Junction Failure Research Articles

Catastrophic Head-Neck Dissociation of a Modular Cementless Femoral Component.

We report two cases of modular head-neck junction failure involving the Stryker Accolade TMZF stem leading to sudden dissociation of the femoral head from the stem. Both patients presented with mechanical symptoms in the hip followed by pain and hip dysfunction. Disassembly of the head and deformation of the male taper were seen on preoperative radiographs. Intraoperatively, both patients had substantial metallosis with a markedly damaged taper requiring stem revision. We recommend regular clinical and radiographic surveillance of patients with the Stryker Accolade TMZF stem, especially those patients with pain and/or mechanical symptoms.

Controlling the wettability and adhesion of carbon fibers with polymer interfaces via grafted nanofibers

Interfacial properties in carbon fiber composites is one of the key parameters controlling their structural functionality. Here, we introduce a novel method to engineer carbon fiber-epoxy interfaces, via inclusion of nanofibers, towards higher interfacial strength and energy dissipation. In our method, thermally stabilized polyacrylonitrile (PAN) nanofibers are grafted onto carbon fibers via electro-spinning process, followed by nanofiber consolidation via solvent vapor and thermal treatment. These treatments partially dissolves nanofibers along the nanofiber-fiber interface and trigger entropic elasticity in nanofibers, thus, increasing the nanofiber-fiber interactions. The hybridization of carbon fibers with PAN nanofibers increased the interfacial shear strength (IFSS) by ∼48%, from 10.8 ± 2.6 to 15.9 ± 4.9 MPa. Postmortem fractography points to mechanical interlocking between nanofibers and epoxy and reinforcing effects of nanofibers in matrix as root causes of IFSS enhancement. As a result of adding nanofibers to carbon fiber, junction failure mode changes from a dominantly adhesive failure (at epoxy-fiber interface) to dominantly cohesive failure, and failure plane slightly shifts away from epoxy-fiber interface to within the epoxy. Compared to other types of whiskers grown on carbon fibers, such as CNTs, the method proposed here requires low temperatures (below 300 °C), during which no surface damages are expected to accumulate on carbon fibers.

"Surprise" Loading in Flexion Increases the Risk of Disc Herniation Due to Annulus-Endplate Junction Failure: A Mechanical and Microstructural Investigation.

Microstructural investigation of compression-induced herniation of the flexed lumbar disc. To provide a microstructural analysis of the mechanisms of annular wall failure in healthy discs subjected to flexion and a rate of compression comparable with the maximum rate at which the muscles of the spinal column can generate a force. Clinical evidence indicates the involvement of the endplate in herniation. It is known that both an elevated rate of compression and a flexed posture are necessary to cause disc failure either within the midspan of the annulus or at the annular-endplate interface. However, the question of what effect a sudden or "surprise" loading might have on the mode of failure is, as yet, unanswered. Twenty-four healthy mature ovine lumbar motion segments were compressed to failure in high physiological flexion (10º). This occurred over approximately 5 mm of crosshead displacement in 0.75 seconds that resulted in a displacement rate of 400 mm/min (defined as a "surprise" rate) and was intended to simulate the maximum rate at which the muscles of the spinal column can generate a force. The damaged discs were then analyzed microstructurally. Fifty-eight percent of discs suffered annular-endplate junction rupture, 25% suffered midspan annular rupture, and the balance of 17% endplate fracture. Microstructural analysis indicated that annular rupture initiated at the endplate apical ridge in the mid-to-outer region of the annulus in both annular-endplate and midspan annulus rupture. Motion segments subjected to a "surprise" loading rate are likely to fail via some form of annular rupture. Failure under such sudden loading occurs mostly via rupture of the annular-endplate junction and is thought to arise from a rate-induced mechanostructural imbalance between the annulus and the endplate. N/A.

Predicting the intermediate syndrome in organophosphorus poisoning.

Intentional organophosphorus (OP) poisoning is estimated to kill between 230,000 and 350,000 people a year worldwide, with a further 20,000 dying following accidental exposure.[1] The occurrence of a “type II paralysis,” usually proximal muscle paralysis, in survivors after the resolution of cholinergic features was recognized as complicating up to 18% of OP related admissions during an early case-series.[2] Senanayake and Karalliedde[3] classified this paralysis as the “intermediate syndrome” and described it as a distinct clinical entity on the basis of electromyographic (EMG) evidence of postsynaptic neuromuscular junction (NMJ) failure that occurred between 24 and 96 h after the resolution of the cholinergic crisis and prior to the onset expected for delayed neuropathy. The respiratory muscles are often affected and a prolonged period of ventilator support is required with all the associated risks of clinical complications and healthcare costs that such treatment entails. The pathophysiological mechanism of the syndrome remains obscure and empirical data are limited, although oxidative stress and changes in receptor-ligand binding kinetics have been reported. Muscle biopsies taken during the Bleecker et al. case series reported a limited degree of fiber necrosis that was considered to be insufficient to account for the clinical features observed during the study.[4] Biomarkers of oxidative stress, at least in erythrocytes, have been identified in patients with the intermediate syndrome.[5] A rat model of dimethoate poisoning described changes in skeletal muscle and lymphocyte, but not the central nervous system, nicotinic receptor binding function 48 h postexposure.[6] Several risk factors have been proposed for the development of intermediate syndrome. The type of OP and the severity of poisoning may be important. In a small prospective case series (n = 19, eight of which developed intermediate syndrome), Bleecker et al.,[4] noted that dimethyl OP agents were more commonly implicated in comparison with diethyl OP compounds. An observation later confirmed by Indira et al.[7] Bleecker et al.,[4] also observed that the clinical features and recovery correlated closely with EMG features and hypothesized that the NMJ dysfunction related to both pre- and post-synaptic changes. The degree of acetylcholinesterase inhibition has also found to be greater in individuals who went on to develop the syndrome.[4] The 1st day serum acetylcholinesterase activity does not, however, appear to predict the onset of the intermediate syndrome but may predict survival.[8] A finding not inconsistent with the observations reporting by Indira et al.,[7] of an increased relative risk of the intermediate syndrome in patients with a higher poisons severity score or reduced Glasgow Coma Scale. In this edition of the Journal, a prospective observational study by Kumar et al.[9] reported a significant rise in serum creatine phosphokinase (CPK) on admission and again, 48 h postadmission in three individuals with OP poisoning who subsequently developed intermediate syndrome compared to 72 h with OP poisoning who did not. Serum CPK concentrations were also noted to correlate with markers of poisoning severity such as the Peradeniya organophosphorus poisoning score, and the total dose of atropine administered, and inversely correlated with the degree of butyrylcholinesterase activity. These findings are consistent with those of Bhattacharyya et al.[10] who also described a correlation between admission CPK; the severity of poisoning and the risk of developing the intermediate syndrome. The study by Kumar et al.[9] has several strengths: The diagnosis of OP exposure was confirmed by cholinesterase activity measurement in each case; a standard treatment protocol was adhered to and the investigators excluded for the potential confounders that may cause an elevated serum CPK concentration, like seizures. The sample size of 75 makes this one of the larger studies focusing on the intermediate syndrome. The actual number of individuals who developed the syndrome was small. The authors acknowledge this limitation and note that this was due to the exclusion of those with severe poisoning. It remains unclear, therefore, if CPK is truly an independent risk factor for the intermediate syndrome or, instead, reflects disease severity; which in turn may be the principle risk factor for the onset of the syndrome. Determining the relative contributions of these and other potential risk factors for intermediate syndrome will require more research. A predictive test to risk-stratify those most likely to develop the syndrome is, however, a goal worth pursuing. If a successful test can be validated, using a resource that is readily available in the majority of healthcare settings then it should considerably aid the early identification of patients who are likely to require transfer to a center that can provide ventilator support over several days duration and also may facilitate further research into preventative therapies. The authors are to be commended for undertaking research into this problem, which is highly prevalent and disproportionately affects the more socioeconomically disadvantaged in our community. Financial support and sponsorship Nil. Conflicts of interest There are no conflicts of interest.

Preventing proximal junctional failure in long segmental instrumented cases of adult degenerative scoliosis using a multilevel stabilization screw technique.

Background:The authors sought to demonstrate the safety and effectiveness of the multilevel stabilization screw (MLSS) technique in decreasing the incidence of proximal junctional failure in long segmental instrumented fusions for adult degenerative scoliosis.Methods:Institutional review board approval was obtained and all patients with adult spinal deformity who underwent the MLSS technique were analyzed. A neuro-radiologist and spine-focused neurosurgeon not involved with the surgical treatment performed radiographic analysis. Proximal junctional angle was defined as the caudal endplate of the upper instrumented vertebra (UIV) to the cephalad endplate of two supradjacent vertebrae above the UIV. The UIV is defined as the most cephalad vertebra completed captured by the instrumentation. Abnormal proximal junctional kyphosis (PJK) was defined as proximal junctional sagittal Cobb angle >10 degrees and proximal junction sagittal Cobb angle at least 10 degrees greater than the preoperative measurement. The presence of both is criteria necessary to be considered abnormal.Results:Twenty patients with degenerative scoliosis underwent the MLSS technique with the upper-instrumented vertebrae in the proximal thoracic spine. Fifteen patients met inclusion criteria with greater than 12 months radiographic and clinical follow up. Three patients were excluded due to lack of follow up imaging and two patients were excluded due to the inability to measure the UIV. Age range was 44–84 years with a mean of 66. Eleven of the 15 patients were over the age of 60 at the time of surgery. The male-to-female ratio was 4:11. Body mass index (BMI) range was 24–44 with a mean of 31.5 units. The follow up period ranged from 14 to 58 months with an average follow up of 30 months. The mean change in Cobb angle at the proximal junction was 4.00 degrees with a range from -0.92 to 9.13 degrees. There were no fractures or instrumentation failures at or near the proximal junction. There was no revision surgeries performed for proximal junctional failure. Retrospective clinical questionnaires revealed that surgical expectations were met in 15 of 19 patients surveyed, 79%. One patient was not reachable for a postoperative phone interview. In patients who were not satisfied with their overall experience, the change in Cobb angle ranged from -0.92 to 9.13 degrees with an average change of 3.90 degrees. Whereas patients reporting an overall positive experience had a change in Cobb angle range from -0.12 to 8.07 degrees with an average change of 4.05 degrees.Conclusion:PJK and failure are well-recognized suboptimal outcomes of long-segmental fusions of the thoracolumbar spine that can lead to significant neurological morbidity and costly revision surgeries. With no known proximal junction failures to date, the MLSS technique has shown promising results in preventing adverse proximal junctional conditions and can be safely performed under fluoroscopy guidance. Future direction includes a comparative study establishing the relative risk of developing PJK with this novel technique versus a traditional long-segmental thoracolumbar fusion.

How Healthy Discs Herniate

Microstructural investigation of compression-induced disruption of the flexed lumbar disc. To provide a microstructural analysis of the mechanisms of annular wall failure in healthy discs subjected to flexion and an elevated rate of compression. At the level of the motion segment failure of the disc in compression has been extensively studied. However, at the microstructural level the exact mechanisms of disc failure are still poorly understood, especially in relation to loading posture and rate. Seventy-two healthy mature ovine lumbar motion segments were compressed to failure in either a neutral posture or in high physiological flexion (10°) at a displacement rate of either 2 mm/min (low) or 40 mm/min (high). Testing at the high rate was terminated at stages ranging from initial wall tearing through to facet fracture so as to capture the evolution of failure up to full herniation. The damaged discs were then analyzed microstructurally. Approximately, 50% of the motion segments compressed in flexion at the high rate experienced annulus or annulus-endplate junction failure, the remainder failed via endplate fracture with no detectable wall damage. The average load to induce disc failure in flexion was 18% lower (P < 0.05) than that required to induce endplate fracture. Microstructural analysis indicated that wall rupture occurred first in the posterior mid-then-outer annulus. Disc wall failure in healthy motion segments requires both flexion and an elevated rate of compression. Damage is initiated in the mid-then-outer annular fibers, this a likely consequence of the higher strain burden in these same fibers arising from endplate curvature. Given the similarity in geometry between ovine and human endplates, it is proposed that comparable mechanisms of damage initiation and herniation occur in human lumbar discs. N/A.

Tissue‐Engineered Cellular Neotendinous Constructs for Chronic Hernia Repair in a Rat (LB34)

Objective: Over 200,000 incisional hernia repairs are performed each year in the United States at a cost of over $2.5 billion. Currently, hernias are repaired using either alloplastic meshes or soft tissue-derived prostheses; however, recurrence rates remain 10-20% after primary repair and as high as 60% after repair of recurrent hernias. We have developed cellular neotendinous constructs (CNTs), scaffoldless 3-D tissue-engineered prostheses for hernia repair. Our CNTs integrate into the native muscle of the abdominal wall and allow infiltration of host cells, which may prevent junction failure and chronic prosthesis attenuation, the primary causes of hernia recurrence. The purpose of this preliminary study was to assess the potential of our CNTs as improved tissue prostheses for chronic hernia repair in a rat model. Methods: Bone marrow stromal cells were isolated from Fischer 344 rats and used to produce the CNT constructs. Two-centimeter incisional hernias were created along the abdominal midline in ten Fischer 344 rats and left unrepaired for one month. A single CNT was used to close each defect site and 56 days were allowed for recovery. Biomechanical analyses were performed using a novel burst pressure test. Results: After 56 days in vivo, our CNTs fully repaired seven of the ten hernias. When subjected to pressure testing, four of the repair sites resisted substantial pressures, bursting at a mean of 65 kPa, 57% of native abdominal wall burst pressure. Histological analysis of the repair sites indicated the formation of robust CNT-host muscle junctions. Figure 1. A single CNT (A) was implanted into each chronic hernia site (B&C). After 56 days, seven of the ten hernias had been closed (D). Figure 2. Of the seven repaired abdominal walls, four were able to withstand significant hydraulic pressure, bursting at 56% of the mean control pressure. Error bars indicate standard error. Conclusions: These data indicate that our CNTs warrant further study as tissue prostheses for ventral hernia repair. In future work, we will develop more durable CNTs which we hypothesize will provide improved repairs with biomechanical properties approaching those of native abdominal wall.

Letter to the Editor: In Response to “Modular Taper Junction Corrosion and Failure: How to Approach a Recalled Total Hip Arthroplasty Implant”

Letter to the Editor: In Response to “Modular Taper Junction Corrosion and Failure: How to Approach a Recalled Total Hip Arthroplasty Implant”

High rate of fracture in the cementless modular Extrême™ (Mark I) femoral prosthesis in revision total hip arthroplasty: 33 cases at more than 5 years’ follow-up

The modular concept has been recommended in femoral revision surgery with extensive bone loss, but entails mechanical complications: disassembly and fracture. The present retrospective study assessed the Mark I Extrême™ modular prosthesis at a minimum 5 years' follow-up. A cementless modular femoral stem facilitates revision in case of extensive bone loss, providing satisfactory results without risk of junction failure. Thirty-three prostheses presenting aseptic loosening, including 3 with periprosthetic fracture, in 23 female and 9 male patients, with a mean age of 65 years (range, 49-83 years), were reviewed at a mean 6.3 years' follow-up (range, 5-9 years). Bone loss was assessed on the SOFCOT (17/33 grade 3 or 4) and Paprosky classifications (19/33 grade III or IV). One patient died; another was lost to follow-up, leaving 31 hips for analysis. Clinical assessment comprised Postel Merle d'Aubigné (PMA) and Harris Hip scores (HHS); radiological assessment used the Engh score and corticomedullary index (CMI). There were 15 complications requiring surgery: 9 (27%) unrelated to the implant (1 hematoma, 2 infections, 2 dislocations, 1 femoral non-union, 3 asymptomatic trochanteric non unions) and 6 (18%) implant-related (four 3-level fractures and 2 epiphyseal-metaphyseal disassemblies, requiring 3 total exchanges and 3 proximal component replacements). PMA and HHS scores showed significant improvement, PMA rising from 10.4 (6-18) to 14.4 (11-18) and HHS from 50 (19-88) to 80.9 (52-100). Bone regrowth was "certain" on the Engh classification in 11 cases (44%). There was no diaphyseal component subsidence, even in case of fracture or dissociation. CMI at the 3 junctions between the 4 quarters of the stem showed no significant change: 32.9 and 32.7, 41.2 and 38.7, and 41.6 and 39.9 respectively. Six-year survivorship was 81% (95% CI: 68-94%). In other series for the same type of implant, the rates of fracture (always metaphyseal-diaphyseal) were much lower: 0.8-3.8%. This stem ensures diaphyseal fixation in case of extensive bone loss, but incurs excessive risk of disassembly and fracture.

Modular Taper Junction Corrosion and Failure: How to Approach a Recalled Total Hip Arthroplasty Implant

Corrosion at the modular neck-stem taper junction has become an increasingly important topic as several reports have identified this couple as a possible source for early failure with findings similar to failed metal-on-metal hip arthroplasties. Recently, two different modular stem systems from a single manufacturer were voluntarily recalled due to concerns of failure of the modular taper junction. We discuss how to approach the diagnosis and management of patients with these particular stem systems. We further reviewed the literature to evaluate whether this is a manufacturer-specific defect or indicative of a broader trend. Recent studies appear to implicate the basic design of the neck-stem taper junction, rather than a single manufacturer, which is at high risk for fretting and corrosion.

Utility of Trephine Reamers in Revision Hip Arthroplasty

Powered trephines used over a femoral component to disrupt the bone component interface can yield acceptable clinical and radiographic outcomes while minimizing direct mechanical injury and indirect thermal necrosis. Thirty-six patients required trephining for fractured stems (16), infection (8), malposition (7), modular junction failure (4), and acetabular exposure (1). Harris Hip Scores (HHS), radiographic healing, and complications were assessed at a follow-up of 50.01 mo. Mean HHS increased from 46.61 preoperatively to 87.78 postoperatively (p<.0001). Two patients suffered spontaneous postoperative periprosthetic fractures in the region of the trephined bone at 3 mo and 4 mo postoperatively. Despite undergoing ORIF with locked plates, they both re-fractured with necrotic bone observed at the time of revision. There is a 5.6% incidence of femoral shaft fractures near the region of trephined bone within 1 year of surgery. Given the location of these fractures, thermal necrosis may have occurred and consideration should be given to distally bypassing the region of the femur that has been trephined.

MRI Characterization of Paranodal Junction Failure and Related Spinal Cord Changes in Mice

The paranodal junction is a specialized axon-glia contact zone that is important for normal neuronal activity and behavioral locomotor function in the central nervous system (CNS). Histological examination has been the only method for detecting pathological paranodal junction conditions. Recently, diffusion tensor MRI (DTI) has been used to detect microstructural changes in various CNS diseases. This study was conducted to determine whether MRI and DTI could detect structural changes in the paranodal junctions of the spinal cord in cerebroside sulfotransferase knock-out (CST-KO) mice. Here, we showed that high-resolution MRI and DTI characteristics can reflect paranodal junction failure in CST-KO mice. We found significantly lower T1 times and significantly higher T2 times in the spinal cord MRIs of CST-KO mice as compared to wild-type (WT) mice. Spinal cord DTI showed significantly lower axial diffusivity and significantly higher radial diffusivity in CST-KO mice as compared to WT mice. In contrast, the histological differences in the paranodal junctions of WT and CST-KO mice were so subtle that electron microscopy or immunohistological analyses were necessary to detect them. We also measured gait disturbance in the CST-KO mice, and determined the conduction latency by electrophysiology. These findings demonstrate the potential of using MRI and DTI to evaluate white matter disorders that involve paranodal junction failure.

Taper junction failure in large-diameter metal-on-metal bearings

ObjectivesAn ongoing prospective study to investigate failing metal-on-metal hip prostheses was commenced at our centre in 2008. We report on the results of the analysis of the first consecutive 126 failed mated total hip prostheses from a single manufacturer.MethodsAnalysis was carried out using highly accurate coordinate measuring to calculate volumetric and linear rates of the articular bearing surfaces and also the surfaces of the taper junctions. The relationship between taper wear rates and a number of variables, including bearing diameter and orientation of the acetabular component, was investigated.ResultsThe measured rates of wear and distribution of material loss from the taper surfaces appeared to show that the primary factor leading to taper failure is the increased lever arm acting on this junction in contemporary large-diameter metal-on-metal hip replacements.ConclusionsOur analysis suggests that varus stems, laterally engaging taper systems and larger head diameters all contribute to taper failure.

Biomechanics of the front abdominal wall as a potential factor leading to recurrence with laparoscopic ventral hernia repair

Intraabdominal pressure often is blamed as the cause of mesh-fascia junction failure after laparoscopic ventral hernia repair. Stretching of the mesh during a cough or defecation may lead to recurrence. Little is known about the movements of mesh in the abdominal cavity after this operation. This study investigated the front abdominal wall to describe its elasticity in vivo and searched for elongations that possibly stretched an implanted mesh, thereby causing fixation failure and subsequent recurrence. To measure front abdominal wall elongations, a model of fascia movements was created. Eight healthy volunteers were measured during exercise to determine the extent of elongations in their front abdominal wall. Videos were analyzed in three positions to create a mathematical shell structure. A computerized model based on the net movement of nodes was calculated to determine the axes and values for maximum elongations. The largest average elongations were measured for the upper midline (32.08%) and the transverse line in the low lateral area (34.06%). The maximum values for these lines were larger than 100% for the middle line (133.78%) and exceeded 50% for the entire middle line. The values for the horizontal lines did not reach 10% at any level. According to these data, areas of both high and low elasticity were defined. The presented experiment adds new parameters to the understanding of in vivo mesh behavior. Elongation of the front abdominal wall may stretch implanted mesh and could be a cause of recurrence in cases of insufficient fixation.

Laser Saphenous Ablations in More Than 1,000 Limbs With Long-Term Duplex Examination Follow-Up

The goal of this study was to evaluate the duplex results of endovenous laser ablation in the treatment of incompetent great saphenous veins (GSV) and small saphenous veins (SSV) with at least 1-year follow-up. A retrospective registry was entered by 11 centers from Europe and America, organized by the International Endovenous Laser Working Group. Data concerning 1,020 limbs in patients with incompetence of the GSV and/or SSV, treated with the Endovenous Laser Ablation (EVLA) procedure, were collected. EVLA failures were defined on duplex imaging as reflux confined to the saphenofemoral or saphenopopliteal junction, reflux confined to the main saphenous trunk, or reflux of both junction and main trunk (totally patent saphenous vein) were analyzed at one or more years postoperatively. The mean age of patients was 54 ± 5 years (range: 18-91 years). The average body mass index was 25. There was a paucity of severe complications: One case of third-degree skin burn, six patients with postsurgical deep vein thrombosis (0.6%), and 27 cases of sensory nerve damage (2.7%). At 1-year, the rate of complete occlusion of the saphenous trunk was 93.1%. There were 79 cases of treatment failures as evidenced by duplex: 22 isolated junction failures (2.2%), 44 isolated trunk failures (4.4%), and 13 totally patent veins (1.3%). Two-year duplex results were reported for 329 limbs with the identification of 19 new cases of failure. No new cases of failure were reported at 3-year follow-up of 130 limbs. Cumulative failure rates estimated by Kaplan-Meier analysis were 7.7% at 1-year and 13.1% at 2- and 3-year follow-up. On the basis of a duplex scan performed at least 1-year post-treatment, this multicenter registry confirms the safety and efficacy of the EVLA procedure in the treatment of GSV and SSV reflux. Considering the continued failure rate documented in the present study, an annual follow-up by duplex is recommended to 2 years after EVLA.

Edge current induced failure of semiconductor PN junction during operation in the breakdown region of electrical characteristic

Typical blocking I–V characteristics are shown and analyzed for PN junctions exhibiting a breakdown region above 1000 V from commercial diodes and power MOSFETs. The leakage reverse current of PN junctions from commercial silicon devices available at this time has a flowing component at the semiconductor–passivant material interface around the junction edge. Part of the plotted experimental current–voltage characteristic fits to linear variation and deviation from this variation at higher applied voltage is attributed to non-controlled current flow in the interfacial layer, between the silicon and passivating material from the junction periphery. The thin interfacial layer including atomic layers both from the semiconductor and passivating dielectric material with fixed charges has imperfections resulted from the junction passivation process. For controlled-avalanche PN junctions no deviation from linear voltage dependence of the reverse current is possible until breakdown region practically at right knee appears. For other PN junctions deviation of the reverse current from linear variation results in a breakdown region with round knee and still with visible voltage dependence at current increase. Such soft breakdown region caused by the phenomena in the interfacial layer is exhibited at lower applied reverse voltage than the expected one for breakdown caused by charge carrier avalanche multiplication at the junction. Operation even for short in the soft breakdown region can lead to PN junction failure and for this reason, a maximum working permissible reverse voltage is specified in device data sheet with a value under the breakdown region. Junction failure consists in significantly lower reverse voltage than the initial one or even electrical short-circuit caused by a spot of material degradation in the interfacial layer from the junction periphery. Operation of the controlled-avalanche diode in the breakdown region is possible only for single pulse of short duration and at junction temperature not higher than 175 °C. Above 150–175 °C even for controlled-avalanche diodes deviation from linear variation of the reverse current has been observed and soft breakdown region can appear before the expected avalanche breakdown. Device failure after operation in the breakdown region, caused by spot of material degradation at the junction periphery has occurred in such conditions. For high voltage commercial power MOSFETs operation in the avalanche breakdown region is limited to 150 °C.

Non-muscarinic Therapeutic Targets for Acute Organophosphorus Poisoning

Organophosphorus (OP) pesticides are a broad class of acetylcholinesterase inhibitors that are responsible for tremendous morbidity and mortality worldwide, contributing to an estimated 300,000 deaths annually. Current pharmacotherapy for acute OP poisoning includes the use of atropine, an oxime, and benzodiazepines. However, even with such therapy, the mortality from these agents is as high as 40%. It is increasingly recognized that not all OPs are the same. Significant differences exist in their toxicity, lipophilicity, and response to oxime therapy. Other non-muscarinic effects of OP pesticides exist, such as acute and chronic neuromuscular junction failure and central respiratory failure. In part because most of the mortality from these chemicals takes place in the developing world, little National Institutes of Health (NIH) research has been directed towards these agents. However, the similar mechanism of action of OP pesticides and the military nerve agents, along with increasing concerns about chemical terrorism has lead to the formation of the NIH Countermeasures Against Chemical Threats (CounterACT) Program. As part of the CounterACT Program, the NIH has recently designated six OP pesticides as "threat agents". This concept paper describes some of the knowledge gaps related to non-muscarinic effects of OP pesticides and highlights needed areas of further research. Leveraging the current NIH interest in these chemicals to medical necessities in the developing world offers the possibility of delivering new therapeutics where they are needed on a daily basis.

Reliability of SiGe HBTs for Power Amplifiers&amp;#x2014;Part II: Underlying Physics and Damage Modeling

This paper presents the underlying physics and modeling of aggressively biased cascode SiGe heterojunction bipolar transistor power amplifier (PA) cores under large-signal operating conditions. The damage characteristics observed during RF operation, particularly the base leakage and collector-base (CB) junction failure, are investigated in detail using dc stress methods. Base leakage was characterized across geometry, voltage, and current conditions, and a damage model is purposed based on Shockley-Read-Hall theory and the reaction-diffusion equation. This model is used to predict damage under aggressive RF operations, in order to extract the operational lifetime of SiGe PAs. The onset of CB junction failure was modeled using the current-gain collapse model, and it accurately captures the failure threshold current I Fail observed during RF stress.

Congenital Hypomyelinating Neuropathy with Lethal Conduction Failure in Mice Carrying the Egr2 I268N Mutation

Mouse models of human disease are helpful for understanding the pathogenesis of the disorder and ultimately for testing potential therapeutic agents. Here, we describe the engineering and characterization of a mouse carrying the I268N mutation in Egr2, observed in patients with recessively inherited Charcot-Marie-Tooth (CMT) disease type 4E, which is predicted to alter the ability of Egr2 to interact with the Nab transcriptional coregulatory proteins. Mice homozygous for Egr2(I268N) develop a congenital hypomyelinating neuropathy similar to their human counterparts. Egr2(I268N) is expressed at normal levels in developing nerve but is unable to interact with Nab proteins or to properly activate transcription of target genes critical for proper peripheral myelin development. Interestingly, Egr2(I268N/I268N) mutant mice maintain normal weight and have only mild tremor until 2 weeks after birth, at which point they rapidly develop worsening weakness and uniformly die within several days. Nerve electrophysiology revealed conduction block, and neuromuscular junctions showed marked terminal sprouting similar to that seen in animals with pharmacologically induced blockade of action potentials or neuromuscular transmission. These studies describe a unique animal model of CMT, whereby weakness is due to conduction block or neuromuscular junction failure rather than secondary axon loss and demonstrate that the Egr2-Nab complex is critical for proper peripheral nerve myelination.

Modular Femoral Stem-Sleeve Junction Failure After Primary Total Hip Arthroplasty

The total hip prosthesis has evolved from the initial monoblock system developed by Charnley. Modularity of both the femoral and acetabular components, which allows the surgeon to assemble the prostheses just before or during the course of implantation, has now become standard. Modularity increases the number of implant parameter variables, allowing semicustom devices to be constructed. Component interfaces, however, are subject to significant stresses, micromotion manifesting as fretting, may produce wear debris, and at times may experience macromotion leading to catastrophic failure. We report 3 cases of stem-sleeve junction failure in otherwise uncomplicated primary total hip arthroplasties. Two of the failures occurred in the S-ROM (Joint Medical Products, Stamford, Conn) femoral stem design and the other in an Apex stem (Omni Life Science, Raynham, Mass). To our knowledge, there have been no previous reports of clinical failures at femoral stem-sleeve junction.