrates with functional blocking of integrin-β1 and integrin-β3

This study was designed to examine the influence of integrin subunit-β1 and subunit-β3 on the behavior of primary osteoblast-like cells, cultured on calcium phosphate (CaP)-coated and non coated titanium (Ti). Osteoblast-like cells were incubated with specific monoclonal antibodies against integrin-β1 and integrin-β3 to block the integrin function. Subsequently, cells were seeded on Ti discs, either non coated or provided with a 2 μm carbonated hydroxyapatite coating using Electrostatic Spray Deposition. Results showed that on CaP coatings, cellular attachment was decreased after a pre-treatment with either anti-integrin-β1 or anti-integrin-β3 antibodies. On Ti, cell adhesion was only slightly affected after a pre-treatment with anti-integrin-β3 antibodies. Scanning electron microscopy showed that on both types of substrate, cellular morphology was not changed after a pre-treatment with either antibody. With quantitative PCR, it was shown for both substrates that mRNA expression of integrin-β1 was increased after a pre-treatment with either anti-integrin-β1 or anti-integrin-β3 antibodies. Furthermore, after a pre-treatment with either antibody, mRNA expression of integrin-β3 and ALP was decreased, on both types of substrate. In conclusion, osteoblast-like cells have the ability to compensate to great extent for the blocking strategy as applied here. Still, integrin-β1 and β3 seem to play different roles in attachment, proliferation, and differentiation of osteoblast-like cells, and responses on CaP-coated substrates differ to non coated Ti. Furthermore, the influence on ALP expression suggests involvement of both integrin subunits in signal transduction for cellular differentiation

Borderline tumours of the ovary:Common practice in the Netherlands

Objectives: Discordance between frozen section diagnosis and the definite histopathological diagnosis and the fact that the frozen section result is not always unambiguous, may contribute to differences in clinical practice regarding perioperative treatment and follow-up of borderline ovarian tumours (BOTs) patients amongst gynaecologic oncologists, which may lead to over- and undertreatment. The aim of the study was to map the Dutch gynaecologists' preferred treatment and follow-up strategy in case of BOTs. Methods: A questionnaire was sent to all Dutch gynaecologists involved in ovarian surgery with perioperative frozen section analysis, and the outcomes were assessed using descriptive statistics. Results: Nearly half of the respondents (41.0%) would not perform a staging procedure in case of a BOT. In case of an ambiguous frozen section diagnosis, tending towards invasive carcinoma, a considerable number (sBOT 56.4%; mBOT 30.8%) would perform a lymph node sampling as part of the staging procedure. A relaparotomy/relaparoscopy, to perform a lymph node sampling in case of a serous or mucinous carcinoma after a BOT frozen section diagnosis, would be performed by 97.4% and 48.7% of the respondents, respectively. Conclusions: A considerable number of gynaecologists would perform a staging procedure that is recommended for ovarian cancer in case of an ambiguous BOT frozen section diagnosis, especially for serous tumours. In addition, nearly all gynaecologists would perform a second procedure including a lymph node sampling in case of a serous invasive carcinoma after a BOT frozen section diagnosis, which applies to half of the gynaecologists in case of a mucinous carcinoma. Keywords: Borderline tumours of the ovary, Staging procedure, Frozen section analysis, Questionnaire, Gynaecologic oncologist, Semi-specialized gynaecologist

A 3D Analysis of Flight Behavior of Anopheles gambiae sensu stricto Malaria Mosquitoes in Response to Human Odor and Heat

Female mosquitoes use odor and heat as cues to navigate to a suitable landing site on their blood host. The way these cues affect flight behavior and modulate anemotactic responses, however, is poorly understood. We studied in-flight behavioral responses of females of the nocturnal malaria mosquito Anopheles gambiae sensu stricto to human odor and heat. Flight-path characteristics in a wind tunnel (flow 20 cm/s) were quantified in three dimensions. With wind as the only stimulus (control), short and close to straight upwind flights were recorded. With heat alone, flights were similarly short and direct. The presence of human odor, in contrast, caused prolonged and highly convoluted flight patterns. The combination of odor+heat resulted in longer flights with more landings on the source than to either cue alone. Flight speed was greatest (mean groundspeed 27.2 cm/s) for odor+heat. Odor alone resulted in decreased flight speed when mosquitoes arrived within 30 cm of the source whereas mosquitoes exposed to odor+heat maintained a high flight speed while flying in the odor plume, until they arrived within 15 cm of the source. Human odor evoked an increase in crosswind flights with an additive effect of heat at close range