Acceleration management: the semiconductor industry confronts the 21st century

In the recent generations of semiconductor devices, the semiconductor industry has been accelerating towards the limits of the physical sciences. As a consequence, technology managers in that industry face seven major challenges, which will threaten progress: process, complexity, performance, power, density, productivity, and quality / reliability. We believe that confronting these challenges requires a new approach to technology management both within organizations and between organizations that form the backbone of the industry. We call this new approach Acceleration Management. Acceleration Management first requires that firms cultivate deep technical knowledge and inspire creative solutions to seemingly insoluble technical problems. The second stage of Acceleration Management requires the necessary expertise to be pooled, which often demands inter-organizational cooperation. This paper explores these managerial imperatives and analyzes how new semiconductor firms--particularly in China--have created niches in the value chain even during a tumultuous time in the industry\u27s history

Achilles and tail tendons of perlecan exon 3 null heparan sulphate deficient mice display surprising improvement in tendon tensile properties and altered collagen fibril organisation compared to C57BL/6 wild type mice

The aim of this study was to determine the role of the perlecan (Hspg2) heparan sulphate (HS) side chains on cell and matrix homeostasis in tail and Achilles tendons in 3 and 12 week old Hspg2 exon 3 null HS deficient (Hspg2Δ3 − ∕Δ3 −) and C57 BL/6 Wild Type (WT) mice. Perlecan has important cell regulatory and matrix organizational properties through HS mediated interactions with a range of growth factors and morphogens and with structural extracellular matrix glycoproteins which define tissue function and allow the resident cells to regulate tissue homeostasis. It was expected that ablation of the HS chains on perlecan would severely disrupt normal tendon organization and functional properties and it was envisaged that this study would better define the role of HS in normal tendon function and in tendon repair processes. Tail and Achilles tendons from each genotype were biomechanically tested (ultimate tensile stress (UTS), tensile modulus (TM)) and glycosaminoglycan (GAG) and collagen (hydroxyproline) compositional analyses were undertaken. Tenocytes were isolated from tail tendons from each mouse genotype and grown in monolayer culture. These cultures were undertaken in the presence of FGF-2 to assess the cell signaling properties of each genotype. Total RNA was isolated from 3–12 week old tail and Achilles tendons and qRT-PCR was undertaken to assess the expression of the following genes Vcan, Bgn, Dcn, Lum, Hspg2, Ltbp1, Ltbp2, Eln and Fbn1. Type VI collagen and perlecan were immunolocalised in tail tendon and collagen fibrils were imaged using transmission electron microscopy (TEM). FGF-2 stimulated tenocyte monolayers displayed elevated Adamts4, Mmp2, 3, 13 mRNA levels compared to WT mice. Non-stimulated tendon Col1A1, Vcan, Bgn, Dcn, Lum, Hspg2, Ltbp1, Ltbp2, Eln and Fbn1 mRNA levels showed no major differences between the two genotypes other than a decline with ageing while LTBP2 expression increased. Eln expression also declined to a greater extent in the perlecan exon 3 null mice (P < 0.05). Type VI collagen and perlecan were immunolocalised in tail tendon and collagen fibrils imaged using transmission electron microscopy (TEM). This indicated a more compact form of collagen localization in the perlecan exon 3 null mice. Collagen fibrils were also smaller by TEM, which may facilitate a more condensed fibril packing accounting for the superior UTS displayed by the perlecan exon 3 null mice. The amplified catabolic phenotype of Hspg2Δ3 − ∕Δ3 − mice may account for the age-dependent decline in GAG observed in tail tendon over 3 to 12 weeks. After Achilles tenotomy Hspg2Δ3 − ∕Δ3 − and WT mice had similar rates of recovery of UTS and TM over 12 weeks post operatively indicating that a deficiency of HS was not detrimental to tendon repair

Convalescent plasma in patients admitted to hospital with COVID-19 (RECOVERY): a randomised controlled, open-label, platform trial

SummaryBackground Azithromycin has been proposed as a treatment for COVID-19 on the basis of its immunomodulatoryactions. We aimed to evaluate the safety and efficacy of azithromycin in patients admitted to hospital with COVID-19.Methods In this randomised, controlled, open-label, adaptive platform trial (Randomised Evaluation of COVID-19Therapy [RECOVERY]), several possible treatments were compared with usual care in patients admitted to hospitalwith COVID-19 in the UK. The trial is underway at 176 hospitals in the UK. Eligible and consenting patients wererandomly allocated to either usual standard of care alone or usual standard of care plus azithromycin 500 mg once perday by mouth or intravenously for 10 days or until discharge (or allocation to one of the other RECOVERY treatmentgroups). Patients were assigned via web-based simple (unstratified) randomisation with allocation concealment andwere twice as likely to be randomly assigned to usual care than to any of the active treatment groups. Participants andlocal study staff were not masked to the allocated treatment, but all others involved in the trial were masked to theoutcome data during the trial. The primary outcome was 28-day all-cause mortality, assessed in the intention-to-treatpopulation. The trial is registered with ISRCTN, 50189673, and ClinicalTrials.gov, NCT04381936.Findings Between April 7 and Nov 27, 2020, of 16 442 patients enrolled in the RECOVERY trial, 9433 (57%) wereeligible and 7763 were included in the assessment of azithromycin. The mean age of these study participants was65·3 years (SD 15·7) and approximately a third were women (2944 [38%] of 7763). 2582 patients were randomlyallocated to receive azithromycin and 5181 patients were randomly allocated to usual care alone. Overall,561 (22%) patients allocated to azithromycin and 1162 (22%) patients allocated to usual care died within 28 days(rate ratio 0·97, 95% CI 0·87–1·07; p=0·50). No significant difference was seen in duration of hospital stay (median10 days [IQR 5 to >28] vs 11 days [5 to >28]) or the proportion of patients discharged from hospital alive within 28 days(rate ratio 1·04, 95% CI 0·98–1·10; p=0·19). Among those not on invasive mechanical ventilation at baseline, nosignificant difference was seen in the proportion meeting the composite endpoint of invasive mechanical ventilationor death (risk ratio 0·95, 95% CI 0·87–1·03; p=0·24).Interpretation In patients admitted to hospital with COVID-19, azithromycin did not improve survival or otherprespecified clinical outcomes. Azithromycin use in patients admitted to hospital with COVID-19 should be restrictedto patients in whom there is a clear antimicrobial indication

Biomechanical comparison of metatarsal head designs in first metatarsophalangeal joint arthroplasty

Background: Arthritis of the metatarsophalangeal (MTP) joint is characterized by loss of MTP joint range of motion (ROM) and pain. Joint arthroplasty is one treatment option, and while results can be satisfactory, there is still room for improvement. The aim was to use cadaveric model to compare the sagittal kinematics and articulating contact properties of 4 different first metatarsal head designs of an MTP joint implant. Methods: Six cadaveric feet were each prepared with a single modular first MTP joint total arthroplasty. A standard cyclic load, which induced hallux dorsiflexion, was applied and motion measured from high resolution images. Contact behavior was collected simultaneously using a pressure transducer. Data collected compared the native joint with 4 different reconstructed cases. Each reconstructed joint used a different metatarsal-head-component while reusing the same phalangeal component to compare the 4 alternative metatarsal head designs. Results: All reconstructed joints displayed greater ROM compared with the intact joint. Of the 4 metatarsal head components, the grooved, anatomical design demonstrated the greatest dorsiflexion when compared to the standard design, 31.6 degrees (SD ± 8.6 degrees), P < .05. All reconstructed joints displayed contact areas lower than the intact (~50%, P < .001). The grooved metatarsal-head-component experienced the least contact force (P < .015), and the eccentric component underwent the greatest contact pressure (P < .05) when compared to the intact case. Conclusions: In this study of a first metatarsophalangeal joint replacement design, ROM was shown to be better for the more anatomically designed metatarsal head, while contact properties did not vary across different designs. Clinical Relevance: This information may be useful in the development of new metatarsal components.9 page(s

Effect of partial versus complete circumferential repair on flexor tendon strength in cadavers

Purpose: This study investigated the strength of epitendinous repairs covering the palmar half of the tendon circumference only. Methods: Two hundred porcine tendons were harvested from pig feet and separated into 2 equal groups. Group 1 tendons were sutured with a 2-strand core repair and group 2 tendons were sutured with a 4-strand core repair. Each group was then divided into 5 equal subgroups (n=20). Four of the subgroups were sutured with 1 of the following epitendinous repairs: 50% simple running (50SR), complete simple running (100SR), 50% Silfverskiold (50SK), or complete Silfverskiold (100SK). One sub-group (0C) had no epitendinous repair. The core suture material was 3-0 braided polyester (Tricon; Tyco Healthcare, Dominican Republic), and the circumferential suture material was 6-0 polypropylene (Prolene, Sumerville, NJ). The tendons were mechanically strained to failure, and force data were recorded. Results: The 50SR and 50SK repairs significantly increased the force at 1-mm and 2-mm gap formation of both core repairs. The 50SR and 50SK repairs increased the ultimate force at failure of both core repairs by approximately 20%. Both 50% circumferential (50C) repairs increased repair strength at the points of initial gap formation more than at the point of ultimate force. The 50C repairs were approximately 50% as strong as the 100% circumferential (100C) repairs at 1-mm and 2-mm gap formation and approximately 70% as strong at the ultimate force of failure. Conclusions: The 50C repairs increased the tensile strength of 2-strand and 4-strand tendon repairs in vitro. The prevention of early gapping was more significant than the increase of strength at failure.6 page(s

A Detailed microscopic examination of alterations in normal anular structure induced by mechanical destabilization in an ovine model of disc degeneration

Study Design: Microstructural investigation of anular structure. Objective: To reveal the effect of mechanical destabilization on the anular architecture both locally and distantly. Summary Of Background Data: Several longitudinal ovine-induced disc degeneration studies have documented degenerative changes in disc components using histologic, biomechanical, and biochemical approaches; however, changes in intervertebral disc (IVD) microstructure have largely remained neglected. In recent years, the use of structurally relevant section planes has improved our understanding of disc microstructure, including the presence of significant bridging structures radially linking the lamellae. It has been suggested that the translamellar cross-bridges offer a mechanism by which the anular wall can adaptively remodel itself in response to a changing biomechanical microenvironment. Methods: IVDs harvested from lesion and sham-operated groups of Merino wethers were subjected to en face oblique and vertical sectioning. The macrostructural effect of the destabilization was examined in the vertically sectioned group with conventional histologic techniques. The second group was serially sectioned into 30-μm slices allowing a global examination of the anular microstructure in its fully hydrated state using a differential interference contrast microscope. Results: The previously described induced disc degeneration in the mid-inner anulus fibrosus (AF) and a spontaneous repair process in the outer AF was confirmed. Increased translamellar bridging was observed contralaterally to the lesion in the mechanically destabilized IVD and development of atypical broad bridging elements in the outer lamellae. Structural alterations in the lamellar anchorages to the cartilaginous endplates in destabilized IVDs, including lamellar branching and discontinuities atypical of normal lamellar attachments were also observed. Conclusion: The present investigation has offered a glimpse of an anular wall apparently capable of remodeling in response to perturbations in its normal mechanical environment. The translamellar cross-bridges undergo adaptations in structure, in response to altered stresses locally at the anular defect site but also distantly in the contralateral AF in the destabilized disc. It is currently not known whether such changes in anular microarchitecture, however, predispose the anulus to further mechanical damage or have a stabilizing role to play in this structure.9 page(s

Achilles and tail tendons of perlecan exon 3 null heparan sulphate deficient mice display surprising improvement in tendon tensile properties and altered collagen fibril organisation compared to C57BL/6 wild type mice

The aim of this study was to determine the role of the perlecan (Hspg2) heparan sulphate (HS) side chains on cell and matrix homeostasis in tail and Achilles tendons in 3 and 12 week old Hspg2 exon 3 null HS deficient (Hspg2Δ3 − ∕Δ3 −) and C57 BL/6 Wild Type (WT) mice. Perlecan has important cell regulatory and matrix organizational properties through HS mediated interactions with a range of growth factors and morphogens and with structural extracellular matrix glycoproteins which define tissue function and allow the resident cells to regulate tissue homeostasis. It was expected that ablation of the HS chains on perlecan would severely disrupt normal tendon organization and functional properties and it was envisaged that this study would better define the role of HS in normal tendon function and in tendon repair processes. Tail and Achilles tendons from each genotype were biomechanically tested (ultimate tensile stress (UTS), tensile modulus (TM)) and glycosaminoglycan (GAG) and collagen (hydroxyproline) compositional analyses were undertaken. Tenocytes were isolated from tail tendons from each mouse genotype and grown in monolayer culture. These cultures were undertaken in the presence of FGF-2 to assess the cell signaling properties of each genotype. Total RNA was isolated from 3–12 week old tail and Achilles tendons and qRT-PCR was undertaken to assess the expression of the following genes Vcan, Bgn, Dcn, Lum, Hspg2, Ltbp1, Ltbp2, Eln and Fbn1. Type VI collagen and perlecan were immunolocalised in tail tendon and collagen fibrils were imaged using transmission electron microscopy (TEM). FGF-2 stimulated tenocyte monolayers displayed elevated Adamts4, Mmp2, 3, 13 mRNA levels compared to WT mice. Non-stimulated tendon Col1A1, Vcan, Bgn, Dcn, Lum, Hspg2, Ltbp1, Ltbp2, Eln and Fbn1 mRNA levels showed no major differences between the two genotypes other than a decline with ageing while LTBP2 expression increased. Eln expression also declined to a greater extent in the perlecan exon 3 null mice (P < 0.05). Type VI collagen and perlecan were immunolocalised in tail tendon and collagen fibrils imaged using transmission electron microscopy (TEM). This indicated a more compact form of collagen localization in the perlecan exon 3 null mice. Collagen fibrils were also smaller by TEM, which may facilitate a more condensed fibril packing accounting for the superior UTS displayed by the perlecan exon 3 null mice. The amplified catabolic phenotype of Hspg2Δ3 − ∕Δ3 − mice may account for the age-dependent decline in GAG observed in tail tendon over 3 to 12 weeks. After Achilles tenotomy Hspg2Δ3 − ∕Δ3 − and WT mice had similar rates of recovery of UTS and TM over 12 weeks post operatively indicating that a deficiency of HS was not detrimental to tendon repair

Addition of Nitric Oxide Through Nitric Oxide-paracetamol Enhances Healing Rat Achilles Tendon

Nitric oxide is an important messenger molecule in many physiological processes. The addition of NO via NO-flurbiprofen enhances the material properties of healing tendon, however, flurbiprofen has a detrimental effect on healing. We asked if NO delivered by a cyclooxygenase 3 inhibitor (paracetamol/acetaminophen) would enhance healing in a rat Achilles tendon healing model. Rats were injected subcutaneously daily with NO-paracetamol, paracetamol or vehicle from two days before surgery to the day of tissue harvesting. Paracetamol had no effect on tendon healing compared with vehicle alone. NO-paracetamol did not change the failure load, but did decrease the water content, enhance the collagen content, reduce the cross-sectional area and improve the ultimate stress of healing tendon compared with paracetamol and vehicle. The collagen organization of the healing tendon in the NO-paracetamol group, as determined by polarized light microscopy, was enhanced. Our data suggests NO-paracetamol increases the total collagen content and enhances organization while decreasing the cross-sectional area of healing rat Achilles tendon and is consistent with human clinical trials where NO has improved the symptoms and signs of tendinopathy