Lighting the Path: Light Delivery Strategies to Activate Photoresponsive Biomaterials In Vivo

Photoresponsive biomaterials are experiencing a transition from in vitro models to in vivo demonstrations that point toward clinical translation. Dynamic hydrogels for cell encapsulation, light-responsive carriers for controlled drug delivery, and nanomaterials containing photosensitizers for photodynamic therapy are relevant examples. Nonetheless, the step to the clinic largely depends on their combination with technologies to bring light into the body. This review highlights the challenge of photoactivation in vivo, and presents strategies for light management that can be adopted for this purpose. The authors’ focus is on technologies that are materials-driven, particularly upconversion nanoparticles that assist in “direct path” light delivery through tissue, and optical waveguides that “clear the path” between external light source and in vivo target. The authors’ intention is to assist the photoresponsive biomaterials community transition toward medical technologies by presenting light delivery concepts that can be integrated with the photoresponsive targets. The authors also aim to stimulate further innovation in materials-based light delivery platforms by highlighting needs and opportunities for in vivo photoactivation of biomaterials.     

Ends,Means and Innovation Management

The management of innovation inevitably implies the management of uncertainty. Research and practise clearly indicate that judgements about the size and the nature of this are often inaccurate. This can result in poor performance against expectations and in some cases in complete failure. In this paper it is argued that prior analysis of the type of uncertainty can help to improve the success rate and/or reduce the time to completion. Early signs that discontinuation, or a significant change in direction, might be called for are also highlighted by this analysis.     

Parents and procedures: a randomized controlled trial

INTRODUCTION: Previous work has shown that parents prefer to be present when their children undergo common invasive procedures, although physicians are ambivalent about parental presence. PURPOSE: To determine the effect of a parent-focused intervention on the pain and performance of the procedure, anxiety of parents and clinicians, and parental satisfaction with care. POPULATION: Children younger than 3 years old undergoing venipuncture, intravenous cannulation, or uretheral catheterization. SETTING: Pediatric emergency department of Boston City Hospital. DESIGN: Randomized controlled trial with three groups; parents present and given instructions on how to help their children; parents present, but no instructions given; and parents not present. INTERVENTION: The parents were instructed to touch, talk to, and maintain eye contact during the procedure. RESULTS: A total of 431 parents was randomized to the intervention (N = 153), present (N = 147), and not present (N = 131) groups. The groups were equivalent with respect to measured sociodemographic variables and parents' previous experience in the pediatric emergency department. No differences emerged with respect to pain (3-point scale measured by parent and clinician, and analysis of cry); performance of the procedure (number of attempts, completion of procedure by first clinician, time); clinician anxiety; or parental satisfaction with care. Parents who were present were more likely to rate the pain of the children as extreme/severe (52%) in comparison to clinicians (15%, kappa .07, poor agreement) and were significantly less anxious than parents who were not present. CONCLUSION: Overall, the intervention was not effective in reducing the pain of routine procedures. Parental presence did not negatively affect performance of the procedure or increase clinician anxiety. Parents who were present were less anxious than those who were not present. CLINICAL IMPLICATION: In general, parents have indicated that they want to be present when their children undergo procedures. The results of this study challenge the traditional belief that parental presence negatively affects our ability to successfully complete procedures. We should encourage parents who want to be present to stay during procedures.     

Rapid identification of protein phosphatase 1-binding proteins by mixed peptide sequencing and data base searching. Characterization of a novel holoenzymic form of protein phosphatase 1

Microcystin-affinity chromatography was used to purify 15 protein phosphatase 1 (PP1)-binding proteins from the myofibrillar fraction of rabbit skeletal muscle. To reduce the time and amount of material required to identify these proteins, proteome analysis by mixed peptide sequencing was developed. Proteins are resolved by SDS-polyacrylamide gel electrophoresis, electroblotted to polyvinylidene fluoride membrane, and stained. Bands are sliced from the membrane, cleaved briefly with CnBr, and applied without further purification to an automated Edman sequencer. The mixed peptide sequences generated are sorted and matched against the GenBank using two new programs, FASTF and TFASTF. This technology offers a simple alternative to mass spectrometry for the subpicomolar identification of proteins in polyacrylamide gels. Using this technology, all 15 proteins recovered in PP-1C affinity chromatography were sequenced. One of the proteins, PP-1bp55, was homologous to human myosin phosphatase, MYPT2. A second, PP-1bp80, identified in the EST data bases, contained a putative PP-1C binding site and a nucleotide binding motif. Further affinity purification over ATP-Sepharose isolated PP-1bp80 in a quaternary complex with PP-1C and two other proteins, PP-1bp29 and human p20. Recombinant PP-1bp80 also bound PP-1C and suppressed its activity toward a variety of substrates, suggesting that the protein is a novel regulatory subunit of PP-1.     

Components of genetic variance and covariance for linear type traits in Jersey cattle

First available appraisals for 67,644 Jersey cows were used to estimate relative magnitudes of additive and selected sources of nonadditive genetic variance and covariance for 13 type traits scored linearly from 50 to 99 points. Covariances among four types of relatives were used to estimate components of genetic variance and covariance for each of the 13 traits. Direct additive, direct dominance, and additive maternal genetic variances and the direct-maternal additive genetic covariance were estimated using covariances among paternal half-sibs, full-sibs, daughters and dams, and maternal half-sibs. Estimates of additive genetic variance were 11 to 36% of variance within herd-appraiser subclasses with largest values for stature, strength, rump angle, rump width, and udder depth. Dominance components were two to four times the magnitude of additive components for dairy character, rump width, fore udder, rear udder height, rear udder width, and suspensory ligament but much smaller for other traits. Maternal effects and the direct-maternal additive genetic covariance appeared small for all linear type traits.     

Nonlinear discrete-time models: state-space vs. I/O representations

This paper compares state-space and input–output realizations for nonlinear discrete-time dynamic models. For linear models, these two realizations are essentially equivalent and their structures are closely related, but these statements do not hold for nonlinear models. We illustrate this point with simple, realistic examples for which only one of the two realizations exists or for which both exist but their structures are profoundly different. Overall, the main point of this paper is the importance of the choice of realization in the development of nonlinear dynamic models.     

Juvenile chronic arthritis: a cephalometric analysis of the facial skeleton

A retrospective cross-sectional cephalometric investigation was undertaken to examine the facial form of a group of Finnish children with juvenile chronic arthritis (JCA). Following digitization, the radiographs were divided into three age groups, and according to whether or not 'bird-face' deformity was present. From a total of 67 cases (39 females and 28 males) 19 per cent were judged to be 'affected'. Analyses were carried out and the groups compared using t-tests. The mandible was found to be smaller both in ramal height and body length in the affected sample, with reduction in posterior face height being only partly compensated by increase in bony apposition at the angle producing antegonial notching. There was posterior rotation of the mandible with a reduction in angles S-N-B and S-N-Pog, and an increase in the gonial angle, the angle between the mandibular plane and S-N, maxillary, and occlusal planes. The changes in the maxilla were less marked. Although S-N-A was reduced in all three age groups, it was not significantly so. Maxillary length (ANS-PNS) was significantly smaller in the two younger age groups. In the vertical plane maxillary dimensions were reduced in the two younger age groups. A highly significant increase in the occlusal to maxillary planes angle was observed in all groups. There was, however, no difference in S-N to maxillary planes angle, indicating a more steeply inclined occlusal plane due to subnormally erupted maxillary molars. Although the inter-incisal angle was reduced there was no significant difference in the incisor inclinations in relation to the jaws and despite the posterior rotation of the mandible there was no significant increase in size of overjet or in the frequency of anterior open bite.     

PVC as a food packaging material

Manufacture of polyvinyl chloride (PVC) in western Europe for all applications is now almost 4 m tonnes and the UK accounts for about 400 kt of this.The aim of this paper is to illustrate the relative importance of PVC as a packaging material where, in the UK for example, for food packaging it accounts for almost 40 kt (10%) of the PVC used.The different types of PVC packaging material—bottles, foil, cling film and cap sealing—and their method of manufacture are described, together with the range of food packaging applications in which they are used. The physical properties of PVC are described and, additionally, its cost and competitiveness with other materials are compared. The chemical nature of PVC compositions arising from the addition of heat stabilisers and plasticisers to achieve the desired properties is also described, with particular reference to heat stability.With the VCM toxicity issue now behind us, and PVC polymer with a maximum level of 1 ppm vinyl chloride monomer (VCM) being supplied for food packaging, PVC must be the most stringently controlled and thoroughly researched material for food packaging. Recent developments in polymerisation technology and polymer manufacture, which have enabled this level to be achieved, are briefly described.The current situation on the global migration issue, on which attention is currently focused, not only for plasticised PVC, but also other packaging materials as well, is briefly reviewed.     

Heritabilities for Lactation Average of Somatic Cell Counts in First,Second, and Third or Later Parities

Heritabilities were estimated for lactation average log, base 2, somatic cell count from cows with four or more tests in each lactation. Estimates were for first, second, and third or later parities (defined by age at calving) individually and for mixed parities. Estimates were from sire components of variance with numbers of sires and daughters of 406 and 22,140; 337 and 8,659; 311 and 6,122; and 310 and 10,217 for mixed, first, second, and third or later parities, respectively.Both sire and error components of variance increased with parity. Heritabilities were .18, .09, .10, and .29, for mixed, first, second, and third or later parities.