A systematic review of early life factors which adversely affect subsequent lung function.

It has been known for many years that multiple early life factors can adversely affect lung function and future respiratory health. This is the first systematic review to attempt to analyse all these factors simultaneously. We adhered to strict a priori criteria for inclusion and exclusion of studies. The initial search yielded 29,351 citations of which 208 articles were reviewed in full and 25 were included in the review. This included 6 birth cohorts and 19 longitudinal population studies. The 25 studies reported the effect of 74 childhood factors (on their own or in combinations with other factors) on subsequent lung function reported as percent predicted forced expiration in one second (FEV1). The childhood factors that were associated with a significant reduction in future FEV1 could be grouped as: early infection, bronchial hyper-reactivity (BHR) / airway lability, a diagnosis of asthma, wheeze, family history of atopy or asthma, respiratory symptoms and prematurity / low birth weight. A complete mathematical model will only be possible if the raw data from all previous studies is made available. This highlights the need for increased cooperation between researchers and the need for international consensus about the outcome measures for future longitudinal studies.

Obstetric and perinatal outcomes in pregnancies complicated by Type 1 and Type 2 diabetes: influences of glycaemic control, obesity and social disadvantage.

AIMS: To compare obstetric and perinatal outcomes in women with Type 1 and Type 2 diabetes and relate these to maternal risk factors. METHODS: Prospective cohort study of 682 consecutive diabetic pregnancies in East Anglia during 2006-2009. Relationships between congenital malformation, perinatal mortality and perinatal morbidity (large for gestational age, preterm delivery, neonatal care) with maternal age, parity, ethnicity, glycaemic control, obesity and social disadvantage were examined using bivariable and multivariate models. RESULTS: There were 408 (59.8%) Type 1 and 274 (40.2%) Type 2 diabetes pregnancies. Women with Type 2 diabetes were older (P < 0.001), heavier (P < 0.0001), more frequently multiparous (P < 0.001), more ethnically diverse (p < 0.0001) and more socially disadvantaged (P = 0.0004). Although women with Type 2 diabetes had shorter duration of diabetes (P < 0.0001) and better pre-conception glycaemic control [HbA(1c) 52 mmol/mol (6.9%) Type 2 diabetes vs. 63 mmol/l (7.9%) Type 1 diabetes; p < 0.0001), rates of congenital malformation and perinatal mortality were comparable. Women with Type 2 diabetes had fewer large-for-gestational-age infants (37.6 vs. 52.9%, P < 0.0008), fewer preterm deliveries (17.5 vs. 37.1%, P < 0.0001) and their offspring had fewer neonatal care admissions (29.8 vs. 43.2%, P = 0.001). Third trimester HbA(1c) (OR 1.35, 95% CI 1.09-1.67, P = 0.006) and social disadvantage (OR 0.80, 95% CI 0.67-0.98; P = 0.03) were risk factors for large for gestational age. CONCLUSIONS: Despite increased age, parity, obesity and social disadvantage, women with Type 2 diabetes had better glycaemic control, fewer large-for-gestational-age infants, fewer preterm deliveries and fewer neonatal care admissions. Better tools are needed to improve glycaemic control and reduce the rates of large for gestational age, particularly in Type 1 diabetes.

Personal experiences of women with diabetes who do not attend pre-pregnancy care.

AIMS: To explore the views of women who did not attend pre-pregnancy care (PPC), in particular their accounts of contraception, previous pregnancies and the influence of healthcare advice. METHODS: We conducted semi-structured interviews with 29 pregnant women (21 with Type 1 diabetes, eight with Type 2 diabetes) at three UK specialist diabetes antenatal clinics. Interviews explored women's journeys to becoming pregnant, including use of contraception, their views regarding diabetes and pregnancy and the factors which encouraged and discouraged them from attending PPC. RESULTS: All women had some understanding of the issues concerning diabetes during pregnancy, predominantly regarding the benefits of PPC (90%) and optimal glycaemic control (80%) and risks of malformation (48%) and macrosomia (35%). Most were not regularly using contraception (70%), having stopped deliberately (45%), become unintentionally less rigorous (28%) or experienced side effects/contraindications (14%). Knowledge concerning the risks of pregnancy (90%) and past pre-conception counselling (38%) did not encourage women to attend PPC, and neither did personal experience of miscarriage, malformation or stillbirth in women with previous poor pregnancy outcome (41%). Barriers included conceiving faster than anticipated (45%), fertility concerns (31%), negative experiences with health professionals (21%), desire for a 'normal' pregnancy (17%) and the logistics of attending (10%). CONCLUSIONS: More integrated diabetes and reproductive health/contraceptive advice, increased awareness of the potentially short time between stopping contraception and conception and more intensive support between pregnancies are required, particularly for women with previously poor outcomes. Research is also needed into how communication between health professionals and women with diabetes can be improved.

Improving the colonization and functions of Wharton's Jelly-derived mesenchymal stem cells by a synergetic combination of porous polyurethane scaffold with an albumin-derived hydrogel.

The development of neo-tissues assisted by artificial scaffolds is continually progressing, but the reproduction of the extracellular environment surrounding cells is quite complex. While synthetic scaffolds can support cell growth, they lack biochemical cues that can prompt cell proliferation or differentiation. In this study, Wharton's Jelly-derived mesenchymal stem cells are seeded on a polyurethane (PU) scaffold combined with a hydrogel based on bovine serum albumin (BSA). BSA hydrogel is obtained through thermal treatment. While such treatment leads to partial unfolding of the protein, we show that the extent of denaturation is small enough to maintain its bioactivity, such as protein binding. Therefore, BSA provides a suitable playground for cells inside the scaffold, allowing higher spreading, proliferation and matrix secretions. Furthermore, the poor mechanical properties of the hydrogel are compensated for by the porous PU scaffold, whose architecture is well controlled. We show that even though PU by itself can allow cell adhesion and protein secretion, cell proliferation is 3.5 times higher in the PU + BSA scaffolds as compared to pure PU after 21 d, along with the non-collagenous protein secretions (389 versus 134 µmmg -1). Conversely, the secretion of sulphated glycosaminoglycans is 12.3-fold higher in the scaffold made solely of PU. Thereby, we propose a simple approach to generating a hybrid material composed of a combination of PU and BSA hydrogel as a promising scaffold for tissue regeneration.

The value of ultrasound with ultrasound-guided fine-needle aspiration biopsy compared to computed tomography in the detection of regional metastases in the clinically negative neck.

PURPOSE: Head and neck oncologists have not reached consensus regarding the role of contemporary imaging techniques in the evaluation of the clinically negative neck in patients with head and neck squamous cell carcinoma (HNSCC). The purpose of the present study was to compare the accuracy of ultrasound with guided fine-needle aspiration biopsy (UGFNAB) and computed tomography (CT) in detecting lymph node metastasis in the clinically negative neck. METHODS AND MATERIALS: Sixty-four neck sides of patients with HNSCC were examined preoperatively by ultrasound/UGFNAB and CT at one of five participating tertiary care medical centers. The findings were correlated with the results of histopathologic examination of the neck specimen. RESULTS: Ultrasound with guided fine-needle aspiration biopsy was characterized by a sensitivity of 48%, specificity of 100%, and overall accuracy of 79%. Three cases had nondiagnostic aspirations using UGFNAB and were excluded. CT demonstrated a sensitivity of 54%, specificity of 92%, and overall accuracy of 77%. UGFNAB detected two additional metastases not visualized on CT, whereas CT detected no metastases not seen on UGFNAB. The results of UGFNAB were similar between the participating centers. CONCLUSIONS: Approximately one half of the clinically occult nodal metastases in our patient group were identified by both CT and UGFNAB. Overall, UGFNAB and CT demonstrated comparable accuracy. The sensitivity of CT was slightly better than UGFNAB, but the latter remained characterized by a superior specificity. The results of CT and UGFNAB did not appear to be supplementary. The choice of imaging modality for staging of the clinically negative neck depends on tumor site, T-stage, and experience and preference of the head and neck oncologist. If CT is required for staging of the primary tumor, additional staging of the neck by UGFNAB does not provide significant additional value.

Pediatric residency as preparation for primary care practice.

OBJECTIVES: To assess the effectiveness of pediatric residency training as preparation for primary care and make recommendations for improving residency training. METHOD: Two surveys were sent to graduate of the pediatric residency at the University of Colorado from 1984 to 1991. The first survey requested information about practice patterns and ratings of preparedness in 45 areas important for primary care. The second survey requested ratings of importance for increasing training time in 25 areas judged as inadequate in the first survey. RESULTS: Of 147 surveys mailed, 103 graduates responded and rated themselves as less than adequately trained in 25 of 45 areas selected for relevance to primary care. Graduates of the primary care track rated themselves as significantly better trained than graduates of nonprimary care tracks in 10 of 45 areas; nonprimary care graduates had higher ratings in 2 of 45 areas. The second survey (completed by 70 of the 103 initial responders) indicated that the top 5 areas needing increased time in residency training were, in descending order, orthopedics, developmental and behavioral problems, learning disability, attention-deficit hyperactivity disorder, and school difficulty. Graduates of the primary care track rated themselves as adequately trained in developmental and behavioral problems and attention-deficit hyperactivity disorder, but they and nonprimary care graduates felt inadequately prepared in the other 3 areas. CONCLUSION: Implications of these results change with different content areas, suggesting the need to improve training for all residents in some areas and extending to all residents some of the curriculum already implemented in the primary care track.

Protein-calixarene interactions: complexation of Bovine Serum Albumin by sulfonatocalix[n]arenes.

The complexation of Bovine Serum Albumin with sulfonatocalix[n]arenes has been demonstrated by means of electrospray mass spectrometry, dynamic light scattering and atomic force microscopy; with sulfonatocalix[4]arene one strong and two weaker binding sites are detected; the effects on the structure of thin films formed by surface deposition of BSA show that the sulfonatocalix[n]arenes act to reticulate the films and produce essentially planar systems.

p-Sulfonatocalix[6]arene is an effective coacervator of poly(allylamine hydrochloride).

p-Sulfonatocalix[6]arene is shown to form insoluble complexes with poly(allylamine hydrochloride) when the charge balance between the negative calixarene sulfonate groups matches the positive charge carried by the polyelectrolyte, this makes this glycosylaminoglycan analog an interesting candidate for controlled release systems in the case of proteins encapsulated in mesoscopic complexes with polyelectrolytes.

A microprocessor-based acoustic hearing aid for the profoundly impaired listener.

We have found that the larynx-frequency pattern of speech presented as a sinusoid can be of greater communicative value to profoundly hearing-impaired people than the complete acoustic signal. The presence of higher harmonics can give poorer labelling of isolated intonation contrasts and often minimal gain in segmental spectrally-based distinctions. These observations have led to the development of a practical, body-worn, pattern-processing hearing aid that uses a microprocessor to sense the (analogue-processed) speech fundamental frequency, transform it into an appropriate amplitude and frequency region, and generate digitally the required output sinusoid. Our findings have important implications for the design of other signal-processing hearing aids in demonstrating that a simplification of speech can lead to enhanced speech receptive abilities in persons with impaired hearing.

p53 immunostaining of surgical margins as a predictor of local recurrence in squamous cell carcinoma of the oral cavity and oropharynx.

Local and regional recurrence is the principal reason for treatment failure in squamous cell carcinoma (SCC) of the head and neck. The conventional method of evaluating surgical margins for cellular atypia does not always predict risk of local recurrence accurately. Immunostaining of surgical margins for tumor markers may provide a more precise evaluation of risk of local recurrence. Paraffin-embedded tissue blocks of surgical margins from 24 patients with oral cavity and oropharyngeal squamous cell carcinoma were immunostained for p53 protein. Fifty-eight percent of the patients had at least one margin stain positive for p53, including eight of ten patients whose SCC recurred locally. The sample odds ratio test predicted a 5.333 times higher chance of local recurrence with at least one p53 positive surgical margin. The implications of these results for patient management and further investigations will be discussed.

Polyphosphates as inorganic polyelectrolytes interacting with oppositely charged ions, polymers and deposited on surfaces: fundamentals and applications.

Polyphosphates are important but neglected polyelectrolytes that play a major role in biology and in surface science for the stabilization of colloids against flocculation and for the preservation of food. They are also known as "Calgon" ® and intensively used as additives in washing powders. This review aims to review recent developments in which linear polyphosphates are used for the design of new functional coatings using sol-gel processes and layer-by-layer deposition methods. All these methods rely on the high charge density of polyphosphates as inorganic polyelectrolytes, therefore the structure and properties of these molecules are also reviewed. New perspectives will also been given for the design of stimuli responsive coatings at the tiny frontier between biology and materials science.

Peculiar reduction of graphene oxide into graphene after diffusion in exponentially growing polyelectrolyte multilayers.

In the present work, in situ reduction of graphene oxide (GO) into graphene was preformed, after diffusion in exponentially growing polyelectrolyte multilayers, using sodium citrate as the reducing agent. First, the graphene oxide was obtained by treating a commercial grade of Expanded Graphite (EG). Based on XRD and Raman spectroscopy results, a complete exfoliation of graphene nanopellets down to one layer was achieved during the oxidation process. Secondly, the diffusion of GO was carried out in an exponentially growing polyelectrolyte multilayer film made from poly(diallyldimethylammonium chloride) as the polycation and from poly(acrylic acid) as the polyanion. Electrical conductivity of the GO based films was measured during the reduction process as a function of time. The conductivity reached values of the order of 10(-4) S cm(-1), whereas the pristine polyelectrolyte multilayer was highly insulating (∼10(-8) S cm(-1)). The conductivity also reached a maximal value after about 24 h of reduction and decreased for longer reduction duration. Some tentative explanations for this peculiar finding will be given.

Layer by layer self-assembled polyelectrolyte multilayers with embedded phospholipid vesicles obtained by spraying: integrity of the vesicles.

In a previous paper (Michel, M.; Vautier, D.; Voegel, J.-C.; Schaaf, P.; Ball, V. Langmuir 2004, 20, 4835), we showed that phospholipid vesicles can be incorporated into poly(glutamic-acid)/poly(allylamine) (PGA/PAH) multilayered polyelectrolyte films built by the alternated dipping of a surface in polyanion and polycation solutions. AFM imaging, quartz crystal microbalance, and ellipsometry suggested that the vesicles remain intact when adhering on the surface. In the present paper, we show that such films can also be realized by spraying both the polyelectrolyte solutions and the vesicles onto the surface. Using such vesicles filled with ferrocyanide ions, we prove by cyclic voltammetry that the sprayed vesicles remain intact when embedded in the multilayers. We show that multilayers containing two distinct layers of intact vesicles separated by several polyanion/polycation bilayers can also be constructed. Polyelectrolyte multilayers containing layers of phospholipid vesicles could act as reservoirs for drug or other biologically active molecules in controlled release bioactive coatings.

Multivalent ion/polyelectrolyte exchange processes in exponentially growing multilayers.

We show, in this paper that multivalent ferrocyanide anions can penetrate into exponentially growing (PGA/PAH)n multilayer films whatever the nature of the last deposited layer. These ions are not able to diffuse out of the film when it is brought in contact with a pure buffer solution. However, the contact of this film with a poly(allylamine) (PAH) or a poly(L-glutamic acid) (PGA) solution leads to the release of ferrocyanide ions from the multilayer. It is shown that the release of ferrocyanide anions, when the film is in contact with a PGA solution, is due to the diffusion of the PGA chains into the film so that an exchange between ferrocyanide ions and PGA chains takes place inside the film. On the other hand, PAH chains do not diffuse into PGA/PAH multilayers. When the film is then brought in contact with a PAH solution, the PAH chains from the solution are expected to strongly interact with the ferrocyanide ions and thus induce a diffusion mechanism of the multivalent anions out of the film, the film/solution interface playing the role of a sink for these ions. This work thus shows that interactions between multivalent ions and exponentially growing films are much more complex than expected at first sight and that polyelectrolyte multilayers must be seen as dynamic entities in which diffusion and exchange processes can take place.

The pregnancies of women with Type 2 diabetes: poor outcomes but opportunities for improvement.

AIM: To compare the outcomes of Type 1 and Type 2 diabetic pregnancies and identify risk factors for poor outcome of Type 2 pregnancies METHODS: The data from all (389 Type 1 and 146 Type 2) pre-gestational diabetic pregnancies from 10 UK hospitals were collected prospectively. RESULTS: The Type 2 mothers were less likely to have documented pre-pregnancy counselling (28.7 vs. 40.5%; P<0.05) or be taking folic acid at conception (21.9 vs. 36.4%; P<0.001) than Type 1 mothers. The percentage of pregnancies having a serious adverse outcome was higher in Type 2 patients (16.4 vs. 6.4%; P=0.002). Congenital abnormalities (12.3% in Type 2 vs. 4.4% in Type 1; P=0.002) accounted for most of this difference. The HbA1c of the Type 2 patients was similar to that of the Type 1 with mean first trimester HbA1c of 7.22 and 7.35%, respectively (P=0.5). Treatment with oral hypoglycaemic agents [odds ratio (OR), 1.8; 95% confidence interval (CI), 1.0-3.3; P=0.04], body mass index (OR, 1.09; 95% CI, 1.01-1.18; P=0.02) and folic acid supplementation (OR, 0.3; 95% CI, 0.09-1.0; P=0.04) were all independently associated with congenital malformation. CONCLUSION: Type 2 diabetic pregnancies are characterized by poor pre-pregnancy planning, inadequate folic acid supplementation and treatment with oral hypoglycaemic agents, all of which may contribute to the serious adverse outcomes affecting one in six Type 2 diabetic pregnancies. These remediable aspects of the pre-pregnancy care of women with Type 2 diabetes provide opportunities for improving the outcome towards that of women with Type 1 diabetes.

Mechanically responsive films of variable hydrophobicity made of polyelectrolyte multilayers.

Mechanically responsive surfaces that allow to switch reversibly from a hydrophobic to a hydrophilic substrate are reported. The surfaces are constituted of polyelectrolyte multilayers deposited on modified charged silicone sheets. n bilayers of poly(allylamine)-Nafion (PAH-Naf) and m bilayers of poly(allylamine)-poly(acrylic acid) (PAH-PAA) composed the multilayers. A (PAH-Naf)(n) film possesses a water contact angle of around 105 degrees, whereas the contact angle of a (PAH-Naf)(4)-(PAH-PAA)(m) multilayer is around 50 degrees. When such a film with m < 5 and terminated by PAA is stretched out, its water contact angle increases up to around 100 degrees. Successive elongation/retraction cycles allow the water contact angle to alternate reversibly between 100 and 57 degrees indicating the reversible mechanical responsive nature of the film.

Computer-based tools for assessment and remediation of speech.

The electrolaryngograph (ELG), first conceived in the 1970s, has been used extensively as a tool in both research and clinical practice. Recent software developments have extended its clinical utility for both quantitative assessment of voice production and as an interactive visual display for remediation and teaching. In this paper, we discuss applications of the electrolaryngograph, highlighting general principles of computer-based assessment and remediation.

Speech perception with the Vienna extra-cochlear single-channel implant: a comparison of two approaches to speech coding.

Although it is generally accepted that single-channel electrical stimulation can significantly improve a deafened patient's speech perceptual ability, there is still much controversy surrounding the choice of speech processing schemes. We have compared, in the same patients, two different approaches: (1) The speech pattern extraction technique of the EPI group, London (Fourcin et al., British Journal of Audiology, 1979,13,85-107) in which voice fundamental frequency is extracted and presented in an appropriate way, and (2) The analogue 'whole speech' approach of Hochmair and Hochmair-Desoyer (Annals of the New York Academy of Sciences, 1983, 405, 268-279) of Vienna, in which the microphone-sensed acoustic signal is frequency-equalized and amplitude-compressed before being presented to the electrode. With the 'whole-speech' coding scheme (which they used daily), all three patients showed an improvement in lipreading when they used the device. No patient was able to understand speech without lipreading. Reasonable ability to distinguish voicing contrasts and voice pitch contours was displayed. One patient was able to detect and make appropriate use of the presence of voiceless frication in certain situations. Little sensitivity to spectral features in natural speech was noted, although two patients could detect changes in the frequency of the first formant of synthesised vowels. Presentation of the fundamental frequency only generally led to improved perception of features associated with it (voicing and intonation). Only one patient consistently showed any advantage (and that not in all tests) of coding more than the fundamental alone.

The effects of two different speech-coding strategies on voice fundamental frequency control in deafened adults.

Control of voice fundamental frequency (Fx) during reading of a standard passage was assessed for four profoundly deafened adults receiving auditory feedback in one of two conditions: (i) with an extended low-frequency response amplifying aid; (ii) with the SiVo aid, which provided only Fx information. A third condition, where the subjects were unaided, was also included. For each feedback condition, quantitative analyses of laryngograph recordings were used to provide measures of Fx mode, 90% Fx range and the regularity of vocal fold vibration. In baseline unaided recordings, three subjects (S1, S2 and S4) showed some aspects of Fx control outside the normal range, while the other (S3) had appropriate Fx control. In the three subjects with impaired control, simplified Fx feedback led to better control than feedback from amplified speech. In two of these subjects, these differences were statistically significant. S3, who showed unimpaired Fx control, did not show any changes in Fx control under the different feedback conditions. Although the patterns of data were different in the individual subjects, simplified Fx feedback led to either improved or unimpaired control of Fx relative to speech feedback or to not feedback. These findings have important implications for speech-processing strategies implemented in hearing aids and cochlear implants, where the effects of different speech-coding strategies on production have been largely ignored.

Effect of text complexity on connected discourse tracking rate.

The effect of three levels of text complexity upon connected discourse tracking rates was investigated in normal listeners who tracked by lipreading alone and by lipreading with auditorily presented voice pitch. Text complexity affected connected discourse tracking under both lipreading conditions, with tracking rates decreasing as the level of text complexity increased. The improvement in tracking rate with the addition of voice pitch information was found to be invariant over changes in text complexity when expressed as a simple difference between the two tracking rates.