Radiographic calibration for pubic diastasis assessment in bladder exstrophy-epispadias complex: a phantom study.

BACKGROUND: The assessment of pubic diastasis is important for the surgical planning of patients with bladder exstrophy-epispadias complex. Understanding how the diastasis changes during surgical follow-up may help predict patient morbidity. Radiography can follow diastasis but may be affected by patient and technical imaging factors including body size, imaging protocol, and equipment. Using imaging calibration and anatomic ratios may mitigate differences due to these aspects. OBJECTIVE: Use imaging phantoms to assess the effect of radiographic calibration on measurements of pubic diastasis and an internal anatomic ratio as a child grows. MATERIALS AND METHODS: Radiographic images were obtained of three different sizes of computed tomography phantoms (older child, child, and infant) using three imaging techniques that include the osseous pelvis in children. All phantoms were imaged with abdomen and pelvis techniques. The infant phantom was additionally imaged using a thoracoabdominal technique. These exposures were all repeated with systems from three manufacturers. Linear measurements were made between radiographic markers placed to simulate pubic diastasis and sacral width. A ratio was also created between these distances. Measurements with and without image calibration were made by two pediatric radiologists using rulers placed at the time of image acquisition. RESULTS: There was excellent interrater agreement for measurements, ICC >0.99. Anterior distances were more affected by magnification than posterior ones with a significant difference between uncalibrated versus calibrated anterior distances (p=0.04) and not for posterior ones (p=0.65). There was no difference between radiographic equipment manufacturers without or with calibration (p values 0.66 to 0.99). There was a significant difference in simulated pubic distance between thoracoabdominal and abdomen (p=0.04) as well as pelvic (p=0.04) techniques which resolved with calibration, each p=0.6. The ratio between the simulated pubic diastasis and sacral width differed by phantom size (all p<0.01) and imaging technique (p values 0.01 to 0.03) with or without calibration. However, the numerical differences may not be clinically significant. CONCLUSION: Image calibration results in more uniform measurements that are more accurate than uncalibrated ones across patient size, imaging techniques, and equipment. Image calibration is necessary for accurate measurement of inter-pubic distances on all projection imaging. Small differences in the pelvic ratio likely are not clinically significant, but until there is a better understanding, image calibration may be prudent.

Development of Gestational Age-Based Fetal Brain and Intracranial Volume Reference Norms Using Deep Learning.

BACKGROUND AND PURPOSE: Fetal brain MR imaging interpretations are subjective and require subspecialty expertise. We aimed to develop a deep learning algorithm for automatically measuring intracranial and brain volumes of fetal brain MRIs across gestational ages. MATERIALS AND METHODS: This retrospective study included 246 patients with singleton pregnancies at 19-38 weeks gestation. A 3D U-Net was trained to segment the intracranial contents of 2D fetal brain MRIs in the axial, coronal, and sagittal planes. An additional 3D U-Net was trained to segment the brain from the output of the first model. Models were tested on MRIs of 10 patients (28 planes) via Dice coefficients and volume comparison with manual reference segmentations. Trained U-Nets were applied to 200 additional MRIs to develop normative reference intracranial and brain volumes across gestational ages and then to 9 pathologic fetal brains. RESULTS: Fetal intracranial and brain compartments were automatically segmented in a mean of 6.8 (SD, 1.2) seconds with median Dices score of 0.95 and 0.90, respectively (interquartile ranges, 0.91-0.96/0.89-0.91) on the test set. Correlation with manual volume measurements was high (Pearson r = 0.996, P < .001). Normative samples of intracranial and brain volumes across gestational ages were developed. Eight of 9 pathologic fetal intracranial volumes were automatically predicted to be >2 SDs from this age-specific reference mean. There were no effects of fetal sex, maternal diabetes, or maternal age on intracranial or brain volumes across gestational ages. CONCLUSIONS: Deep learning techniques can quickly and accurately quantify intracranial and brain volumes on clinical fetal brain MRIs and identify abnormal volumes on the basis of a normative reference standard.

Early urodynamic findings after complete primary repair of exstrophy.

INTRODUCTION: Detrusor contraction in bladder exstrophy (BE) patients following reconstruction is poorly understood as there are few published studies assessing urodynamic findings in this population. Understanding the ability of the detrusor to contract in BE patients early after closure may be able to inform the longer-term management and potential for the development of future continence in this population. OBJECTIVE: We sought to evaluate early detrusor contraction using urodynamic studies (UDS) in children who had previously undergone complete primary repair of bladder exstrophy (CPRE). We hypothesized that a majority of children with BE would display the presence of normal detrusor contractile function after CPRE. STUDY DESIGN: A retrospective review of our prospectively collected database was performed for all patients with a diagnosis of classic BE who underwent primary CPRE between 2013 and 2017. From this cohort we identified patients with at least one post-operative UDS at 3 years of age or older who had undergone an initial CPRE. Our primary outcome was the presence of a detrusor contraction demonstrated on UDS. RESULTS: There were 50 children (31 male, 19 female) with CBE who underwent CPRE between 2013 and 2017.There were 26 (13 male, 13 female) who met inclusion criteria. Median age was 3.5 (IQR: 3.2-4.7) years at the time of UDS Sixteen of the 26 (61.5%) generated a sustained detrusor contraction generating a void, with a median peak voiding pressure of 38 cm H20 (IQR: 28-51). The median bladder capacity reached was 48 ml, which represented a median of 30% of expected bladder capacity. The median post void residual (PVR) for the entire cohort was 26 ml (IQR: 9, 47) or 51% (IQR: 20%-98%) of their actual bladder capacity, while the median PVR for those children with a sustained detrusor contraction was 18 ml (IQR: 5, 46) or 33% (IQR: 27%, 98%) of their actual bladder capacity. Intraoperative bladder width and bladder dome to bladder neck length did not correlate with the presence of voiding via a detrusor contraction (p = 0.64). DISCUSSION: We present the first study assessing early UDS finding of detrusor contraction in BE patients after CPRE. In our cohort, 61.5% of patients were able to generate a sustained detrusor contraction on UDS which is a higher percentage than has been reported in previous series. A difference in initial surgical management may account for these findings. CONCLUSION: At short term follow up, the majority of children in our cohort were able to produce sustained detrusor contractions sufficient to generate a void per urethra with a modest post void residual volume. Long-term follow-up and repeated UDS will be needed to track detrusor contractility rates, bladder capacities, compliance, post void residuals and ultimately continence rates over time.

Why are pediatric urologists unable to predict renal deterioration using urodynamics? A focused narrative review of the shortcomings of the literature.

In this focused narrative review we set out to review the current literature addressing the utilization of UDS in patients with spina bifida (SB). We specifically analyzed 6 urodynamic parameters and their roles as predictors of upper tract deterioration in pediatric SB patients. The material available did not allow a systematic analysis or the usage of metanalysis methodology, due to the predominance of small retrospective cohorts, and high heterogeneity. We identified 10 retrospective chart reviews that met our study criteria. The results of each of these papers, as well as other studies deemed relevant to the discussion, are included in our narrative review of the literature. We summarize the current literature, offer explanations for divergences in opinion, and identify future research directions and emerging solutions with a focus on machine learning.

Impact of bilateral ureteral reimplantation at the time of complete primary repair of bladder exstrophy on reflux rates, renogram abnormalities and bladder capacity.

INTRODUCTION: Bilateral ureteral reimplantation at the time of the complete primary repair of bladder exstrophy (BUR-CPRE) has been proposed and has demonstrated favorable outcomes in the past. However, the potential benefits, including prevention of vesicoureteral reflux (VUR) and renal scarring must be tempered with any risks of reimplantation, persistent VUR, and the potential for overtreatment. We aimed to determine the impact of BUR-CPRE on reflux rates, renogram findings and bladder capacity. METHODS: An IRB approved registry of children treated for bladder exstrophy epispadias complex (BEEC) during a long-term international collaboration hosted in a region with high prevalence of BEEC was queried. Children undergoing primary CPRE for bladder exstrophy (BE) were identified. Surgical procedure and outcome measures nuclear medicine dimercaptosuccinic acid (DMSA) scintigraphy scans, voiding cystourethrogram (VCUG), and urodynamic study (UDS) were assessed for presence and degree of VUR, renogram abnormalities, and bladder capacity. RESULTS: A total cohort of 147 patients with BEEC was queried; 52 children (37 males, 71%) underwent primary CPRE for BE between 2009 and 2019 at median age of 1.1 years (IQR 0.6-1.9 years) with median follow up 4.4 years (IQR 2.4-6.4 years). BUR-CPRE was performed in 22/52 (42%). After BUR-CPRE, children were less likely to have VUR (any VUR present in 9 of 20 with imaging (45%) compared to 23 of 26 with imaging (82%) in the CPRE alone group (p = 0.007)). VUR in the BUR-CPRE group tended to be unilateral and lower grade in comparison to the CPRE alone group. DMSA abnormalities were less common in the BUR-CPRE group (4/19 (21%) vs.12/27 (44%)), although the difference did not reach statistical significance (p = 0.1). At 4 years follow-up, the BUR-CPRE group had a larger bladder capacity (p = 0.016). DISCUSSION: After BUR-CPRE, children had a lower rate of VUR, and when present, VUR was more often unilateral and lower grade compared to the CPRE alone group. Fewer numbers of children in the BUR-CPRE group depicted DMSA abnormalities. No children developed obstruction after BUR-CPRE and none have undergone repeat reimplantation. We documented a larger bladder capacity at the time of maximum follow-up available (4 years)-but further data are needed to confirm this observation. CONCLUSION: BUR-CPRE decreases the incidence and severity of VUR after CPRE, but the clinical significance of this remains unclear. We are encouraged by these initial results, but since BUR-CPRE does not uniformly eliminate VUR, we continue to proceed carefully in the well selected patient.

Outcomes of externalized pyeloureteral versus internal ureteral stent in pediatric robotic-assisted laparoscopic pyeloplasty.

INTRODUCTION: After pyeloplasty, urinary drainage options include internal double-J (DJ) ureteral stents or externalized pyeloureteral (EPU) stents, which can avoid bladder symptoms and additional anesthetic exposure from stent removal. Comparative outcome studies, however, are lacking following primary pediatric robotic-assisted laparoscopic pyeloplasty (RALP). OBJECTIVE: To compare operative success, operative time, hospitalization, and postoperative complications of EPU versus DJ stents following RALP. STUDY DESIGN: Consecutive children undergoing primary RALP from 10/2013 to 9/2015 were retrospectively identified. Data collected included patient demographics, stent type and duration, postoperative complications, and operative success. To control for confounding by indication for EPU stent, propensity score weighting was used to balance baseline covariates. Weighted regression analyses compared between-group differences in study outcomes. RESULTS: At median follow-up of 12.3 months, 44 and 17 patients underwent DJ and EPU stenting, respectively. At baseline, DJ stent patients were older than EPU stent patients (median 7.7 vs 1.2 years, P = 0.01) and were less likely to be on postoperative antibiotic prophylaxis (25 vs 76%, P < 0.001). After weighting, these differences disappeared. All EPU stents were removed in the outpatient clinic; all DJ stents were removed under anesthesia. On weighted regression analyses (Summary Fig.), EPU stents had no different associations than DJ stents with operative success (95 vs 94%, between-group difference 1%, 95% CI -11, 13; P = 0.86), complications, or operative time, but did have 0.6 of a day more hospitalization (95% CI 0.04, 1.2; P = 0.04). DISCUSSION: Patients receiving EPU stents were different at baseline from those receiving DJ stents. After propensity score weighting balanced these covariates, EPU stents were associated with similar operative success, complications, and operative time to DJ stents. Further study is warranted in larger prospective cohorts. CONCLUSION: Use of EPU stents provided a viable alternative, particularly in younger patients, to DJ stenting with comparable success and complications, while avoiding the need for an additional anesthetic.

Back to the future: The Cecil-Culp technique for salvage penile reconstructive procedures.

INTRODUCTION: Re-operative penile reconstruction is challenging and requires tension-free skin closure. The repair popularized by Cecil and Culp in the 1940s, using the scrotum to provide a temporary vascularized bed for complex hypospadias repairs, fell out of favor due to temporal trends towards single-stage repairs and concern for utilizing hair-bearing skin on the penile shaft. OBJECTIVE: It was hypothesized that a modified Cecil-Culp (CC) concept of penile scrotalization, leaving the penis attached to the scrotum for 1 year rather than 6 weeks as originally described, improves outcomes with this reconstruction for ventral skin deficiency or poor vascular support. METHODS: Institutional Review Board-approved registries were reviewed to identify patients who underwent a CC repair during 1987-2016 at two institutions. Cecil-Culp technique was utilized in multi-stage hypospadias complication repairs or for insufficient ventral penile shaft skin coverage. Anatomic abnormality, number and type of prior surgeries, and complications before and after CC were recorded. RESULTS: Thirty-nine patients underwent CC: 23 failed hypospadias repairs, three hypospadias after bladder exstrophy, 10 penile curvature following circumcision, and three with skin loss from trauma. Mean age at CC was 61.8 months (hypospadias), and 59.8 months (non-hypospadias). Hypospadias patients underwent a mean of 3.6 surgeries (range 1-9) prior to CC. Four of the 39 patients (10.3%) had perioperative complications after CC, including scrotal abscess, skin infections, and difficulty removing the urethral stent. Eight of 37 (21.6%) patients had longer-term complications related to their hypospadias repair, including fistulae, diverticula, dehiscence, and stricture. Mean time from CC placement to release was 345 and 473 days for hypospadias and non-hypospadias cases, respectively. There was no apparent scrotal skin transferred to the penile shaft at the final take-down. Mean follow-up was 22.3 months. DISCUSSION: Embedding the penis into the scrotum for added vascularity and ventral skin coverage has been used effectively in cases of the most tenacious fistulas and for significant skin loss and trauma. Limitations of this study were its retrospective approach at two institutions over an extended period of time by multiple surgeons, so patient selection and procedure may have varied. CONCLUSIONS: Modification of CC repair by delaying 9-12 months before CC take-down enhanced the benefits of a robust vascular bed for wound healing, and helped to avoid transfer of hair-bearing scrotal skin to the penile shaft. The CC technique is an important tool for penile reconstructive surgery of complex hypospadias repairs with inadequate skin, and for traumatic injuries.

Tunica vaginalis flap for salvaging testicular torsion: A matched cohort analysis.

INTRODUCTION: In testicular torsion, ischemia time from pain onset impacts testicular salvage. A tunica albuginea fasciotomy to relieve compartment pressure followed by a tunica vaginalis flap (TVF) may enhance salvage. OBJECTIVE: To define the optimal window of ischemia time during which TVF may be most beneficial to avoid orchiectomy. STUDY DESIGN: A retrospective cohort study of males presenting with testicular torsion at a single tertiary-care institution from January, 2003 to March, 2017. Ischemia time was defined as duration of pain from onset to surgery. Because TVF would be an option to orchiectomy, and it was found that ischemia time was longer in testicles that underwent orchiectomy, matching was performed. Cases of torsion treated with TVF were matched 1:1 with cases treated with orchiectomy on age at surgery, and ischemia time. Outcomes included postoperative viability, defined as palpable testicular tissue with normal consistency, and atrophy, defined as palpable decrease in size relative to contralateral testicle. Sensitivity analyses were performed restricting to the subgroups with postoperative ultrasound, >6 months' follow-up, and additionally matching for degrees of twist. RESULTS: A total of 182 patients met eligibility criteria, of whom 49, 36, and 97 underwent orchiectomy, TVF, and septopexy alone, respectively. Median follow-up was 2.7 months; 26% of patients had postoperative ultrasound (61% of TVF group). In the orchiectomy, TVF, and septopexy groups, respectively, median ischemia times were 51, 11, and 8 h, postoperative viability rates were 0, 86, and 95%, and postoperative atrophy rates were 0, 68, and 24%. After matching, 32 patients with TVF were matched to 32 patients who underwent orchiectomy. In the TVF group, postoperative viability occurred in 95% (19/20) vs 67% (8/12) of patients with ischemia times ≤24 and >24 h, respectively. Atrophy occurred in 67% (12/18) vs 83% (10/12) of these same respective patients. Sensitivity analysis by ultrasound and longer follow-up found similar viability results, although atrophy rates were higher. Additional matching for degrees of twist showed lower viability and higher atrophy rates for increasing ischemia times. DISCUSSION: Patients who presented with testicular torsion with ischemia times ≤24 h and who were being considered for orchiectomy may have benefitted most from TVF, albeit at high risk of atrophy. However, for ischemia times >24 h, TVF may still have preserved testicular viability in two-thirds of cases. A limitation was short follow-up. CONCLUSION: A TVF was a valid alternative to orchiectomy for torsed testicles, albeit with high testicular atrophy rates.

Genitourinary involvement and management in children with Stevens-Johnson syndrome and toxic epidermal necrolysis.

BACKGROUND: Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are devastating hypersensitivity disorders that cause epidermal cell death and can affect all epidermal surfaces, including the urethra, vagina, labial and scrotal skin. Despite the well-described ocular and orofacial manifestations of SJS/TEN, there is a paucity of reports on the genitourinary (GU) symptoms and their management. Specifically, consulting services often ask the pediatric urology team if it is safe to place a urethral catheter, but there is no data in the literature to help guide management. The present study sought to review all pediatric cases of SJS/TEN in a tertiary care hospital to determine the incidence and optimal management of GU manifestations, including the use of urethral catheters. METHODS: With IRB approval, cases of SJS and TEN that were managed as an inpatient between January 2008 and June 2015 were retrospectively reviewed in order to identify the extent of GU involvement/manifestations, the treatment provided, use of urethral catheterization and long-term follow-up or complications. RESULTS: Thirty-one patients (15 female, 16 male; age range 2-18 years) presented with SJS or TEN over the study period. Etiologies for SJS/TEN included mycoplasma infection (48%) and medications (45%). Incidences of GU manifestations at presentation and their management are shown in Summary Table. Overall, 74% of patients had genital involvement of skin lesions. In 12 cases (39%), urology consultation was obtained. Twenty patients (61%) complained of dysuria and one child had gross hematuria in the setting of meatal lesion. Petroleum jelly was used in the majority of patients. A urethral catheter was placed in eight patients (25.8%, four female, four male) with a range of duration of 7-23 days. No patient developed hematuria or any other complications (i.e. strictures or urinary symptoms) after catheter removal. One boy required lysis of penile adhesions in the short-term. One of each gender developed penile and labial adhesions on long-term follow-up that self-resolved. CONCLUSIONS: GU involvement in SJS/TEN occurred in almost three-quarters of patients and was managed conservatively like other skin/mucosal manifestations. Long-term sequelae were rare and urethral catheterization appeared to be safe, without any short-term or long-term complications.

How do they get here: Does the method of transportation impact salvage for patients with testicular torsion?

INTRODUCTION: A growing number of patients are arriving at our tertiary care center for evaluation of possible testicular torsion using ambulance or helicopter transport. In many cases the parents arrive by car before the patient arrives. Are these advanced methods of medical transport worth the expense and risk in the case of suspected testicular torsion? OBJECTIVE: We evaluated the total number of patients presenting to our emergency room for suspected testicular torsion to see if the means of transport affected testicular survival. STUDY DESIGN: Retrospective. RESULTS: As shown below in the table, the means of transport did not impact on testicular salvage. DISCUSSION: It is understandable that many patients with scrotal pain seek treatment closer to home because of their pediatrician's recommendation and/or family preference. However once evaluated many patients are transferred because of a lack of urologists willing to evaluate and treat the pediatric patients in community settings or because of a lack of anesthesia support. These patients are often transported by ambulance or helicopter. Our data would suggest that there is no improvement in the testicular salvage rate seen with these more advanced means of medical transportation compared with transfer by private car even when we restrict the analysis to patients traveling from over 40 miles away. We suspect that important time is lost while waiting to make such transfer arrangements. Furthermore transfer by ambulance or helicopter is more expensive and these costs are often passed on to families. Transfer by helicopter is also riskier. While an argument can be made in favor of medical transport over long distances or long driving times, this data suggests that many of these transfers could be accomplished by car with no effect on testicular salvage rates. CONCLUSION: The rate of testicular salvage was not affected by the means of transport to our tertiary facility. Only 4 patients would have required advanced of medical transport if this were limited to those facilities over 100 miles or 1.5 hours driving time away. This would achieve a substantial cost savings with no measurable change in outcome.

Pediatric calyceal diverticulum treatment: An experience with endoscopic and laparoscopic approaches.

INTRODUCTION: The symptomatic calyceal diverticulum is a rare event in the pediatric population. In adults, surgical options include ureteroscopy, percutaneous ablation, and laparoscopic decortication but there is a lack of experience in the literature with these techniques. OBJECTIVE: We present our experience with both the ureteroscopic and laparoscopic approach to treating the pediatric calyceal diverticulum. STUDY DESIGN: We performed a retrospective case series looking at patients who underwent treatment for calyceal diverticulum at our institution from January 2009 to May 2014. We reviewed patient demographics, indications for intervention, radiographic appearance, type of intervention, and perioperative outcomes. Ureteroscopic approach included dilation of infundibulum and ablation of diverticular cavity. Laparoscopic approach included ablation of the diverticulum with argon diathermy with or without surgical closure of the ostium. RESULTS: There were 13 patients who underwent 15 procedures for symptomatic calyceal diverticulum (Table). Median age was 11 years. Indications for intervention were: pain and increasing size of diverticulum (8/15, 55%), hematuria (3/15, 20%), UTI (3/15, 20%), and calculi (1/15, 5%). 11/15 (73%) procedures were managed endoscopically and 4/15 (27%) were managed with laparoscopic decortication. Ureteral stent was left in all patients for a mean duration of 51 days (15-120 days). Follow up imaging at median of 2.1 years (0.5-4 years) revealed an initial success rate of 85% (11/13 patients). Two patients failed initial intervention (persistent pain/increasing size) necessitating successful secondary minimally invasive procedures. There were 2 (13%) complications: a perinephric hematoma post endoscopic ablation which resolved spontaneously and a deep venous thrombosis in a patient with a coagulation disorder in the laparoscopic group. DISCUSSION: Limitations of our study include its retrospective design, lack of standardization of the treatment approach amongst the four treating surgeons, and the small number of patients requiring intervention for this relatively rare diagnosis. Our study is the largest to date in the pediatric population and is the first to report outcomes with ureteroscopic management of the calyceal diverticulum. CONCLUSIONS: We found that the pediatric calyceal diverticulum can be successfully treated in a minimally invasive manner. The endoscopic approach should be the first line option for patients with small, endophytic diverticula, particularly those located in the upper and mid pole. The laparoscopic approach is more invasive but should be considered for large diverticula that are exophytic with thin overlying parenchyma.

PCR-based microsatellite analysis for differentiation and genetic monitoring of nine inbred SENCAR mouse strains.

Sixteen DNA microsatellites or simple sequence length polymorphisms (SSLPs), generated by polymerase chain reaction (PCR) were selected for use in the genetic quality control of the nine inbred SENCAR strains currently available. The SENCAR strains constitute a powerful tool for mechanistic studies of multi-stage skin carcinogenesis, as well as for studies to understand the underlying genetic basis of resistance to tumour promotion and progression. SSLP analysis is a fast and economical way for detecting genetic contamination (unexpected outcrosses) among these closely-related albino strains, where standard immunological and biochemical markers have been shown to be insufficient.

See the light: Project Spectrum solves some of healthcare's most challenging IT problems.

UNLABELLED: BJC Health System, St. Louis. PROBLEM: Changes in healthcare, including the growth of managed care forced administrators at BJC to find new ways to address patients' needs across the entire continuum of care. To meet this challenge, disparate legacy information systems had to begin communicating. SOLUTION: BJC officials turned to IBM, along with Kodak, Southwestern Bell and Motorola, for the creation of Project Spectrum--a system that reaches beyond the boundaries of this acute care facility. RESULTS: Project Spectrum accomplishes three goals: allows access to clinical data from anywhere in the health system; is user friendly and fast; and provides the tools for better and efficient care. KEYS TO SUCCESS: "There is no quick fix. True integration means a long-term, institutional commitment to information system objectives."

Hospital saves with bedside point-of-care system.

Do bedside and point-of-care systems actually deliver on their promise of reducing operating expenses while helping improve the overall quality of healthcare? And how does a healthcare facility quantify associated "productivity" improvements to prove cost savings? These are two critical issues that healthcare providers face in implementing a bedside or point-of-care (POC) system. Barnes Hospital, St. Louis, is a 1,000 bed member facility of the Barnes-Jewish Inc./Christian Health Services integrated health system. Barnes Hospital has indeed seen significant cost savings as a result of a POC project.

The CIO's position in today's emerging health care system: lessons learned.

The integrated delivery network is a new concept. Using information technology as a rallying point has allowed people to come together in a non-threatening way. They discuss new ideas and possibilities for improving the performance of their individual institution and thus, the entire Network. How quickly and how well business adapts to this new model will dictate long-term viability in the marketplace. Technology will not be the limiting factor to success in this new endeavor. It will be a facilitator that can help the organizational transition from single institutions to an IDN. The challenge is in managing how well personnel accept this change and seek ways to work together in this new endeavor. The ability to perform competently at these new levels comes from the ability to perform as a senior executive, acting in partnership and peer relationships as a facilitator and leader. To manage the change required in these new organizations, there must be common vision, the creation of new roles, agreed upon priorities, flexibility, and standardization when necessary. While there is not one right solution, leadership and shared vision and the ability to deliver are key success factors.

High-resolution Y chromosome haplotypes of Israeli and Palestinian Arabs reveal geographic substructure and substantial overlap with haplotypes of Jews.

High-resolution Y chromosome haplotype analysis was performed in 143 paternally unrelated Israeli and Palestinian Moslem Arabs (I&P Arabs) by screening for 11 binary polymorphisms and six microsatellite loci. Two frequent haplotypes were found among the 83 detected: the modal haplotype of the I&P Arabs (approximately 14%) was spread throughout the region, while its one-step microsatellite neighbor, the modal haplotype of the Galilee sample (approximately 8%), was mainly restricted to the north. Geographic substructuring within the Arabs was observed in the highlands of Samaria and Judea. Y chromosome variation in the I&P Arabs was compared to that of Ashkenazi and Sephardic Jews, and to that of North Welsh individuals. At the haplogroup level, defined by the binary polymorphisms only, the Y chromosome distribution in Arabs and Jews was similar but not identical. At the haplotype level, determined by both binary and microsatellite markers, a more detailed pattern was observed. Single-step microsatellite networks of Arab and Jewish haplotypes revealed a common pool for a large portion of Y chromosomes, suggesting a relatively recent common ancestry. The two modal haplotypes in the I&P Arabs were closely related to the most frequent haplotype of Jews (the Cohen modal haplotype). However, the I&P Arab clade that includes the two Arab modal haplotypes (and makes up 32% of Arab chromosomes) is found at only very low frequency among Jews, reflecting divergence and/or admixture from other populations.

Genetic evidence for different male and female roles during cultural transitions in the British Isles.

Human history is punctuated by periods of rapid cultural change. Although archeologists have developed a range of models to describe cultural transitions, in most real examples we do not know whether the processes involved the movement of people or the movement of culture only. With a series of relatively well defined cultural transitions, the British Isles present an ideal opportunity to assess the demographic context of cultural change. Important transitions after the first Paleolithic settlements include the Neolithic, the development of Iron Age cultures, and various historical invasions from continental Europe. Here we show that patterns of Y-chromosome variation indicate that the Neolithic and Iron Age transitions in the British Isles occurred without large-scale male movements. The more recent invasions from Scandinavia, on the other hand, appear to have left a significant paternal genetic legacy. In contrast, patterns of mtDNA and X-chromosome variation indicate that one or more of these pre-Anglo-Saxon cultural revolutions had a major effect on the maternal genetic heritage of the British Isles.

Y chromosomes traveling south: the cohen modal haplotype and the origins of the Lemba--the "Black Jews of Southern Africa".

The Lemba are a traditionally endogamous group speaking a variety of Bantu languages who live in a number of locations in southern Africa. They claim descent from Jews who came to Africa from "Sena." "Sena" is variously identified by them as Sanaa in Yemen, Judea, Egypt, or Ethiopia. A previous study using Y-chromosome markers suggested both a Bantu and a Semitic contribution to the Lemba gene pool, a suggestion that is not inconsistent with Lemba oral tradition. To provide a more detailed picture of the Lemba paternal genetic heritage, we analyzed 399 Y chromosomes for six microsatellites and six biallelic markers in six populations (Lemba, Bantu, Yemeni-Hadramaut, Yemeni-Sena, Sephardic Jews, and Ashkenazic Jews). The high resolution afforded by the markers shows that Lemba Y chromosomes are clearly divided into Semitic and Bantu clades. Interestingly, one of the Lemba clans carries, at a very high frequency, a particular Y-chromosome type termed the "Cohen modal haplotype," which is known to be characteristic of the paternally inherited Jewish priesthood and is thought, more generally, to be a potential signature haplotype of Judaic origin. The Bantu Y-chromosome samples are predominantly (>80%) YAP+ and include a modal haplotype at high frequency. Assuming a rapid expansion of the eastern Bantu, we used variation in microsatellite alleles in YAP+ sY81-G Bantu Y chromosomes to calculate a rough date, 3,000-5,000 years before the present, for the start of their expansion.