Theory-based implementation of an enhanced recovery protocol for cranial surgery.

OBJECTIVE: There is growing evidence for the use of enhanced recovery protocols (ERPs) in cranial surgery. As they become widespread, successful implementation of these complex interventions will become a challenge for neurosurgical teams owing to the need for multidisciplinary engagement. Here, the authors describe the novel use of an implementation framework (normalization process theory [NPT]) to promote the incorporation of a cranial surgery ERP into routine neuro-oncology practice. METHODS: A baseline audit was conducted to determine the degree of implementation of the ERP into practice. The Normalization MeAsure Development (NoMAD) questionnaire was circulated among 6 groups of stakeholders (neurosurgeons, anesthetists, intensivists, recovery nurses, preoperative assessment nurses, and neurosurgery ward staff) to examine barriers to implementation. Based on these findings, a theory-guided implementation intervention was delivered. A repeat audit and NoMAD questionnaire were conducted to assess the impact of the intervention on the uptake of the ERP. RESULTS: The baseline audit (n = 24) demonstrated limited delivery of the ERP elements. The NoMAD questionnaire (n = 32) identified 4 subconstructs of the NPT as barriers to implementation: communal specification, contextual integration, skill set workability, and relational integration. These guided an implementation intervention that included the following: 1) teamwork-focused training; 2) ERP promotion; and 3) procedure simplification. The reaudit (n = 21) demonstrated significant increases in the delivery of 5 protocol elements: scalp block (12.5% of patients before intervention vs 76.2% of patients after intervention, p < 0.00001), recommended analgesia (25.0% vs 100.0%, p < 0.00001) and antiemetics (12.5% vs 100.0%, p < 0.00001), trial without catheter (13.6% vs 88.9%, p < 0.00001), and mobilization on the 1st postoperative day (45.5% vs 94.4%, p < 0.00001). There was a significant reduction in the mean hospital length of stay from 6.3 ± 3.4 to 4.2 ± 1.7 days (p = 0.022). Two months after implementation, a repeat NoMAD survey demonstrated significant improvement in communal specification. CONCLUSIONS: Here, the authors have demonstrated the successful implementation of a cranial surgery ERP by using a systematic theory-based approach.

A study into the viability of Synbone® as a proxy for Sus scrofa (domesticus) ribs for use with 7.62 × 51 mm Full Metal Jacket ammunition in ballistic testing.

Forensic reconstructions and ballistic testing requires the use of consistent and repeatable simulants. Synthetic bone has been developed to be mechanically similar to human bone; however, it does not have the same viscoelastic properties. Bone acts as brittle and stiff material and fails instantly under high-energy events such as ballistic impacts. Consequently, bone simulants for use in ballistic testing should show comparable energy deposition to mammalian bones. This study aims to determine if Synbone® flat plates could be a viable proxy for Sus scrofa (domesticus) ribs in ballistic testing with 7.62 × 51 mm Full Metal Jacket ammunition. 5 mm, 6 mm and 12 mm quartered Synbone® plates were embedded into 10% ballistic gelatin and shot using 7.62 mm ammunition. The models were then analysed to compare the Synbone® to a previous Sus Scrofa (domesticus) rib study and focused on energy deposition, the number of fragments within the block, angle of deviation, onset of yaw, the temporary cavity, and the permanent wound channel. No significant difference was seen between the Sus Scrofa (domesticus) and the 5 mm Sybone®. There were significant differences observed between Sus Scrofa (domesticus) ribs and 6 mm Synbone® for the number of fragments, energy deposition and projectile tract diameter, and significant differences seen between Sus scrofa (domesticus) ribs and 12 mm Synbone® for the depth of onset of yaw, energy deposition and projectile tract diameter. This study indicates that the 5 mm Synbone® plate is a suitable proxy for Sus scrofa (domesticus) ribs for use with 7.62 × 51 mm FMJ ammunition in ballistic testing.

Accuracy and Precision of Intraocular Lens Calculations Using the New Hill-RBF Version 2.0 in Eyes With High Axial Myopia.

PURPOSE: To compare the accuracy and precision of the new Hill-RBF version 2.0 (Hill-RBF 2) formula with other formulas (Barrett Universal II, Haigis, Hoffer Q, Holladay 1, and SRK/T) in predicting residual refractive error after phacoemulsification in high axial myopic eyes. DESIGN: Retrospective case series. METHODS: 127 eyes of 127 patients with axial length (AL) ≥26 mm were included. The refractive prediction error (PE) was calculated as the difference between the postoperative refraction and the refraction predicted by each formula for the intraocular lens (IOL) power actually implanted. Standard deviation (SD) of PE, median absolute PE (MedAE), proportion of eyes within ±0.25, ±0.50, and ±1.00 diopter (D) of PE were compared. A generalized linear model was used to model the mean function and variance function of the PE (indicative of the accuracy and precision) with respect to biometric variables. RESULTS: The MedAE and SD of Hill-RBF 2 were lower than that of Hoffer Q, Holladay 1, and SRK/T (P ≤ .036) and were comparable to Barrett Universal II and Haigis (P ≥ .077). Hill-RBF 2 had more eyes within ±0.25 D of the intended refraction (76 out of 127 eyes [59.84%]) compared to other formulas (P ≤ .034) except Barrett Universal II (P = .472). AL was associated with the mean function or variance function of the PE for all formulas except Hill-RBF 2. CONCLUSIONS: In this study, the precision of Hill-RBF 2 is comparable to Barret Universal II and Haigis. Unlike the other 5 formulas, its dispersion and the accuracy of the refractive prediction is independent of the AL.

C-reactive protein: what to expect after bony hip surgery for nonambulatory children and adolescents with cerebral palsy.

Bony hip reconstruction surgery in children with severe cerebral palsy is associated with high complication rates, usually postoperative chest and urinary tract infections. C-reactive protein (CRP) level is commonly used as an indication of infection; an understanding of its normal postoperative trends is crucial to allow early identification of abnormal levels and possible infection. Our aim was to describe the trends in CRP following bony hip surgery in children who had an uneventful postoperative course, on the basis that the children for whom CRP does not follow this course are likely to have a bacterial infection. A retrospective review was performed of 155 children with CP having bony hip surgery between 2012 and 2016. The median age was 9.9 years (interquartile range: 6.6-12.7). One hundred (64.5%) patients had a Gross Motor Function Classification System rating of V. All CRP levels measured in routine postoperative care were recorded, and medical records were examined for postoperative infective complications. The CRP levels of patients with clinically proven infections were excluded in order to describe what to expect in the absence of infection. Mean CRP peaked on the third postoperative day at 81 mg/l in those who had no postoperative infection. Twenty-five (16.1%) patients had a postoperative infection; their mean CRP was higher on all postoperative days and peaked at 128 mg/l on the third postoperative day. An understanding of the normal postoperative trends in CRP allows identification of those with abnormally raised levels. Postoperative CRP is consistently higher in children with an infective complication. We recommend that the CRP should be routinely checked following bony hip surgery in children with CP, and a careful search for infection undertaken in those with a raised level.

Non-mydriatic ultrawide field scanning laser ophthalmoscopy compared with dilated fundal examination for assessment of diabetic retinopathy and diabetic macular oedema in Chinese individuals with diabetes mellitus.

AIMS: To evaluate the performance of ultrawide field scanning laser ophthalmoscopy (UWF-SLO) for assessing diabetic retinopathy (DR) and diabetic macular oedema (DME) in a Chinese population, compared with clinical examination. METHODS: This is a retrospective cohort study. A series of 322 eyes from 164 patients with DM were included. Each patient underwent both dilated fundal examination with DR and DME grading by retina specialist and non-mydriatic 200° UWF-SLO (Daytona, Optos, Dunfermline, UK). The severity of DR and DME from UWF-SLO images was further graded by ophthalmologists, according to both international clinical DR and DME disease severity scales and the standard 7-field Early Treatment Diabetic Retinopathy Study (ETDRS) scale. Any DR, DME and vision-threatening DR (VTDR) were treated as endpoints for this study. RESULTS: 23 out of 322 images (7.14%), including all four cases with proliferative DR on clinical examinations, were determined as ungradable. When the international scale was used for grading UWF-SLO images, the sensitivity of any DR, DME and VTDR was 67.7%, 67.4% and 72.6%, respectively; the specificity of any DR, DME and VTDR was 97.8%, 97.3% and 97.8%, respectively. The agreement with clinical grading in picking up any DR, DME and VTDR was substantial, with κ-values of 0.634, 0.694 and 0.707, respectively. The performance of UWF-SLO was shown to be lower when ETDRS scale was used for grading the images. CONCLUSION: The performance of non-mydriatic UWF-SLO is comparable in identifying DR with that of clinical examination in a Chinese cohort. However, whether UWF-SLO can be considered as tool for screening DR is still undetermined.

The Assessment of Burden of COPD (ABC) Scale: A Reliable and Valid Questionnaire.

The newly developed Assessment of Burden of COPD (ABC) scale is a 14-item self-administered questionnaire which measures the physical, psychological, emotional and/or social burden as experienced by patients with chronic obstructive pulmonary disease (COPD). The ABC scale is part of the ABC tool that visualises the outcomes of the questionnaire. The aim of this study was to assess the reliability and construct validity of the ABC scale. This multi-centre survey study was conducted in the practices of 19 general practitioners and 9 pulmonologists throughout the Netherlands. Next to the ABC scale, patients with COPD completed the Saint George Respiratory Questionnaire (SGRQ). Reliability analyses were performed with data from 162 cases. Cronbach's alpha was 0.91 for the total scale. Test-retest reliability, measured at a two week interval (n = 137), had an intra-class correlation coefficient of 0.92. Analyses for convergent validity were performed with data from 133 cases. Discriminant and known-groups validity was analysed with data from 162 cases. The ABC scale total score had a strong correlation with the total score of the SGRQ (r = 0.72, p < 0.001) but a weak correlation with the forced expired volume in 1 second predicted (r = -0.28, p < 0.001). Subgroups with more severe disease, defined by GOLD-stage, frequency of exacerbations, activity level and depression scored statistically significantly (p < 0.05) worse on almost all domains of the ABC scale than the less severe subgroups. The ABC scale seems a valid and reliable tool with good discriminative properties.

The interaction of protein-tyrosine phosphatase α (PTPα) and RACK1 protein enables insulin-like growth factor 1 (IGF-1)-stimulated Abl-dependent and -independent tyrosine phosphorylation of PTPα.

Protein tyrosine phosphatase α (PTPα) promotes integrin-stimulated cell migration in part through the role of Src-phosphorylated PTPα-Tyr(P)-789 in recruiting and localizing p130Cas to focal adhesions. The growth factor IGF-1 also stimulates PTPα-Tyr-789 phosphorylation to positively regulate cell movement. This is in contrast to integrin-induced PTPα phosphorylation, that induced by IGF-1 can occur in cells lacking Src family kinases (SFKs), indicating that an unknown kinase distinct from SFKs can target PTPα. We show that this IGF-1-stimulated tyrosine kinase is Abl. We found that PTPα binds to the scaffold protein RACK1 and that RACK1 coordinates the IGF-1 receptor, PTPα, and Abl in a complex to enable IGF-1-stimulated and Abl-dependent PTPα-Tyr-789 phosphorylation. In cells expressing SFKs, IGF-1-stimulated phosphorylation of PTPα is mediated by RACK1 but is Abl-independent. Furthermore, expressing the SFKs Src and Fyn in SFK-deficient cells switches IGF-1-induced PTPα phosphorylation to occur in an Abl-independent manner, suggesting that SFK activity dominantly regulates IGF-1/IGF-1 receptor signaling to PTPα. RACK1 is a molecular scaffold that integrates growth factor and integrin signaling, and our identification of PTPα as a RACK1 binding protein suggests that RACK1 may coordinate PTPα-Tyr-789 phosphorylation in these signaling networks to promote cell migration.

Is sequestrectomy a viable alternative to microdiscectomy? A systematic review of the literature.

BACKGROUND: Traditionally, lumbar discectomy involves removal of the free disc fragment followed by aggressive or conservative excision of the intervertebral disc. In selected patients, however, it is possible to remove only the free fragment or sequester without clearing the intervertebral disc space. However, there is some controversy about whether that approach is sufficient to prevent recurrent symptoms and to provide adequate pain relief. QUESTIONS/PURPOSES: This systematic review was designed to pose two questions: (1) Does performing a sequestrectomy only without conventional microdiscectomy lead to an increased reherniation rate; and (2) is there a difference in the patient-reported levels of radicular pain? METHODS: Systematic MEDLINE and EMBASE searches were carried out to identify all articles published in peer-reviewed journals reporting the outcomes of interest for conventional microdiscectomy versus sequestrectomy for lumbar disc herniation from L2 to the sacrum (Level III evidence and above); hand-searching of bibliographies was also performed. A minimum of Level II evidence was required with a followup rate of greater than 75%. Followup in all studies was from 18 to 86 months. Seven studies met the inclusion criteria for this review. The studies were analyzed for operating time, hospital stay, pre- and postoperative visual analog scale, and reherniation rate. RESULTS: Patients in both the microdiscectomy and sequestrectomy groups showed comparable improvement of visual analog scale (VAS) score for leg pain. VAS score improvement ranged from 5.6 to 6.5 points in the microdiscectomy groups and 5.5 to 6.6 in the sequestrectomy group. The reherniation rate in the microdiscectomy group ranged from 2.3% to 11.8% and in the sequestrectomy groups from 2% to 12.5%. CONCLUSIONS: This review of the available literature suggests that, compared with conventional microdiscectomy, microsurgical lumbar sequestrectomy can achieve comparable reherniation rates and reduction in radicular pain when a small breach in the posterior fibrous ring is found intraoperatively.

Protein adsorption and cell attachment to patterned surfaces.

To better understand the events involved in the generation of defined tissue architectures on biomaterials, we have examined the mechanism of attachment of human bone-derived cells (HBDC) to surfaces with patterned surface chemistry in vitro. Photolithography was used to generate alternating domains of N-(2-aminoethyl)-3-aminopropyl-trimethoxysilane (EDS) and dimethyldichlorosilane (DMS). At 90 min after seeding, HBDC were localized preferentially to the EDS regions of the pattern. Using sera specifically depleted of adhesive glycoproteins, this spatial organization was found to be mediated by adsorption of vitronectin (Vn) from serum onto the EDS domains. In contrast, fibronectin (Fn) was unable to adsorb in the face of competition from other serum components. These results were confirmed by immunostaining, which also revealed that both Vn and Fn were able to adsorb to EDS and DMS regions when coated from pure solution, i.e., in the absence of competition. In this situation, each protein was able to mediate cell adhesion across a range of surface densities. Cell spreading was constrained on the EDS domains, as indicated by cell morphology and the lack of integrin receptor clustering and focal adhesion formation. This spatial constraint may have implications for the subsequent expression of differentiated function.

Engineering bone regeneration with bioabsorbable scaffolds with novel microarchitecture.

Critical-sized defects (CSDs) were introduced into rat calvaria to test the hypothesis that absorption of surrounding blood, marrow, and fluid from the osseous wound into a bioabsorbable polymer matrix with unique microarchitecture can induce bone formation via hematoma stabilization. Scaffolds with 90% porosity, specific surface areas of approximately 10 m2/g, and median pore sizes of 16 and 32 microm, respectively, were fabricated using an emulsion freeze-drying process. Contact radiography and radiomorphometry revealed the size of the initial defects (50 mm2) were reduced to 27 +/- 11 mm2 and 34 +/- 17 mm2 for CSDs treated with poly(D,L-lactide-co-glycolide). Histology and histomorphometry revealed scaffolds filled with significantly more de novo bone than negative controls (p < 0. 007), more osteoid than both the negative and autograft controls (p < 0.002), and small masses of mineralized tissue (< 15 mm in diameter) observed within the scaffolds. Based on these findings, we propose a change in the current paradigm regarding the microarchitecture of scaffolds for in vivo bone regeneration to include mechanisms based on hematoma stabilization.

Surfaces designed to control the projected area and shape of individual cells.

Materials with spatially resolved surface chemistry were designed to isolate individual mammalian cells to determine the influence of projected area on specific cell functions (e.g., proliferation, cytoskeletal organization). Surfaces were fabricated using a photolithographic process resulting in islands of cell binding N-(2-aminoethyl)-3-aminopropyl-trimethoxysilane (EDS) separated by a nonadhesive interpenetrating polymer network [poly (acrylamide-co-ethylene glycol); P (AAm-co-EG)]. The surfaces contained over 3800 adhesive islands/cm2, allowing for isolation of single cells with projected areas ranging from 100 microns 2 to 10,000 microns 2. These surfaces provide a useful tool for researching how cell morphology and mechanical forces affect cell function.

The reduction half cell in biomaterials corrosion: oxygen diffusion profiles near and cell response to polarized titanium surfaces.

Mechanically assisted corrosion processes can greatly increase the oxidation currents generated in passivating alloy systems like Co-Cr and titanium due to oxide film disruption. When oxide films are abraded, repassivation and ionic dissolution both occur at rates that are orders of magnitude higher than undisrupted surfaces. The excess electrons generated by these anodic processes must be consumed in corresponding reduction reactions that include the reduction of oxygen. If large enough, these reduction reactions may locally deplete the concentration of solution-dissolved oxygen and, in turn, affect cell behavior in the vicinity of the implant surface. To date, this hypothesis has not been tested. In the present study, a scanning electrochemical microscope was used to measure oxygen concentration profiles in vitro near a planar titanium electrode polarized to different voltages representative of those attainable by titanium undergoing mechanically assisted corrosion. The potentials investigated ranged from 0 mV to -1000 mV (AgCl). The oxygen concentration as a function of distance from the titanium surface was measured using a platinum-iridium microelectrode and an amperometric technique. Also, preliminary experiments were performed to assess the response of rat calvarial osteoblast-rich cells cultured for 2 h on titanium samples polarized to two different potentials (0 mV and -1000 mV versus AgCl). The results of this study indicate that oxygen concentrations near titanium surfaces are affected by sample potentials out to probe-sample distances as great as 500 microm. Within 2 microm of the surface, oxygen concentrations decreased by 15 to 25% for sample potentials between -100 and -500 mV. At potentials more negative than -600 mV, the oxygen concentration dropped rapidly to near zero by -900 mV. The cell experiments showed a statistically significant difference in the amount of cell spreading, as measured by projected cell area, between the two groups (p < 0.03), with the cells cultured at -1000 mV undergoing much less spreading. This implies that -1000 mV inhibits normal cell behavior at the titanium surface and that this is most likely due, at least in part, to a diminished oxygen supply.

The detachment strength and morphology of bone cells contacting materials modified with a peptide sequence found within bone sialoprotein.

Adhesion, spreading, and focal contact formation of primary bone-derived cells on quartz surfaces grafted with a 15 amino acid peptide that contained a -RGD-(-Arg-Gly-Asp-) sequence unique to bone sialoprotein was investigated. The peptide surfaces were fabricated by using a heterbifunctional crosslinker, sulfosuccinimidyal 4-(N-maleimidomethyl)cyclohexane-1-carboxylate, to link the peptide to amine functionalized quartz surfaces. Contact angle measurements, spectroscopic ellipsometry, and X-ray photoelectron spectroscopy were used to confirm the chemistry and thickness of the overlayers. A radial flow apparatus was used to characterize cell detachment from peptide-grafted surfaces. After 20 min of cell incubation, the strength of cell adhesion was significantly (p < 0.05) higher on the -RGD- compared to -RGE- (control) surfaces. Furthermore, the mean area of cells contacting the -RGD- was significantly (p < 0.05) higher than -RGE- surfaces. Vinculin staining showed formation of small focal contact patches on the periphery of bone cells incubated for 2 h on the -RGD- surfaces; however, few or no focal contacts were formed by cells seeded on the -RGE-grafted surfaces. The methods of peptide immobilization utilized in this study can be applied to implants, biosensors, and diagnostic devices that require specificity in cell adhesion.

The role of vitronectin in the attachment and spatial distribution of bone-derived cells on materials with patterned surface chemistry.

In recent years a central objective of tissue engineering has been understanding the interaction of cells with biomaterial surfaces. In this study we examined the protein adsorption events necessary to control the attachment and the subsequent spatial distribution of bone-derived cells exposed to chemically modified surfaces. Silane chemistry and photolithography techniques were used to create substrates with alternating regions of an aminosilane, N-(2-aminoethyl)-3-aminopropyl-trimethoxysilane (EDS), along side an alkylsilane, dimethyldichlorosilane (DMS), on quartz surfaces. Sera depleted of fibronectin (Fn), vitronectin (Vn), or both were used to determine if these proteins were necessary for the initial attachment and spatial distribution of bone-derived cells exposed to modified surfaces in vitro. The kinetics and mechanisms of the spatial distribution of cells were examined using light microscopy and digital image acquisition and subsequently were analyzed. Compared to complete serum, the use of serum depleted of fibronectin with vitronectin included had minimal effect on the cell attachment, spreading, and spatial distribution on the EDS regions of the surface. However, the use of serum depleted of vitronectin with or without fibronectin included resulted in greatly reduced cell attachment and spreading. Thus the presence of vitronectin was required for the attachment, spreading, and spatial distribution of bone-derived cells exposed to EDS/DMS-patterned surfaces.

A probabilistic approach to measure the strength of bone cell adhesion to chemically modified surfaces.

Patterned surfaces with alternating regions of amino silanes [N-(2-aminoethyl)-3-aminopropyl-trimethoxysilane (EDS)] and alkyl silanes [dimethyldichlorosilane (DMS)] have been used to alter the kinetics of spatial distribution of cells in vitro. In particular, we have previously observed the preferential spatial distribution of bone cells on the EDS regions of EDS/ DMS patterned surfaces (10). In this study, we examined whether the mechanism of spatial distribution of cells on the EDS regions was adhesion mediated. Homogeneous layers of EDS and DMS were immobilized on quartz substrates and characterized by contact angle. X-ray photoelectron spectroscopy, and spectroscopic ellipsometry. The strength of bone cell attachment to the modified substrates was examined using a radial flow apparatus, within either 20 min or 2 hr of cell incubation in the presence of serum. A Weibull distribution was chosen to characterize the strength of cell-substratum adhesion. Within 20 min of cell exposure, the strength of adhesion was significantly larger on EDS and clean surfaces, compared with DMS surfaces (p < 0.001). Within 2 hr of cell incubation, there was no statistical difference between the strength of cell adhesion to EDS, DMS, and clean surfaces. The results of this study suggest that the surface chemistry mediates adhesion-based spatial cell arrangement through a layer of adsorbed serum proteins.

Spinal instrumentation for Duchenne's muscular dystrophy: experience of hypotensive anaesthesia to minimise blood loss.

Nineteen patients with Duchenne's muscular dystrophy underwent segmental spinal instrumentation and posterior fusion between 1989 and 1994. The indication for surgery was loss of the ability to walk and development of scoliosis with sitting discomfort. Preoperative assessment included evaluation of pulmonary function. Average age at operation was 12.5 years. Instrumentation and fusion extended from upper thoracic levels to L-5 or the sacrum. A Hartshill rectangle was used in all cases, with banked allograft bone. Severe intraoperative blood loss was avoided by use of hypotensive anaesthesia. Peroperatively, systolic blood pressure was maintained between 75 and 85 mm Hg. Average blood loss was 1,246 ml (range, 400-3,100) or 30% of estimated total blood volume. Average transfusion requirements were 3 units of packed cells. Postoperative analgesia was provided by infusion via an epidural catheter. There were no postoperative wound or chest infections. Three patients required catheterisation for urinary retention. Postoperatively patients were fitted with a Neofract jacket to allow early mobilisation and discharge. Mean postoperative length of stay was 16 days. Posterior spinal fusion by using the Hartshill rectangle provided good correction and fixation. Hypotensive anaesthesia permitted surgery to be performed rapidly in a relatively dry field and avoided the complications of severe intraoperative blood loss and massive transfusion.

Managing chronic back pain: impact of an interdisciplinary team approach.

OBJECTIVE: To evaluate the effectiveness of a six-week outpatient program in pain management for patients with chronic back pain. DESIGN: Retrospective review. SETTING: Rehabilitation Clinical Business Unit, Essendon campus of the Royal Melbourne Hospital. SUBJECTS: 138 consecutive patients who participated in the unit's Chronic Back Pain Programme between 1991 and 1993. INTERVENTION: Multidisciplinary program that promoted pain management rather than "cure", with two six-hour group sessions per week for six weeks. OUTCOME MEASURES: Patient assessments before the program and at program completion and at three months' follow-up, with the West Haven-Yale Multidimensional Pain Inventory (WHYMPI) and a four-minute walk test. RESULTS: At program completion, the WHYMPI showed significant decreases in the amount pain interfered with life and significant increases in patient sense of control and activity level. However, severity of pain remained the same. All these effects were maintained three months later. CONCLUSIONS: A brief outpatient program was effective in improving pain management in a group of chronic back pain sufferers. This seems a useful and relatively inexpensive option in managing this problematic group of patients.

Kinetics of bone cell organization and mineralization on materials with patterned surface chemistry.

Materials with spatially resolved chemistries (i.e. patterned surfaces) have been used to guide and organize the position of mammalian cells in vitro. A common theme in guiding the spatial distribution of cells has been the use of patterned alkylsiloxanes, where one region contains an aminosilane and the other an alkylsilane. The regions of the aminosilane served as preferential sites for cell attachment and spreading, presumably dependent on the association between cell surface proteoglycans the positively charged amine. In this study, experiments were conducted with patterns of N-(2-aminoethyl)-3-aminopropyl-trimethoxysilane (EDS) and dimethyldichlorosilane (DMS) to determine the kinetics of spatial organization of bone-derived cells, and whether initial attachment and spreading affected the rate of matrix mineralization (i.e. bone formation) in extended cultures. The bone cells required the presence of serum or preadsorption of serum proteins to the patterned EDS/DMS surface to organize according to the lithographically defined surface chemistry. Time-lapse video microscopy indicated that cells were randomly distributed over the EDS/DMS surface at the time of plating, but organized on the EDS regions within 30 min. When cultures were extended for 15 and 25 days, the matrix synthesized by the cells was preferentially mineralized on the EDS chemistry. These results demonstrate the ability of surface chemistry modifications to organize cells and form mineralized tissue in vitro. The methods employed should have general value to the engineering of tissues in vitro.

Welsh water should reinstate fluoridation on Anglesey.

In 1992, Welsh Water withdrew the successful water fluoridation scheme on Anglesey. Despite evidence of the benefits of water fluoridation and the rise in number of children with tooth decay since the scheme's withdrawal, Welsh Water is still not prepared to re-establish the scheme.