LAC+USC Medical Center

Introduction Periprosthetic joint infection (PJI) is one of the most challenging and frequent complications after lower-extremity joint (hip and knee) arthroplasty. However, there is no single accepted set of diagnostic criteria for PJI. Various definitions have been proposed; however, none have been widely adopted. Furthermore, some of these definitions disagree with each other [14]. Therefore, a workgroup convened by the Musculoskeletal Infection Society (MSIS) analyzed the available evidence to propose a new definition for PJI. A summary of recommendations of those in attendance at a premeeting workshop of the 21st Annual Meeting of the MSIS on August 4, 2011, pertaining to the definition of PJI is outlined below. Existing published data on the definition of PJI was discussed by e-mail in the preceding 6 months by the executive members of the MSIS and a group of experts with known interest in this field. The intention of this proposal is to have a “gold standard” definition for PJI that can be universally adopted by all physicians, surveillance authorities (including the Centers for Disease Control, medical and surgical journals, the medicolegal community), and all involved in management of PJI. The panel acknowledged, in certain low-grade infections (ie, Propionibacterium acnes), several of these criteria may not be routinely met despite the presence of PJI. Using this definition, clinicians can be confident in their diagnosis and therefore provide appropriate treatment. Additionally, adoption of this definition for research purposes will allow for consistency between studies and potential improvement of the quality of the published body of evidence. Definition of Periprosthetic Joint Infection Based on the proposed criteria, definite PJI exists when: There is a sinus tract communicating with the prosthesis; or A pathogen is isolated by culture from at least two separate tissue or fluid samples obtained from the affected prosthetic joint; or Four of the following six criteria exist: Elevated serum erythrocyte sedimentation rate (ESR) and serum C-reactive protein (CRP) concentration, Elevated synovial leukocyte count, Elevated synovial neutrophil percentage (PMN%), Presence of purulence in the affected joint, Isolation of a microorganism in one culture of periprosthetic tissue or fluid, or Greater than five neutrophils per high-power field in five high-power fields observed from histologic analysis of periprosthetic tissue at ×400 magnification. PJI may be present if fewer than four of these criteria are met. Considerations Microbiologic Testing It is imperative that tissue for culture be obtained from representative periprosthetic tissue or fluid. To limit the risk of contamination, each sample should be taken with separate, sterile instruments. The definition of phenotypically identical organisms should be based on phenotypic similarities and in vitro antimicrobial susceptibility testing since confirmation of genetic identity is not routinely performed on clinical isolates. We recommend that at least three and no more than five periprosthetic specimen culture samples are taken and incubated in an aerobic and anaerobic environment. Fungal and mycobacterial cultures should not be performed routinely and reserved to higher-risk scenarios. The time of culture incubation has not been standardized yet. Isolation of a single low-virulence pathogen such as coagulase-negative Staphylococcus, P. acnes, or Corynebacteria in the absence of other criteria is not believed to represent a definite infection. Isolation of a single virulent organism such as S. aureus may represent a PJI. Furthermore, recent evidence has identified that certain tests, such as Gram stain, of periprosthetic tissue or fluid are not sensitive in diagnosing PJI [7]. Serum Tests Based on previous publications, an ESR of greater than 30 mm/hour and a CRP of greater than 10 mg/L would represent elevated levels [11, 15]. However, it is important to note there are variations in measuring these markers between laboratories. Furthermore, the level of these serum markers is affected by age, sex, and medical comorbidities of the patient. It has also been reported these markers can be elevated for approximately 30 to 60 days in the immediate postoperative period [3, 9]. Synovial Tests Multiple studies have provided thresholds for synovial leukocyte count and PMN% in the differential. In the chronically infected knee arthroplasty, these values have been reported from 1100 to 4000 cells/μL and 64% to 69%, respectively [5, 8, 16]. In patients with acute infections, the levels of synovial cell count and PMN% are much higher (approximately 20,000 cells/μL and 89%, respectively). Acute infections are defined as less than 3 months from index surgery or from the onset of symptoms [1]. The levels of synovial cell count and PMN% in the infected hip arthroplasty are not well delineated. A sole study has provided a threshold of 3000 cells/μL for leukocytes and 80% for PMN% for the infected hip arthroplasty [15]. None of these studies have included patients with underlying inflammatory arthropathies and related diseases. Current research is proceeding to provide more definitive thresholds for all patients. Histology Examination of periprosthetic tissues for evidence of neutrophils has been traditionally conducted by specially trained musculoskeletal pathologists. Histologic examination consequently may be operator dependent. It is therefore incumbent on surgeons to ensure their pathologists are in agreement with the diagnostic criteria for PJI. When examining for the presence of neutrophils, the histopathologist should disregard neutrophils entrapped in superficial fibrin or adherent to endothelium or small veins. Also, caution should be exercised in analyzing this test in cases where elevated neutrophil count might be expected, such as recent periprosthetic fractures or inflammatory arthropathy. Future Developments This proposed definition was based on current evidence supporting the role of various tests in diagnosis of PJI that are available in the literature. We recognize there are numerous other tests currently being evaluated, including measurement of CRP from the synovial fluid [12], synovial leukocyte esterase [13], sonication of explanted prosthetics [17], and molecular techniques such as PCR [10] and other molecular markers such as IL-6 [2, 4, 6]. As these or other techniques become validated and widely available, the currently proposed definition may require modification. Acknowledgments We thank the following individuals for their involvement and invaluable input throughout the development of this document: Robert Barrack MD, Keith Berend MD, Sandra Berrios-Torres (from Centers for Disease Control and Prevention), Kevin Bozic MD, John Esterhai MD, Ryan Fagan (from Centers for Disease Control and Prevention), Thomas Fehring MD, Terry Gioe MD, Teresa Horan (from Centers for Disease Control and Prevention), Steven Kurtz PhD, Bas Masri MD, Arvind Nana MD, Douglas Osmon MD, John Segreti MD, and Mark Spangehl MD.

Multifactorial mechanisms underlying late-onset Alzheimer's disease (LOAD) are poorly characterized from an integrative perspective. Here spatiotemporal alterations in brain amyloid-β deposition, metabolism, vascular, functional activity at rest, structural properties, cognitive integrity and peripheral proteins levels are characterized in relation to LOAD progression. We analyse over 7,700 brain images and tens of plasma and cerebrospinal fluid biomarkers from the Alzheimer's Disease Neuroimaging Initiative (ADNI). Through a multifactorial data-driven analysis, we obtain dynamic LOAD-abnormality indices for all biomarkers, and a tentative temporal ordering of disease progression. Imaging results suggest that intra-brain vascular dysregulation is an early pathological event during disease development. Cognitive decline is noticeable from initial LOAD stages, suggesting early memory deficit associated with the primary disease factors. High abnormality levels are also observed for specific proteins associated with the vascular system's integrity. Although still subjected to the sensitivity of the algorithms and biomarkers employed, our results might contribute to the development of preventive therapeutic interventions.

Acinetobacter is a complex genus, and historically, there has been confusion about the existence of multiple species. The species commonly cause nosocomial infections, predominantly aspiration pneumonia and catheter-associated bacteremia, but can also cause soft tissue and urinary tract infections. Community-acquired infections by Acinetobacter spp. are increasingly reported. Transmission of Acinetobacter and subsequent disease is facilitated by the organism's environmental tenacity, resistance to desiccation, and evasion of host immunity. The virulence properties demonstrated by Acinetobacter spp. primarily stem from evasion of rapid clearance by the innate immune system, effectively enabling high bacterial density that triggers lipopolysaccharide (LPS)-Toll-like receptor 4 (TLR4)-mediated sepsis. Capsular polysaccharide is a critical virulence factor that enables immune evasion, while LPS triggers septic shock. However, the primary driver of clinical outcome is antibiotic resistance. Administration of initially effective therapy is key to improving survival, reducing 30-day mortality threefold. Regrettably, due to the high frequency of this organism having an extreme drug resistance (XDR) phenotype, early initiation of effective therapy is a major clinical challenge. Given its high rate of antibiotic resistance and abysmal outcomes (up to 70% mortality rate from infections caused by XDR strains in some case series), new preventative and therapeutic options for Acinetobacter spp. are desperately needed.

Forty newborn infants, median age 9 minutes, turned their eyes and heads to follow a series of moving stimuli. Responsiveness was significantly greater to a proper face pattern than to either of two scrambled versions of the same stimulus or to a blank. The demonstration of such consistent response differences suggests that visual discriminations are being made at this early age. These results imply that organized visual perception is an unlearned capacity of the human organism. The preference for the proper face stimulus by infants who had not seen a real face prior to testing suggests that an unlearned or "evolved" responsiveness to faces may be present in human neonates.

One-hundred-ninety-four eligible and evaluable patients with histologically confirmed locally unresectable adenocarcinoma of the pancreas were randomly assigned to therapy with high-dose (6000 rads) radiation therapy alone, to moderate-dose (4000 rads) radiation + 5-fluorouracil (5-FU), and to high-dose radiation plus 5-FU. Median survival with radiation alone was only 51/2 months from date of diagnosis. Both 5-FU-containing treatment regimens produced a highly significant survival improvement when compared with radiation alone. Forty percent of patients treated with the combined regimens were still living at one year compared with 10% of patients treated with radiation only. Survival differences between 4000 rads plus 5-FU and 6000 rads plus 5-FU were not significant with an overall median survival of ten months. Significant prognostic variables, in addition to treatment, were pretreatment performance status and pretreatment CEA level.

We estimated the prevalences of Helicobacter pylori (formerly called Campylobacter pylori) infection and histologic gastritis in 113 asymptomatic persons, using endoscopic biopsy of the gastric antrum and corpus. Unsuspected lesions, mainly mucosal erosions, were revealed at endoscopy in 16 subjects (14 percent). Gastritis was found in 42 subjects (37 percent), of whom 36 (32 percent of the total) were found to be infected with H. pylori on the basis of hematoxylin-eosin staining. H. pylori was not found in any of the 71 subjects with normal histologic features. Gastritis and H. pylori were noted in both the antrum and corpus in 75 percent of those infected (n = 27). The prevalence of H. pylori infection increased from 10 percent (2 of 20 subjects) in those between the ages of 18 and 29, to 47 percent (7 of 15) in those between the ages of 60 and 69, but the effect of age did not reach statistical significance. The prevalence of gastritis increased significantly with advancing age. Stepwise logistic regression analysis revealed that the relative risk for H. pylori infection associated with recent (within six months) antibiotic use was 5.8 (95 percent confidence interval, 1.5 to 22.1), whereas the relative risk was 6.5 (95 percent confidence interval, 1.4 to 29.2) for those who had never used bismuth compounds. We conclude that histologic gastritis and H. pylori infection commonly occur in the stomach of apparently normal persons and increase in prevalence with advancing age. All the subjects with H. pylori infection had gastritis, suggesting a possible etiologic role for the bacterium in the histologic lesion.

The increase in lactate (L) and pyruvate (P) content of arterial blood during experimental and clinical shock states and the extent to which such increases serve as measures of oxygen deficit and irreversible injury were investigated on an empirical basis. A standardized method for production of hemorrhagic shock in the Wistar rat was employed. During a 4-hour bleeding period, oxygen consumption of the rat was reduced to approximately 40% of control value, pH was reduced from 7.39 to 7.08, and a concurrent increase in L from 0.80 to 6.06 m m and in P from 0.07 to 0.18 m m were observed. Cumulative oxygen debt correlated with log L (r = 0.50; P < 0.0005) and both were significantly related to survival. Correlation of cumulative oxygen debt and survival, both with P and with computed values of the lactate pyruvate ratio (L/P) and excess lactate (XL), were of no higher magnitude. Partial correlation analysis demonstrated that neither the measurement of P nor the computation of L/P or XL improved predictability. In 142 patients who presented with clinical manifestation of circulatory shock and of whom 62 survived and 80 died, the best empirical discrimination between survivors and those who died was provided by measurement of L, which failed only 11% of the time. This was confirmed by discriminant function analysis in which the percentage probability of misclassification based on L was 12% whereas this probability increased to 21% with L/P and 19% with XL. The combination of XL and L/P with L failed to improve discrimination. In this series of patients, L served as a sensitive predictor; as L increased from 2.1 to 8.0 m m , the estimated probability of survival decreased from 90 to 10%. These studies corroborate that L alone serves as a reliable indicator, but neither the measurement of P nor the computation of L/P or XL was shown to improve either the reliability of L as a measure of cumulative oxygen debt or its value as a prognosticator of survival during shock states.

Human papilloma virus (HPV) DNA sequences have been detected in paraffin-embedded tissue using an enzymatic in vitro amplification technique known as the polymerase chain reaction. Amplification of a HPV DNA sequence before its detection with a cDNA probe significantly increases the rapidity as well as the sensitivity of detection such that a single 5-10-micron thick paraffin-embedded tissue section can be analyzed within 24 h. The assay specifically detected HPV 16 or 18 without crossreactivity with HPV 6 or 11. As few as 20 viral copies could be detected. The rapid and sensitive analysis of HPV in normal and pathological tissues using this technique may contribute significantly to identifying the role of HPV as a risk factor in carcinoma.

To determine whether insulin resistance occurs in polycystic ovarian disease (PCO) in the absence of obesity and acanthosis nigricans, circulating levels of insulin in response to oral glucose administration were measured in 10 nonobese PCO patients without acanthosis nigricans and in 10 normal women matched for weight and height. Mean serum testosterone (T), androstenedione (A), dehydroepiandrosterone (D), D sulfate, and LH levels were significantly elevated in the PCO patients compared to those in control subjects. In PCO patients, the mean +/- SE basal insulin level (18.7 +/- 2.9 microU/ml) and the sum of the insulin levels in response to glucose (674 +/- 119 microU/ml) were significantly greater than those in the control group (11.0 +/- 0.8 microU/ml and 248 +/- 29 microU/ml, respectively). In all subjects, serum levels of T and A, but not D and D sulfate, were significantly correlated to basal insulin levels and insulin sums. Serum cortisol, GH, and PRL levels were similar in both groups. These results indicate that in PCO, a significant degree of insulin resistance exists, which clearly is not related to obesity. The positive correlation of serum T and A levels to circulating insulin levels in this study suggests that the insulin resistance in PCO may be, in part, a consequence of hyperandrogenism.

Nonhuman primate and human studies have suggested that populations of neurons in the posterior parietal cortex (PPC) may represent high-level aspects of action planning that can be used to control external devices as part of a brain-machine interface. However, there is no direct neuron-recording evidence that human PPC is involved in action planning, and the suitability of these signals for neuroprosthetic control has not been tested. We recorded neural population activity with arrays of microelectrodes implanted in the PPC of a tetraplegic subject. Motor imagery could be decoded from these neural populations, including imagined goals, trajectories, and types of movement. These findings indicate that the PPC of humans represents high-level, cognitive aspects of action and that the PPC can be a rich source for cognitive control signals for neural prosthetics that assist paralyzed patients.

Abstract A standardized, reproducible Ivy bleeding time technic has been described which permits one to obtain accurate bleeding time data in man. The technic was used to standardize an aspirin tolerance test in which 60 normal males had a control bleeding time; were given, on a double blind basis, either placebo or 1 Gm. of aspirin, and had a second bleeding time 2 hours later. The control values were: mean, 5 min.; mean ± 2 st. dev., 2 min., 30 sec. to 10 min. The values after placebo were: mean, 5 min., 30 sec.; mean ± 2 st. dev., 2 min., 30 sec. to 11 min. The values after aspirin were: mean, 9 min., 30 sec.; mean ± 2 st. dev., 4 min. to 21 min. The difference between the mean bleeding time after placebo and after aspirin was highly significant (p < 0.001). The distribution of the bleeding times after aspirin suggested that normal subjects do not respond to aspirin as a single population. The degree of prolongation of the bleeding time and the large size of the drops of blood observed in some subjects suggested to us that small amounts of aspirin may exert a significant effect upon hemostasis in normal individuals.

Immunoblastic lymphadenopathy, although it resembles Hodgkin's disease, is a distinct, hyperimmune disorder apparently of the B-cell system. In 32 cases, it was characterized by a morphologic triad: proliferation of arborizing small vessels; prominent immunoblastic proliferations; and amorphous acidophilic interstitial material. Clinically, it is manifested by fever, sweats, weight loss, occasionally a rash, generalized lymphadenopathy and often hepatosplenomegaly. There is a consistent polyclonal hyperglobulinemia and often hemolytic anemia. The course of the disease is usually progressive, with a median survival of 15 months in 18 fatal cases. The cellular proliferation appears benign morphologically in the pretherapy biopsies and in 10 of 12 available autopsy cases. In three cases the process evolved into a lymphoma of immunoblasts, immunoblastic sarcoma. The basic process appears to be a non-neoplastic hyperimmune proliferation of the B-cell system involving an exaggeration of lymphocyte transformation to immunoblasts and plasma cells that may be triggered by a hypersensitivity reaction to therapeutic agents.

The various proposed DHT routing algorithms embody several different underlying routing geometries. These geometries include hypercubes, rings, tree-like structures, and butterfly networks. In this paper we focus on how these basic geometric approaches affect the resilience and proximity properties of DHTs. One factor that distinguishes these geometries is the degree of flexibility they provide in the selection of neighbors and routes. Flexibility is an important factor in achieving good static resilience and effective proximity neighbor and route selection. Our basic finding is that, despite our initial preference for more complex geometries, the ring geometry allows the greatest flexibility, and hence achieves the best resilience and proximity performance.

Abstract The heterogeneity of neurodegenerative diseases is a key confound to disease understanding and treatment development, as study cohorts typically include multiple phenotypes on distinct disease trajectories. Here we introduce a machine-learning technique—Subtype and Stage Inference (SuStaIn)—able to uncover data-driven disease phenotypes with distinct temporal progression patterns, from widely available cross-sectional patient studies. Results from imaging studies in two neurodegenerative diseases reveal subgroups and their distinct trajectories of regional neurodegeneration. In genetic frontotemporal dementia, SuStaIn identifies genotypes from imaging alone, validating its ability to identify subtypes; further the technique reveals within-genotype heterogeneity. In Alzheimer’s disease, SuStaIn uncovers three subtypes, uniquely characterising their temporal complexity. SuStaIn provides fine-grained patient stratification, which substantially enhances the ability to predict conversion between diagnostic categories over standard models that ignore subtype ( p = 7.18 × 10 −4 ) or temporal stage ( p = 3.96 × 10 −5 ). SuStaIn offers new promise for enabling disease subtype discovery and precision medicine.

Abstract Emerging adulthood, viewed through the lens of life course health development, has the potential to be a very positive developmental stage with postindustrial societies giving adolescents and emerging adults a greater opportunity for choice and exploration but also greater challenges with greater educational and social role requirements. The loss of supports and structures offered by schools, families, and child- and family-oriented health and social services means that the emerging adult must rely more on his/her own resources in a less structured environment. This increased agency in the context of less structure is occurring as the human brain is still developing higher-level capacities such as executive functioning. The person-context interactions during EA are many and complex, leading to multiple different pathways through emerging adulthood. Those with sufficient economic and adult supports as well as personal resources and maturity will be more likely to choose well and embark on a positive trajectory during EA. Those lacking these resources, or those with physical and mental health or intellectual disabilities, may struggle during this period and experience a negative trajectory in the spheres of education, vocation, relationships, and health status. The life course health science of EA requires more detailed and deeper analysis of the relationship between family, peers, and societal supports and personal internal resources in order to help promote successful developmental trajectories during EA.

Adhesive small bowel obstruction (ASBO) is a common surgical emergency, causing high morbidity and even some mortality. The adhesions causing such bowel obstructions are typically the footprints of previous abdominal surgical procedures. The present paper presents a revised version of the Bologna guidelines to evidence-based diagnosis and treatment of ASBO. The working group has added paragraphs on prevention of ASBO and special patient groups. The guideline was written under the auspices of the World Society of Emergency Surgery by the ASBO working group. A systematic literature search was performed prior to the update of the guidelines to identify relevant new papers on epidemiology, diagnosis, and treatment of ASBO. Literature was critically appraised according to an evidence-based guideline development method. Final recommendations were approved by the workgroup, taking into account the level of evidence of the conclusion. Adhesion formation might be reduced by minimally invasive surgical techniques and the use of adhesion barriers. Non-operative treatment is effective in most patients with ASBO. Contraindications for non-operative treatment include peritonitis, strangulation, and ischemia. When the adhesive etiology of obstruction is unsure, or when contraindications for non-operative management might be present, CT is the diagnostic technique of choice. The principles of non-operative treatment are nil per os, naso-gastric, or long-tube decompression, and intravenous supplementation with fluids and electrolytes. When operative treatment is required, a laparoscopic approach may be beneficial for selected cases of simple ASBO. Younger patients have a higher lifetime risk for recurrent ASBO and might therefore benefit from application of adhesion barriers as both primary and secondary prevention. This guideline presents recommendations that can be used by surgeons who treat patients with ASBO. Scientific evidence for some aspects of ASBO management is scarce, in particular aspects relating to special patient groups. Results of a randomized trial of laparoscopic versus open surgery for ASBO are awaited.

OBJECTIVE: The aim of this evidence-based report was to review pertinent randomized controlled studies that describe hemodynamic goals in acute, critically ill patients and to evaluate outcome of resuscitation therapy in association with physiologic, clinical, and therapeutic influences. METHODS: MEDLINE was the source of randomized controlled studies written in English. The inclusion criteria were acutely ill, high-risk elective surgery, trauma, and septic patients. The goals of therapy were to resuscitate to either normal or supranormal values; the latter were described as a cardiac index of >4.5 L x min(-1) x m(-2), pulmonary artery occlusion pressure of <18 mm Hg, oxygen delivery of >600 mL x min(-1) x m(-2), and oxygen consumption of >170 mL x min(-1) x m(-2). The outcome criterion was survival or death. We found 21 randomized clinical trials described in 20 articles. The studies were divided into groups based on the time that goals were implemented (i.e., "early," 8 to 12 hrs postoperatively or before organ failure, vs. "late," or after onset of organ failure) and the severity of illness, determined by the control group mortality as >20% (12 studies) or <15% (nine studies). RESULTS: In severely ill patients (control mortalities group >20%), six studies had a 23% mortality difference (p <.05) between the control and protocol groups with early optimization, but seven studies optimized after the development of organ failure did not have significantly improved mortality. Moreover, outcome was not significantly improved in less severely ill patients (control mortalities group <15%) and normal values as goals or when therapy did not improve oxygen delivery. CONCLUSION: Review of 21 randomized controlled trials with various approaches to treatment revealed statistically significant mortality reductions, with hemodynamic optimization, when patients with acute critical illness were treated early to achieve optimal goals before the development of organ failure, when there were control group mortalities of >20% and when therapy produced differences in oxygen delivery between the control and protocol groups.

Tau is a hallmark pathology of Alzheimer's disease, and animal models have suggested that tau spreads from cell to cell through neuronal connections, facilitated by β-amyloid (Aβ). We test this hypothesis in humans using an epidemic spreading model (ESM) to simulate tau spread, and compare these simulations to observed patterns measured using tau-PET in 312 individuals along Alzheimer's disease continuum. Up to 70% of the variance in the overall spatial pattern of tau can be explained by our model. Surprisingly, the ESM predicts the spatial patterns of tau irrespective of whether brain Aβ is present, but regions with greater Aβ burden show greater tau than predicted by connectivity patterns, suggesting a role of Aβ in accelerating tau spread. Altogether, our results provide evidence in humans that tau spreads through neuronal communication pathways even in normal aging, and that this process is accelerated by the presence of brain Aβ.

In a retrospective study, 58 patients with 60 tibial plafond fractures were treated by internal fixation and reviewed over an average follow-up period of 2.5 years. There were three Reudi Type I, 27 Reudi Type II, and 30 Reudi Type III fractures. Twelve fractures were open, and 60% of the fractures were the result of high-energy trauma. Results were evaluated based on a subjective and objective rating system. There were 15 good and excellent (25%), 15 fair (25%), and 30 poor results (50%). The deep infection rate in Reudi Types I and II fractures was 0%, and in Type III fractures it was 37%. The deep infection rate statistically correlated with the presence of a postoperative wound dehiscence or skin slough but not with the presence of an open fracture. Overall clinical rating correlated with the Reudi classification, quality of reduction, and the presence of a postoperative wound infection. The ankle fusion rate for Reudi Types I and II fractures was 10%, whereas that in Reudi Type III fractures was 26%. The results of this study show that operative treatment of complex intraarticular fractures of the distal tibia remain fraught with difficulty and that the complication rates and need for further reconstructive surgery remains high. If anatomic reduction without soft-tissue complications cannot be predicted preoperatively, consideration should be given to alternative types of treatment.

We present a theory for nonlinear, multidimensional plasma waves with phase velocities near the speed of light. It is appropriate for describing plasma waves excited when all electrons are expelled out from a finite region by either the space charge of a short electron beam or the radiation pressure of a short intense laser. It works very well for the first bucket before phase mixing occurs. We separate the plasma response into a cavity or blowout region void of all electrons and a sheath of electrons just beyond the cavity. This simple model permits the derivation of a single equation for the boundary of the cavity. It works particularly well for narrow electron bunches and for short lasers with spot sizes matched to the radius of the cavity. It is also used to describe the structure of both the accelerating and focusing fields in the wake.