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This case series evaluated use of injectable platelet rich fibrin (termed i-PRF+) for the treatment of female pattern hair loss (FPHL). Eleven individuals underwent 3-monthly intradermal injections of i-PRF+ using a mesotherapy gun. The mean number of hair follicles containing hairs per unit area improved at 3- and 6-months follow-up (p <.001), and all participants had a negative hair pull test. Hair volume and thickness, and patient-reported outcome scores also improved at follow-up (p <.001). Adverse effects were minor and self-limited. A series of three i-PRF+ injection sessions were effective for the treatment of FPHL, as shown by improved hair analysis parameters and patient self-assessment scores. [ABSTRACT FROM AUTHOR]

Background: Cosmeceutical preparations containing growth factors (GFs) are widely used for facial rejuvenation. Objective: We performed a systematic review to assess the evidence regarding their safety and effectiveness for facial rejuvenation. Methods: Electronic databases (Cochrane Library, EMBASE, MEDLINE, and Scopus) were searched from 2000 to October 2022 for prospective trials and case series assessing topical GF preparations for facial rejuvenation in 10 or more participants. Results: Thirty‐three studies, including 9 randomized controlled trials (RCTs) and 24 uncontrolled case series, representing 1180 participants receiving 23 different topical preparations containing GFs met the inclusion criteria and were included. Of the 33 studies, nine used a placebo or active control. The GF preparations were applied twice daily in all except two studies, with a mean treatment duration of 3 months. Based on the investigator's assessment, preparations containing GFs induce a modest improvement in skin texture (median < 50%), fine lines/wrinkles (median < 35%), and overall facial appearance (median < 20%) versus baseline. Participant‐assessed improvement was generally higher than investigator‐assessed response. Three comparative RCTs showed no statistically significant differences between treatments. Studies were limited by heterogeneity with regard to the source and number of GFs used in the preparations, information about additional ingredients, and lack of standardization in the outcome measures. The preparations were associated with a low risk of adverse events. The persistence of the clinical improvements beyond 6 months is not known. Conclusions: Administration of topical preparations containing GFs appears to be effective for facial skin rejuvenation, as demonstrated by the investigator‐ and participant‐reported outcome measures. [ABSTRACT FROM AUTHOR]

Background: Cosmeceutical products are an important therapeutic option for facial rejuvenation. Of these, topical application of growth factors has been shown to increase dermal collagen synthesis, improve skin texture, and reduce fine lines and wrinkles. Limited data exist for the use of growth factors in combination with microneedling. Objective: This prospective, single‐center, uncontrolled study evaluated the efficacy of topical growth factor treatment in conjunction with transdermal delivery of growth factors via home‐based microneedling for facial skin rejuvenation. Patients/Methods: Eleven healthy female individuals aged 33–61 years, with mild‐moderate facial wrinkling were included in the study. Over 3 months, participants received twice‐daily application of a topical recombinant human growth factor preparation (SkinGenuity® Regenerative and Reparative Serums) along with twice‐weekly transdermal delivery of growth factors using a home‐based microneedling (0.2 mm) device. Objective skin analysis (VISIA®) and a subjective patient‐reported outcome (FACE‐Q®) assessment measuring satisfaction with appearance were performed at baseline and after 3 months. Results: Objective skin analysis showed a significant improvement in skin texture (17.6%, p < 0.001), wrinkles (17.3%, p < 0.001), red areas (12.4%, p =0.004), and brown spots (6.0%, p =0.03) at 3 months follow‐up. FACE‐Q scales showed a significant improvement from baseline, including satisfaction with skin, facial appearance, nasolabial folds, cheeks, and lower face/jawline (all p ≤ 0.02). Numerical improvement in adverse effects related to skin was also observed (p = 0.07). No serious adverse effects were reported. Conclusions: Three months of twice‐daily topical growth factor treatment in conjunction with transdermal delivery of growth factors via microneedling improved skin analysis parameters and participant‐reported outcome measures, indicative of facial skin rejuvenation. [ABSTRACT FROM AUTHOR]

Background: Various injectable autologous platelet aggregate preparations have been developed and used for facial rejuvenation. Limited evidence exists for the use of these for augmentation of the lip. Objectives: This prospective, uncontrolled, single‐center study evaluated the qualitative and quantitative effects of an injectable platelet‐rich fibrin preparation (known as i‐PRF+) for lip augmentation. Patients/methods: PRF® PROCESS system technology was used to prepare i‐PRF+ supernatant. Ten healthy females were included in the study and received a single intradermal injection of i‐PRF+ in the upper and lower lips (5 ml in each quadrant, total ~2 ml). Participants were followed for 3 months post‐procedure. The efficacy of the procedure was assessed qualitatively by a subjective patient‐reported outcome (FACE‐Q) assessment and quantitatively by objective 3D skin surface volume analysis (ProFace®) at baseline and after 3 months. Results: FACE‐Q scales that measure satisfaction with skin and lip showed a statistically significant improvement from baseline (p = 0.04 and p = 0.02, respectively). Satisfaction with lip lines showed a numerical improvement with mean total scores for adverse effect scales related to the skin and lips reduced at 2 weeks post‐procedure (p = 0.03 and p = 0.13, respectively). Overall lip volume at 3‐month follow‐up was unchanged (p = 0.11). The treatment was well tolerated with only minor adverse effects. Conclusions: A single session of i‐PRF+ injections resulted in significant lip rejuvenation at 3‐month follow‐up, shown by improved patient‐reported outcome measure. No significant change in lip volume was observed. [ABSTRACT FROM AUTHOR]

Background: Autologous platelet‐derived preparations have been used in many surgical fields to improve healing outcomes, with benefits reported in several aesthetic indications. Aims: This single‐center, prospective, uncontrolled study evaluated the efficacy of injectable platelet‐rich fibrin (i‐PRF) for facial skin rejuvenation using an objective skin analysis system and validated patient‐reported outcome measures. Patients/Methods: PRF® PROCESS system technology was used to prepare i‐PRP. Eleven healthy female individuals were included in the study and over 3‐months received monthly intradermal injections of i‐PRF in 3 facial regions: malar areas (1 mL each side), nasolabial fold (0.5 mL each side), and upper lip skin above the vermilion border (1 mL). The efficacy of the procedures was assessed by objective skin analysis (VISIA®) and a subjective patient‐reported outcome (FACE‐Q) assessment at baseline and after 3 months. Results: A significant improvement in skin surface spots (P =.01) and pores (P =.03) was seen at 3‐months follow‐up. Other variables, such as skin texture, wrinkles, ultraviolet spots, and porphyrins, showed a numerical improvement. FACE‐Q scales that measure satisfaction with appearance all showed a significant improvement from baseline, including satisfaction with skin (P =.002), satisfaction with facial appearance (P =.025), satisfaction with cheeks (P =.001), satisfaction with lower face and jawline (P =.002), and satisfaction with lips (P =.04). No major adverse effects were reported. Conclusions: A series of three i‐PRF injections resulted in significant rejuvenation of the face skin at 3‐month follow‐up, as shown by improved skin analysis parameters and patient self‐assessment scores. [ABSTRACT FROM AUTHOR]

The aim of this study was to prospectively evaluate the diagnostic performance of strain elastography for the assessment of liver fibrosis in patients with chronic liver disease using Ishak (0–6) histology stage as a reference standard. Ninety-eight consecutive patients with suspected chronic liver disease scheduled for liver biopsy (n = 78) or histologically confirmed cirrhosis (n = 20) were enrolled. Liver fibrosis Index (LF Index) calculated by strain elastography, liver stiffness by transient elastography and serum fibrosis markers (aspartate aminotransferase-to-platelet ratio index and King's Score) were measured. Spearman's correlation coefficient between the LF Index, liver stiffness, serum fibrosis markers and fibrosis stage were calculated and compared using areas under the receiver-operating characteristics (AUROCs) curves. Among 73 patients who underwent strain elastography, there was weak correlation between fibrosis stage and the LF Index (Spearman's: ρ = 0.385 for Ishak score; P = 0.001). Among 52 patients who underwent strain elastography and transient elastography, the AUROC values using LF Index, transient elastography, aspartate aminotransferase-to-platelet ratio index and King's Score for diagnosing significant fibrosis (Ishak score ≥ 3) were 0.79, 0.87, 0.86 and 0.85, respectively (P < 0.0001) and for diagnosing severe fibrosis/cirrhosis (Ishak score ≥ 5) were 0.83, 0.94, 0.92 and 0.92, respectively (P < 0.0001). When comparing the diagnostic performance using LF Index, transient elastography, aspartate aminotransferase-to-platelet ratio index and King's Score, transient elastography shows a significantly higher AUROC value than LF Index in detecting severe fibrosis (P = 0.0149). The diagnostic performance of LF Index calculated by strain elastography was not statistically significantly different to the other noninvasive tests for the assessment of significant liver fibrosis but inferior to transient elastography for the assessment of severe fibrosis/cirrhosis. [ABSTRACT FROM AUTHOR]

Acute myeloid leukemia (AML) is an aggressive hematological malignancy that is one of the more common pediatric malignancies in addition to occurring with high incidence in the aging population. Unfortunately, these patient groups are quite sensitive to toxicity from chemotherapy. Northern Labrador tea, or Rhododendron tomentosum Harmaja (a.k.a. Ledum palustre subsp. decumbens) or "tundra tea," is a noteworthy medicinal plant used by indigenous peoples in Alaska, Canada, and Greenland to treat a diversity of ailments. However, laboratory investigations of Northern Labrador tea, and other Labrador tea family members, as botanical sources for anticancer compounds have been limited. Utilizing an AML cell line in both in vitro and in vivo studies, as well as in vitro studies using primary human AML patient samples, this study demonstrated for the first time that Northern Labrador tea extracts can exert anti-AML activity and that this may be attributed to ursolic acid as a constituent component. Therefore, this medicinal herb holds the potential to serve as a source for further drug discovery efforts to isolate novel anti-AML compounds. [ABSTRACT FROM AUTHOR]

Objectives Two-dimensional shear wave elastography (2D-SWE) imaging for the noninvasive assessment of tissue stiffness was assessed for reproducibility in healthy volunteers in quantifying liver elasticity, compared with an established point shear wave elastography (p-SWE) technique also known as virtual touch quantification (VTQ) (SIEMENS). Methods Eleven healthy volunteers were examined by four experienced operators on two occasions, separated by two weeks (sessions A and B). Ten 2D-SWE using LOGIQ E9 and p-SWE measurements using VTQ (in meters per second) were consecutively taken from deep portions of liver segments 5 or 6 away from vascular structures, using standard techniques. Inter- and intra-observer agreement was assessed by intraclass coefficient (ICC). Results A total of 880 2D-SWE and p-SWE velocities were recorded. Mean values from the four operators ranged between 1.188 and 1.196 m/s for 2D-SWE and 1.170 to 1.207 m/s for p-SWE. Interobserver reproducibility was good for both sessions with ICCs of 0.88 and 0.93 (2D-SWE) and 0.87 and 0.93 (p-SWE). The overall intra-operator reproducibility between sessions A and B was good for both p-SWE and 2D-SWE with ICC of 0.87 and 0.83, respectively. For inter- and intra-observer variability, the ICC was more than or equal to 0.71, indicating that the results were reliable. There was a strong and significant correlation between the 2D-SWE and p-SWE measurements ( r = 0.87, P = .0006), but their velocities did not agree equally across different velocities. Conclusions Two-dimensional SWE using LOGIQ E9 is a reliable and reproducible method for measuring elasticity in healthy volunteers and has a similar degree of reliability as p-SWE using VTQ, but absolute measurements from the two techniques should not be used interchangeably. [ABSTRACT FROM AUTHOR]

Aims Various definitions of major bleeding have been used to evaluate safety in randomized controlled trials of antiplatelet therapy. We compared the definitions and rates of major bleeding in phase III randomized controlled trials of oral P2Y12 inhibitors in the management of patients with acute coronary syndromes (ACS). Methods and results Electronic searches identified six phase III randomized controlled oral P2Y12 inhibitor trials published between 2001 and 2010 involving 119 020 patients with ACS. The trials compared clopidogrel standard-dose (300-mg loading dose, 75-mg daily thereafter) vs. placebo (CURE, CLARITY-TIMI 28, COMMIT), clopidogrel standard-dose vs. prasugrel (TRITON-TIMI 38) or ticagrelor (PLATO) and clopidogrel standard-dose vs. clopidogrel double-dose (600-mg loading dose, 150-mg daily for 6-days, 75-mg daily thereafter) (CURRENT-OASIS 7). Using the trial definition, major bleeding rates in patients treated with standard-dose clopidogrel ranged from 0.6% in COMMIT to 11.2% in PLATO. The contrast in bleeding rates of standard-dose clopidogrel among the trials was attenuated when using the thrombolysis in myocardial infarction (TIMI) definition for major bleeding (range 1.1–7.7%) and bleeding rates in all the trials were less than 2% when comparing 30 day rates of non-coronary artery bypass graft surgery-related TIMI major bleeding (range 0.3–1.9%). Conclusion Differences in major bleeding rates between trials of P2Y12 inhibitors in patients with ACS are minimized after standardization of bleeding definitions, timing of reporting of bleeding outcomes, and procedure rates. Interpretation of the risk of bleeding associated with different P2Y12 inhibitors would be facilitated by a consistent approach to the definition and reporting of bleeding. [ABSTRACT FROM PUBLISHER]

In this paper, we take a concrete step towards materializing our long-term goal of providing a fully automatic end-to-end tuning infrastructure for arbitrary program components and full applications. We describe a general-purpose offline auto-tuning framework and apply it to an application benchmark, SMG2000, a semi-coarsening multigrid on structured grids. We show that the proposed system first extracts computationally intensive loop nests into separate executable functions, a code transformation called outlining. The outlined loop nests are then tuned by the framework and subsequently integrated back into the application. Each loop nest is optimized through a series of composable code transformations, with the transformations parameterized by unbound optimization parameters that are bound during the tuning process. The values for these parameters are selected using a search-based auto-tuner, which performs a parallel heuristic search for the best-performing optimized variants of the outlined loop nests. We show that our system pinpoints a code variant that performs 2.37 times faster than the original loop nest. When the full application is run using the code variant found by the system, the application’s performance improves by 27%. [ABSTRACT FROM AUTHOR]

The last decade has seen the evaluation of several new oral anticoagulants that directly target thrombin or activated factor X (FXa). All demonstrate a rapid onset of action, a low potential for food and drug interactions, and a predictable anticoagulant effect that obviates the need for routine coagulation monitoring. Those agents at the most advanced stages of clinical development are a direct thrombin inhibitor, dabigatran, and direct FXa inhibitors, rivaroxaban and apixaban. Dabigatran and rivaroxaban are approved in more than 70 countries for prevention of venous thromboembolism in patients undergoing elective hip or knee arthroplasty, and apixaban is being considered for approval by regulatory agencies for this indication. Dabigatran was shown in a large phase III trial to be more effective and safer than warfarin for the prevention of stroke or systemic embolism in patients with atrial fibrillation and has recently been approved for this indication. Edoxaban, an oral FXa inhibitor, is also being evaluated in phase III clinical trials. This review summarizes the pharmacology, clinical trial results, and future role of the new oral anticoagulants in clinical practice. [ABSTRACT FROM AUTHOR]

For the past five decades, there has been little progress in the development of oral anticoagulants, with the choices being limited to the vitamin K antagonists (VKAs). The situation is changing with the development of orally active small molecules that directly target thrombin or activated factor X (FXa). The two agents in the most advanced stages of development are dabigatran etexilate and rivaroxaban, which inhibit thrombin and FXa, respectively. Both are approved in the EU and Canada for venous thromboprophylaxis in patients undergoing elective hip- or knee-replacement surgery. Other agents in the early stages of development include several FXa inhibitors (apixaban, DU 176b, LY 517717, YM 150, betrixaban, eribaxaban [PD 0348292] and TAK 442) and one thrombin inhibitor (AZD 0837). With a predictable anticoagulant response and low potential for drug-drug interactions, these new agents can be given in fixed doses without coagulation monitoring. This renders them more convenient than VKAs. While the anticoagulant effect of the new thrombin and FXa inhibitors is similar, differences in the pharmacokinetic and pharmacodynamic parameters may influence their use in clinical practice. Here, we compare the pharmacokinetic and pharmacodynamic features of these new oral agents. [ABSTRACT FROM AUTHOR]

Current anticoagulant provision is dominated by parenteral heparin and oral warfarin, which act by inhibiting several steps of the coagulation pathway indirectly. Recent research efforts have focused on the identification of small molecule inhibitors of the coagulation enzymes as novel therapies for thrombotic disorders. There has been particular success in developing nonpeptidic, orally available, small molecules to directly inhibit the key proteases, factor IIa and factor Xa. Of the new oral anticoagulants in development, the two agents in the most advanced stage are dabigatran etexilate (BIBR 1048) and rivaroxaban (BAY 59-7939), which inhibit factor IIa and factor Xa, respectively. Other agents in the early stages of development include several Xa inhibitors (LY-517717, YM150, DU-176b and apixaban [BMS-562247]), a factor IXa inhibitor (TTP889), and an orally active glycosaminoglycan enhancer (odiparcil [SB-424323]), which indirectly enhances thrombin inhibition via heparin cofactor II. Results have been reported from important, phase II dose-finding studies, and a number of registration-track phase III studies have been initiated, reflecting the drive towards potentially more effective, but primarily safer and more convenient therapies for the prevention and treatment of venous and arterial thrombosis. Indeed, two unmet needs for anticoagulation that can be easily identified are safety and ease of use. Safety relates primarily to the incidence of major bleeding and this remains the key concern of orthopaedic surgeons, over and above any efficacy advantage, and convenience of use, which centres on oral administration replacing the need for injections. The clinical development of these new anticoagulants is following the well tested strategy of dose-ranging and registration studies in major orthopaedic surgery, prior to development in arterial indications. There are a number of subtle issues, including the timing of the first perioperative dose, duration of prophylactic treatment and definition/assessment of study endpoints that can influence study outcome and require careful consideration when evaluating study results with new agents and in the comparison with established agents, and which are considered in this review. It is anticipated that over the next 3 years, at least one of these agents will be successfully licensed for the prevention of venous thromboembolism after major orthopaedic surgery, which will act as a springboard for the gradual replacement of current anticoagulants. [ABSTRACT FROM AUTHOR]

The article presents a study on the potentiality of factor V Leiden (FVL) and prothrombin to cause venous thromboembolism (VTE). The study was assessed according to three variables, the patient, design and follow-ups. The study revealed that both FVL and prothrombin are identified to be high predisposing factor to VTE.

Sophisticated parallel languages are difficult to develop; most parallel distributed memory scientific applications are developed using a serial language, expressing parallelism through third party libraries (e.g. MPI). As a result, frameworks and libraries are often used to encapsulate significant complexities. We define a novel approach to optimize the use of libraries within applications. The resulting tool, named ROSE, leverages the additional semantics provided by library-defined abstractions enabling library specific optimization of application codes. It is a common perception that performance is inversely proportional to the level of abstraction. Our work shows that this is not the case if the additional semantics can be leveraged. We show how ROSE can be used to leverage the semantics within the compile-time optimization. Copyright © 2004 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Accurate numerical modeling of complex physical, chemical, and biological systems requires numerical simulation capability over a large range of length scales, with the ability to capture rapidly varying phenomena localized in space and/or time. Adaptive mesh refinement (AMR) is a numerical process for dynamically introducing local fine resolution on computational grids during the solution process, in response to unresolved error in a computation. Fast adaptive composite-grid (FAC) methods are a class of algorithms that exploit the multilevel structure of AMR grids to solve elliptic problems efficiently. This paper develops a theoretical foundation for AFACx, an asynchronous FAC method. A new multilevel condition number estimate establishes that the convergence rate of the AFACx algorithm does not degrade as the number of refinement levels in the AMR hierarchy increases. [ABSTRACT FROM AUTHOR]

Background: Low-molecular-weight heparin has greatly simplified the management of deep venous thrombosis. However, for patients who present with pulmonary embolism, the role of low-molecular-weight heparin is uncertain and unfractionated heparin remains widely used.Purpose: To compare the efficacy and safety of fixed-dose subcutaneous low-molecular-weight heparin with that of dose-adjusted intravenous unfractionated heparin to treat acute pulmonary embolism.Data Sources: The MEDLINE, EMBASE, and Cochrane Library databases were searched up to 1 August 2003. Additional data sources were manual searches of abstract proceedings and personal contact with investigators and pharmaceutical companies.Study Selection: Randomized trials comparing fixed-dose subcutaneous low-molecular-weight heparin with dose-adjusted intravenous unfractionated heparin for the treatment of nonmassive symptomatic pulmonary embolism or asymptomatic pulmonary embolism in the context of symptomatic deep venous thrombosis.Data Extraction: Two reviewers independently selected studies and extracted data on study design; quality; and clinical outcomes, including symptomatic venous thromboembolism, death, and major and minor bleeding. Odds ratios for individual outcomes were calculated for each trial and were pooled by using the Mantel-Haenszel method.Data Synthesis: Fourteen trials involving 2110 patients with pulmonary embolism met the inclusion criteria. Separate outcome data for patients with pulmonary embolism were not available from 2 trials (159 patients), leaving 12 trials for meta-analysis. Compared with unfractionated heparin, low-molecular-weight heparin was associated with a non-statistically significant decrease in recurrent symptomatic venous thromboembolism at the end of treatment (1.4% vs. 2.4%; odds ratio, 0.63 [95% CI, 0.33 to 1.18]) and at 3 months (3.0% vs. 4.4%; odds ratio, 0.68 [CI, 0.42 to 1.09]). Similar estimates were obtained for patients who presented with symptomatic pulmonary embolism (1.7% vs. 2.3%; odds ratio, 0.72 [CI, 0.35 to 1.48]) or asymptomatic pulmonary embolism (1.2% vs. 3.2%; odds ratio, 0.53 [CI, 0.15 to 1.88]). For major bleeding complications, the odds ratio favoring low-molecular-weight heparin (1.3% vs. 2.1%; odds ratio, 0.67 [CI, 0.36 to 1.27]) was also not statistically significant.Conclusions: Fixed-dose low-molecular-weight heparin treatment appears to be as effective and safe as dose-adjusted intravenous unfractionated heparin for the initial treatment of nonmassive pulmonary embolism. [ABSTRACT FROM AUTHOR]

This paper presents numerical results for the asynchronous version of the fast adaptive composite-grid algorithm (AFACx). These results confirm the level-independent convergence bounds established theoretically in a companion paper. These numerical results include the case of AFACx applied to first-order system least-squares finite element discretizations of the stationary Stokes equations on curvilinear adaptive mesh refinement grids. [ABSTRACT FROM AUTHOR]

Background: The prevalence of asymptomatic deep vein thrombosis diagnosed by venography after hip or knee replacement remains high despite 7 to 10 days of anticoagulant prophylaxis. However, the risk of symptomatic events in such patients is unclear. We performed a meta-analysis to provide reliable estimates of the risk of symptomatic venous thromboembolism occurring within 3 months of hip or knee replacement in patients who received shortduration (7-10 days) anticoagulant prophylaxis. Methods: The MEDLINE, EMBASE, and Cochrane databases were searched from January 1993 to March 2001, supplemented by a manual search of bibliographies and conference abstracts, to identify prospective studies of patients undergoing hip or knee replacement who received short-duration prophylaxis (ie, 7-10 days of fixeddose low-molecular-weight heparin or adjusted-dose warfarin, with a target international normalized ratio of 2.0-3.0). Studies were classified as clinical outcome studies if the outcome was symptomatic venous thromboembolism or as venographic outcome studies if the outcome was asymptomatic deep vein thrombosis diagnosed after bilateral venography. Results: There were 4 clinical outcome studies with 6089 patients who had 3 months of follow-up, and 13 venographic outcome studies with 7080 patients who had venography 7 to 10 days after surgery. In clinical outcome studies, the 3-month incidence of nonfatal venous thromboembolism was 3.2% (95% confidence interval [CI], 2.0%-4.4%), and the 3-month incidence of fatal pulmonary embolism was 0.10% (95% CI, 0.02%-0.20%). The postprophylaxis incidence of nonfatal venous thromboembolism was 2.2% (95% CI, 1.4%-3.0%), and the incidence of fatal pulmonary embolism was 0.05% (95% CI, 0%-0.12%). The postprophylaxis incidence of symptomatic venous thromboembolism was higher after hip than after knee replacement (2.5% vs 1.4%; P = .02). In venographic outcome studies, the prevalence of deep vein thrombosis (total and proximal) was... [ABSTRACT FROM AUTHOR]

A letter to the editor is presented in response to the article "Low-Molecular-Weight Heparin as an Adjunct to Thrombolysis in ST Elevation Myocardial Infarction" in the previous issue.

Presents a response by authors to a letter to the editor on their article related to the use of low-molecular-weight Heparin for pulmonary embolism.