bluuebunny/crossref_metadata_2025 huggingface dataset:
A single ubiquitin is sufficient for cargo protein entry into MVBs in the absence of ESCRT ubiquitination
Authors: Stringer Daniel K. , Piper Robert C.
Published: January 2011

ESCRTs (endosomal sorting complexes required for transport) bind and sequester ubiquitinated membrane proteins and usher them into multivesicular bodies (MVBs). As Ubiquitin (Ub)-binding proteins, ESCRTs themselves become ubiquitinated. However, it is unclear whether this regulates a critical aspect of their function or is a nonspecific consequence of their association with the Ub system. We investigated whether ubiquitination of the ESCRTs was required for their ability to sort cargo into the MVB lumen. Although we found that Rsp5 was the main Ub ligase responsible for ubiquitination of ESCRT-0, elimination of Rsp5 or elimination of the ubiquitinatable lysines within ESCRT-0 did not affect MVB sorting. Moreover, by fusing the catalytic domain of deubiquitinating peptidases onto ESCRTs, we could block ESCRT ubiquitination and the sorting of proteins that undergo Rsp5-dependent ubiquitination. Yet, proteins fused to a single Ub moiety were efficiently delivered to the MVB lumen, which strongly indicates that a single Ub is sufficient in sorting MVBs in the absence of ESCRT ubiquitination.
Massive endocytosis driven by lipidic forces originating in the outer plasmalemmal monolayer: a new approach to membrane recycling and lipid domains
Authors: Fine Michael , Llaguno Marc C. , Lariccia Vincenzo , Lin Mei-Jung , Yaradanakul Alp , Hilgemann Donald W.
Published: January 2011

The roles that lipids play in endocytosis are the subject of debate. Using electrical and imaging methods, we describe massive endocytosis (MEND) in baby hamster kidney (BHK) and HEK293 cells when the outer plasma membrane monolayer is perturbed by the nonionic detergents, Triton X-100 (TX100) and NP-40. Some alkane detergents, the amphipathic drugs, edelfosine and tamoxifen, and the phospholipase inhibitor, U73122, are also effective. Uptake of the membrane tracer, FM 4–64, into vesicles and loss of reversible FM 4–64 binding confirm that 40–75% of the cell surface is internalized. Ongoing MEND stops in 2–4 s when amphipaths are removed, and amphipaths are without effect from the cytoplasmic side. Thus, expansion of the outer monolayer is critical. As found for Ca-activated MEND, vesicles formed are <100 nm in diameter, membrane ruffles are lost, and β-cyclodextrin treatments are inhibitory. However, amphipath-activated MEND does not require Ca transients, adenosine triphosphate (ATP) hydrolysis, G protein cycling, dynamins, or actin cytoskeleton remodeling. With elevated cytoplasmic ATP (>5 mM), MEND can reverse completely and be repeated multiple times in BHK and HEK293 cells, but not cardiac myocytes. Reversal is blocked by N-ethylmaleimide and a nitric oxide donor, nitroprusside. Constitutively expressed Na/Ca exchangers internalize roughly in proportion to surface membrane, whereas Na/K pump activities decrease over-proportionally. Sodium dodecyl sulfate and dodecylglucoside do not cause MEND during their application, but MEND occurs rapidly when they are removed. As monitored capacitively, the binding of these detergents decreases with MEND, whereas TX100 binding does not decrease. In summary, nonionic detergents can fractionate the plasma membrane in vivo, and vesicles formed connect immediately to physiological membrane-trafficking mechanisms. We suggest that lateral and transbilayer inhomogeneities of the plasma membrane provide potential energies that, when unbridled by triggers, can drive endocytosis by lipidic forces.
Molecular approaches towards an understanding of loading and unloading of assimilates in higher plants
Authors: Rentsch Doris , Frommer Wolf B.
Published: January 2011

The combination of two sets of molecular tools, namely yeast expression cloning and the possibility of constructing transgenic plants, has allowed analysis of the transport processes occurring at the plasma membrane in higher plants. To date, more than 30 different plant genes for plasma membrane transporters of sugars and amino acids have been identified, mainly by expression cloning. Furthermore, the functional expression of genes in Schizosaccharomyces pombe, Saccharomyces cerevisiae and Xenopus oocytes has been applied to obtain detailed information on the biochemical properties of the transporters. The expression systems have also allowed the purification of the proteins for structural analysis and to study structure-function relationship using mutagenesis approaches. A number of mutants and transgenic plants defective in certain transport properties are available and these will help in understanding the physiology of the long-distance transport of assimilates.
Molecular analysis of plant sugar and amino acid transporters
Authors: Bush Daniel R. , Chiou Tzyy-Jen , Chen Lishan
Published: January 2011

Although plants are photoautotrophic organisms, they are composed of many heterotrophic tissue systems that must import sugars and amino acids in a process known as assimilate partitioning. While the general features of assimilate partitioning were well described by the early 1980s, little was known about the various transport proteins involved in this essential activity associated with multicellular growth. In the past seven years, however, significant progress has been made in describing the transport properties and molecular genetics of these critical transport systems. Initially, these porters were well characterized using purified membrane vesicles and imposed proton electrochemical potential differences. This approach allowed for a detailed analysis of their transport kinetics, bioenergetics, and substrate specificity. Subsequently, several transporters were cloned using differential hybridization and functional complementation of yeast transport mutants. At first, isolation of transporter genes seemed to simplify our understanding by filling in gaps associated with transporter function. However, it has become increasingly clear that assimilate partitioning has many levels of complexity yet to be penetrated. This is best illustrated by the large number of carriers cloned. For example, at least 12 genes encoding putative sugar transporters in the Major Facilitator Superfamily have been identified in plants. Moreover, recent work in this laboratory has demonstrated that a sugar beet member of this superfamily is targeted to the tonoplast membrane, thus implicating that porter in intracellular sugar partitioning. Similar complexity is emerging in the number of plant amino acid transporters identified. Therefore, a detailed analysis of AAP1/NAT2 as a prototypical example of one class of amino acid carriers has been initiated. The topology of this porter is being mapped, and site-directed and random mutagenesis are being used to identify functionally important amino acid residues and protein domains. The major challenges facing this field are to determine the unique contributions made by these many transport systems, to understand their structure and function relationships and, ultimately, to identify the mechanisms which regulate activity and integrate assimilate distribution in the plant as a multicellular organism.
What determines carbon partitioning between competing sinks?
Authors: Minchin P.E.H. , Thorpe M.R.
Published: January 2011

Carbohydrate sinks have been described by their ability to attract photosynthate, denoted by sink strength, and by their priority rank ordering for supply in the presence of a reduced availability of photosynthate. Sink strength has been defined as the rate of carbohydrate flow into a sink, but this flow rate is also dependent upon supply, other sinks, and resistance to flow of the transport pathway, so it is not a property of the sink alone. It is a property of the entire system. Hence sink strength defined as a flow rate is not a valid descriptor of a sink.

However, a simple model of phloem flow based upon Münch's ideas and with saturable unloading has many properties similar to a plant's carbohydrate source-sink relations, including priorities of sinks, and leads to a set of sink descriptors. This model's ability to mimic observed source-sink relations is reviewed here.
Neutral Lipids in Free, Bound, and Starch Lipid Extracts of Flours, Sourdough, and Portuguese Sourdough Bread Determined by NP‐HPLC‐ELSD
Authors: Rocha J. M. , Kalo P. J. , Malcata F. X.
Published: January 2011

A detailed analysis was developed, focused on the neutral lipids (NL) in free (FL), bound (BL), and starch lipid (SL) extracts of maize and rye flours, sourdough, and broa (a traditional bread manufactured in Portugal). Selective sequential extraction of said lipids with hexane at 20°C, water‐saturated n‐butanol at 20°C, and n‐propanol‐water (3:1, v/v) at 100°C was performed to clean the lipid extracts from extraneous impurities, and isolation thereof from glyco‐ and phospholipids was by solid phase extraction of NL; these classes were then quantitatively assayed by HPLC, using evaporative light scattering detection, with calibration curves prepared with standard mixtures of NL. The BL and SL contents in the original flours increased and that of FL decreased throughout the fermentation and baking processes. The dominant NL class was not the same in all lipid extracts; the highest concentrations of triacylglycerols and the lowest concentrations of free fatty acids were detected in FL—with the former accounting for 82, 76, and 71% of the total FL in flours, sourdough, and bread, respectively. Triacylglycerols and free fatty acids also accounted for the highest concentrations found in BL: these, together with diacylglycerols, contributed up to 84% of the total neutral BL. High levels of free fatty acids and low levels of the remaining NL classes were typically found in SL: free fatty acids, triacylglycerols, sterol esters, and diacylglycerols accounted for ≈90% of the total SL.
Multiple Treatment Meta-Analysis of Products Evaluated for Control of Fire Blight in the Eastern United States
Authors: Ngugi H. K. , Lehman B. L. , Madden L. V.
Published: January 2011

The aim of this analysis was to estimate the effect sizes and consistency of products evaluated for fire blight control in the eastern United States over the last decade. Because only 3% of the 69 studies published from 2000 to 2008 explicitly presented a measure of within-study variability, a method for estimating the least significant difference (LSD) and, hence the sampling variance, for studies with at least two significant mean separations in the presented mean multiple comparisons was developed. Lin's concordance analysis indicated that the estimated LSD was an accurate predictor of the actual LSD based on 35 studies in a calibration evaluation (ρc = 0.997). Separate multi-treatment random-effects meta-analyses were performed for three control categories: antibiotics, biological control, and plant defense-activating products and mean log response ratios relative to the nontreated controls ([Formula: see text]) were computed for each treatment and then back-transformed to obtain the mean percent disease control. None of the products evaluated performed as well as streptomycin, the standard product for fire blight control, for which the mean disease control was 68.6%. As a group, experimental antibiotics provided the best fire blight control with mean effect sizes ranging from 59.7 to 61.7%. Among the biological controls, the best control was noted for treatments combining the antibiotic streptomycin with a product based on Pantoea agglomerans (55.0% mean disease reduction) or Bacillus subtilis (53.9%). Mean disease control was 31.9, 25.7, and 22.6%, respectively, for products based on B. subtilis, Pantoea agglomerans, and Pseudomonas fluorescens without an antibiotic, suggesting that the higher efficacy of the combination treatments was due to the antibiotic. Among the plant defense-activating products, prohexadione calcium had the highest and most consistent effect size (50.7% control), while other products provided modest mean disease control of between 6.1 and 25.8%. Percent control values were significantly moderated by study location and cultivar used in the study, and were smaller, but more variable, when products were tested under high disease intensity compared with low disease intensity. Results indicate that wide-scale use of biological control and plant defense-activating products in the eastern United States is likely to remain low.
The genomic landscapes of inflammation
Authors: Natoli Gioacchino , Ghisletti Serena , Barozzi Iros
Published: January 2011

Inflammation involves the activation of a highly coordinated gene expression program that is specific for the initial stimulus and occurs in a different manner in bystander parenchymal cells and professional immune system cells recruited to the inflamed site. Recent data demonstrate that developmental transcription factors like the macrophage fate-determining Pu.1 set the stage for the activity of ubiquitous transcription factors activated by inflammatory stimuli, like NF-kB, AP-1, and interferon regulatory factors (IRFs). The intersection of lineage-determining and stimulus-activated transcription factors at enhancers explains cell type specificity in inflammatory responses.
The nonsense-mediated mRNA decay SMG-1 kinase is regulated by large-scale conformational changes controlled by SMG-8
Authors: Arias-Palomo Ernesto , Yamashita Akio , Fernández Israel S. , Núñez-Ramírez Rafael , Bamba Yumi , Izumi Natsuko , Ohno Shigeo , Llorca Oscar
Published: January 2011

Nonsense-mediated mRNA decay (NMD) is a eukaryotic surveillance pathway that regulates the degradation of mRNAs harboring premature translation termination codons. NMD also influences the expression of many physiological transcripts. SMG-1 is a large kinase essential to NMD that phosphorylates Upf1, which seems to be the definitive signal triggering mRNA decay. However, the regulation of the kinase activity of SMG-1 remains poorly understood. Here, we reveal the three-dimensional architecture of SMG-1 in complex with SMG-8 and SMG-9, and the structural mechanisms regulating SMG-1 kinase. A bent arm comprising a long region of HEAT (huntington, elongation factor 3, a subunit of PP2A and TOR1) repeats at the N terminus of SMG-1 functions as a scaffold for SMG-8 and SMG-9, and projects from the C-terminal core containing the phosphatidylinositol 3-kinase domain. SMG-9 seems to control the activity of SMG-1 indirectly through the recruitment of SMG-8 to the N-terminal HEAT repeat region of SMG-1. Notably, SMG-8 binding to the SMG-1:SMG-9 complex specifically down-regulates the kinase activity of SMG-1 on Upf1 without contacting the catalytic domain. Assembly of the SMG-1:SMG-8:SMG-9 complex induces a significant motion of the HEAT repeats that is signaled to the kinase domain. Thus, large-scale conformational changes induced by SMG-8 after SMG-9-mediated recruitment tune SMG-1 kinase activity to modulate NMD.
Impact on alcohol‐related mortality of a rapid rise in the density of private liquor outlets in British Columbia: a local area multi‐level analysis
Authors: Stockwell Tim , Zhao Jinhui , Macdonald Scott , Vallance Kate , Gruenewald Paul , Ponicki William , Holder Harold , Treno Andrew
Published: January 2011

Aims  To study relationships between rates of alcohol‐related deaths and (i) the density of liquor outlets and (ii) the proportion of liquor stores owned privately in British Columbia (BC) during a period of rapid increase in private stores.

Design  Multi‐level regression analyses assessed the relationship between population rates of private liquor stores and alcohol‐related mortality after adjusting for potential confounding.

Setting  The 89 local health areas of BC, Canada across a 6‐year period from 2003 to 2008, for a longitudinal sample with n = 534.

Measurements  Population rates of liquor store density, alcohol‐related death and socio‐economic variables obtained from government sources.

Findings  The total number of liquor stores per 1000 residents was associated significantly and positively with population rates of alcohol‐related death (P < 0.01). A conservative estimate is that rates of alcohol‐related death increased by 3.25% for each 20% increase in private store density. The percentage of liquor stores in private ownership was also associated independently with local rates of alcohol‐related death after controlling for overall liquor store density (P < 0.05). Alternative models confirmed significant relationships between changes in private store density and mortality over time.

Conclusions  The rapidly rising densities of private liquor stores in British Columbia from 2003 to 2008 was associated with a significant local‐area increase in rates of alcohol‐related death.
Interphase fluorescent in situ hybridization deletion analysis of the 9p21 region and prognosis in childhood acute lymphoblastic leukaemia (ALL): results from a prospective analysis of 519 Nordic patients treated according to the NOPHO‐ALL 2000 protocol
Authors: Kuchinskaya Ekaterina , Heyman Mats , Nordgren Ann , Söderhäll Stefan , Forestier Erik , Wehner Peder , Vettenranta Kim , Jonsson Olafur , Wesenberg Finn , Sahlén Sigrid , Nordenskjöld Magnus , Blennow Elisabeth
Published: January 2011

Interphase fluorescent in situ hybridization (FISH) was applied on diagnostic BM smears from 519 children with acute lymphoblastic leukaemia (ALL) in order to establish the frequency and prognostic importance of 9p21 deletion in children enrolled in the Nordic Society of Paediatric Haematology and Oncology (NOPHO) – 2000 treatment protocol. Among the patients, 452 were diagnosed with B‐cell precursor (BCP)‐ALL and 66 with T‐ALL. A higher incidence of 9p21 deletions was found in T‐ALL (38%) compared to BCP‐ALL (15·7%). Homozygous deletions were found in 19·7% of T‐ALL and 4·0% of BCP‐ALL; hemizygous deletions were found in 18·2% and 11·7% respectively. In our series, 9p21 deletions were detected in all age groups with a steady rise in the frequency with age. There was no significant difference in outcome between cases with or without 9p21 deletion or between cases with hemi‐ or homozygous deletions of 9p21. In conclusion, in this large series of childhood ALL deletion of 9p21 was not associated with worse prognosis. However, interphase FISH deletion analysis of 9p21 could be used as a first step to detect unfavourable subtle cytogenetic aberrations such as the dic(9;20) rearrangement.
Bortezomib and thalidomide, a steroid free regimen in newly diagnosed patients with multiple myeloma
Authors: Ghosh Nilanjan , Ye Xiaobu , Ferguson Anna , Huff Carol Ann , Borrello Ivan
Published: January 2011

Despite their efficacy in myeloma, corticosteroids have acute and chronic toxicities. Newer agents with significant anti‐myeloma activity permit the development of steroid‐free regimens. We designed a Phase II clinical trial to study the toxicity and efficacy of a steroid‐free combination of bortezomib and thalidomide as a first‐line treatment in patients with symptomatic myeloma. Patients received bortezomib 1·3 mg/m2 on days 1, 4, 8 and 11 every 21 d and thalidomide 150 mg/d for a maximum of eight cycles. Amongst 27 evaluable patients, the overall response was 81·5% with 25·8% near complete response or greater. The response rate was comparable to most other two drug combinations for upfront therapy but lower than that obtained with the use of three drugs. The most common grade 3 toxicities were peripheral neuropathy (22%), pneumonia (15%), fatigue (7%) and anaemia (7%). Peripheral neuropathy completely resolved in 80% of the patients upon completion of therapy, but not in the remaining 20% of patients. No venous thromboembolic events were observed even in the absence of prophylactic anticoagulation. The median progression‐free survival was 16·8 months (95% confidence interval 8·7–21·6 months). Median overall survival has not yet been reached at a median follow up of 39 months. The 3‐year overall survival was 74%. This study demonstrates: (i) the efficacy of a steroid‐free regimen; (ii) mostly reversible treatment‐related peripheral neuropathy; and (iii) the absence of venous thrombotic events.
Diversity and invasion within a predator community: impacts on herbivore suppression
Authors: Hogg Brian N. , Daane Kent M.
Published: January 2011

1. Management strategies to enhance ecosystem services in agroecosystems often seek to increase predator biodiversity. Invaders commonly dominate predator communities in agricultural landscapes, however, and the impacts of exotic predators on native predators and ecosystem services are largely unknown. Exotic predators may complement native predator diversity and enhance herbivore suppression, or they may disrupt herbivore suppression through predator interference.

2. We examined the impacts of a dominant exotic predator within the diverse predator community of a California vineyard. Interactions between the exotic wandering spider Cheiracanthium mildei, its closest native ecological homologue (the wandering spider Anyphaena pacifica) and a native spider displaying a different hunting mode (the cobweb‐weaving spider Theridion melanurum) were tested in a manipulative field experiment, with the grape leafhopper Erythroneura elegantula acting as a shared herbivore prey source.

3. We found that the exotic wandering spider suppressed both grape leafhoppers and other unmanipulated leafhopper species that were present in cages. Native spiders had little or no impacts on leafhopper suppression. Thus, C. mildei appears to drive predatory impacts in this system, although evidence also indicated that it is limited by intraspecific interactions. The superior predatory ability displayed by this spider may be shared by other invasive predators that dominate agroecosystems.

4. Despite its effects on leafhoppers, C. mildei negatively impacted a range of spider species, including A. pacifica, T. melanurum, and other unmanipulated native spiders. These impacts are likely to have been mediated through intraguild predation. The wandering hunting mode of C. mildei may have facilitated its role as an intraguild predator.

5. Synthesis and applications. Our results highlight the sometimes conflicting aims of biological control and conservation. Here, a dominant invasive predator increased ecosystem services but also caused declines in numbers of native predators. As disturbed conditions in agroecosystems are likely to put invasive predators at an adaptive advantage, efforts to conserve biodiversity in agricultural landscapes should focus on shifting the outcomes of species interactions to favour native species.
Portal vein obstruction after liver transplantation in children treated by simultaneous minilaparotomy and transhepatic approaches: Initial experience
Authors: Carnevale Francisco C. , Santos Aline C. B. , Seda‐Neto João , Zurstrassen Charles E. , Moreira Airton M. , Carone Eduardo , Marcelino Antonio S. Z. , Porta Gilda , Pugliese Renata , Miura Irene , Baggio Vera D. , Guimarães Teresa , Cerri Giovanni G. , Chapchap Paulo
Published: January 2011

Carnevale FC, Santos ACB, Seda‐Neto J, Zurstrassen CE, Moreira AM, Carone E, Marcelino ASZ, Porta G, Pugliese R, Miura I, Baggio VD, Guimarães T, Cerri GG, Chapchap P. Portal vein obstruction after liver transplantation in children treated by simultaneous minilaparotomy and transhepatic approaches: Initial experience. Pediatr Transplantation 2011: 15: 47–52. © 2011 John Wiley & Sons A/S.

Abstract:  Portal vein thrombosis is a complication that occurs anytime after liver transplantation and can compromise the patient and graft survival. We describe a combined technique for PV recanalization in cases of PV obstruction after liver transplantation. Four children (1%), of 367 subjected to liver transplantation from June 1991 to December 2008, underwent PV recanalization through a combined approach (transhepatic and minilaparotomy). All children received left lateral hepatic segments, developed Portal vein thrombosis (n = 3) and stenosis (n = 1), and presented with symptoms of portal hypertension after transplantation. PV recanalization was tried by transhepatic retrograde access, and a minilaparotomy was performed when percutaneous recanalization was unsuccessful. Three patients underwent a successful portal recanalization and stent placement with the combined technique. In one patient, the recanalization was unsuccessful because of an extensive portomesenteric thrombosis. The other three children had the portal flow reestablished and followed with Doppler US studies. They received oral anticoagulation for three consecutive months after the procedure and the clinical symptoms subsided. In case of PV obstruction, the combined approach is technically feasible with good clinical and hemodynamic results. It’ is a minimally invasive procedure and can be tried to avoid or delay surgical treatment or retransplantation.
Blood pressure or blood flow: Which is important in the preterm infant? A case report of twins
Authors: Shah Dharmesh M , Condò Manuela , Bowen Jennifer , Kluckow Martin
Published: January 2011

There is a poor association between systemic blood flow and blood pressure in preterm infants in the first days of life. Very preterm babies can have early low systemic blood flow with poor myocardial contractility but normal blood pressure. Superior vena cava flow measured by echocardiography can be used to determine systemic blood flow. Low superior vena cava flow is a risk factor for mortality and morbidity in preterm infants.

We report the case of preterm twins with contrasting relationships among systemic blood flow, myocardial contractility and blood pressure. The first twin with normal blood pressure, but low superior vena cava flow and poor myocardial contractility in the first hours of life developed a severe intraventricular haemorrhage and died, despite cardiovascular support. The second twin with low blood pressure but normal superior vena cava flow did not develop adverse outcomes in the first days of life. These cases underline the usefulness of neonatal functional echocardiography in early understanding and management of the preterm infant, and the inaccuracy of other clinical parameters used to assess cardiovascular function.
Anhedonia in Japanese patients with Parkinson's disease
Authors: Fujiwara Shinya , Kimura Fumiharu , Hosokawa Takafumi , Ishida Shimon , Sugino Masakazu , Hanafusa Toshiaki
Published: January 2011

Aim:  Anhedonia has been proposed as a specific mood disorder related to the dopaminergic nerve dysfunction seen in Parkinson's disease (PD). This study examined hedonic tone in patients with PD using the Snaith–Hamilton Pleasure Scale (SHAPS) and investigated the associations with depressive mood by the Self‐Rating Questionnaire for Depression (SRQ‐D).

Methods:  This study examined 100 patients with PD and 111 age‐matched controls (C2) recruited from 300 healthy subjects (C1) to compare the frequency of anhedonia and to clarify whether anhedonia in PD is associated with depression and anti‐Parkinson medication.

Results:  Forty‐six percent of PD patients revealed possible/probable depression and 10 patients (10%) with PD showed anhedonia as compared to 3.3% in C1 and 2.7% in C2. The reduction in hedonic tone was related to depression in PD. Among 10 PD patients with anhedonia, seven were in anhedonia with depression and three were in anhedonia without depression. There was no sex difference in anhedonia and depression. No patients treated with pramipexole showed anhedonia but also the highest proportion of normal hedonic tone was found in patients treated with pramipexole among PD patients. In analysis of each SHAPS item, no significant difference was seen on social interaction scores in contrast to the significant reduction of interest/pastimes and sensory experience and food/drink scores between PD patients and C1/C2.

Conclusion:  Anhedonia may overlap depressive syndrome but some PD patients without depression presented anhedonia. Pramipexole could maintain hedonic tone. The PD patients could enjoy attracting attention and wish to do things helpful for others. Geriatr Gerontol Int 2011; 11: 275–281.
Preliminary experience with external hemipelvectomy for locally advanced and recurrent pelvic carcinoma
Authors: Nielsen M. B. , Rasmussen P. , Keller J. , Laurberg S.
Published: January 2011

Aim  Eight highly selected patients are reported, undergoing external hemipelvectomy (EHP) for malignant infiltration of the lumbosacral neural plexus.

Method  All patients were evaluated by positron emission tomography‐computed tomography (PET‐CT), CT and magnetic resonance imaging. No evidence of disseminated disease was found. With agreement by the multidisciplinary team, surgery was performed by a colorectal surgeon and an orthopaedic sarcoma surgeon and, if needed, by an urologist and vascular surgeon. Patients were reconstructed with either a femoral or a gluteal musculocutaneous flap.

Results  Of the eight women [median age 54.5 (40–68) years], two had primary carcinoma and six local recurrence of a previously treated carcinoma. R0 was possible in six patients and R1 resection in two. The median duration of hospital stay was 29.5 (17–102) days. The median follow up was 8.3 (4.7–52.8) months. Three patients have died, one from postoperative complications at 5 months and two from recurrence at 5 and 52.8 months. Phantom‐limb was experienced in six patients. Four patients received a prosthesis, one is considering this and one does not want a prosthesis.

Conclusion  Hemipelvectomy may be considered for a highly selected group of patients with locally advanced carcinoma or recurrence involving the lumbosacral neural plexus.
Tadalafil administered once daily for lower urinary tract symptoms secondary to benign prostatic hyperplasia: a 1‐year, open‐label extension study
Authors: Donatucci Craig F. , Brock Gerald B. , Goldfischer Evan R. , Pommerville Peter J. , Elion‐Mboussa Albert , Kissel Jay D. , Viktrup Lars
Published: January 2011

Study Type – Therapy (cohort) Level of Evidence 2b

What’s known on the subject? and What does the study add?

Phosphodiesterase type‐5 (PDE5) inhibitors (tadalafil, vardenafil, and sildenafil) are well‐known treatment options for men with erectile dysfunction and should be taken before anticipated sexual activity.

Tadalafil is also approved for once daily use in men with erectile dysfunction. Recent 12‐week studies in men with benign prostatic hyperplasia (BPH) have shown once daily use of tadalafil significantly reduced their urinary symptoms. This article is the first to report the long‐term safety and maintenance of efficacy for once‐daily use of tadalafil in men with urinary symptoms secondary to BPH.

OBJECTIVE

• To evaluate the 1‐year safety of 5 mg of tadalafil once daily in men with lower urinary tract symptoms secondary to benign prostatic hyperplasia (BPH‐LUTS); efficacy measures were included to evaluate the maintenance of efficacy after an additional year of treatment.

PATIENTS AND METHODS

• In total, 427 men who completed a 12‐week, placebo‐controlled, dose‐ finding study assessing once‐daily tadalafil (2.5, 5, 10 or 20 mg) or placebo elected to continue into the open‐label extension period. Safety and efficacy parameters were assessed after 1 month and every 3 months.

RESULTS

• In total, 299 patients (69.9%) completed the 1‐year, open‐label extension period. Treatment‐emergent adverse events (TEAEs) were reported by 57.6% of patients, with most TEAEs being mild (44%) or moderate (45%) in severity; the most common TEAEs (≥2%) were dyspepsia, gastro‐oesophageal reflux disease, back pain, headache, sinusitis, hypertension and cough. Twenty‐two patients (5.2%) discontinued as a result of AEs. During the open‐label extension period, mean prostate‐specific antigen increased from 1.6 ± 1.3 ng/mL to 1.8 ± 1.4 ng/mL.

• Mean post‐void residual volume was 61.1 ± 60.4 mL at study entry and 42.2 ± 64.1 mL after the open‐label extension period. Changes in the total International Prostate Symptom Score (IPSS), IPSS irritative and obstructive subscores, IPSS health‐related quality of life and BPH Impact Index were maintained after 1 year. In sexually‐active patients with erectile dysfunction, improvements in the International Index of Erectile Function–Erectile Function domain were maintained after 1 year.

CONCLUSION

• In men with BPH‐LUTS, 5 mg of tadalafil once daily during 1 year of treatment was well tolerated and efficacy changes were maintained.
Provider and partner interactions in the treatment decision‐making process for newly diagnosed localized prostate cancer
Authors: Zeliadt Steven B. , Penson David F. , Moinpour Carol M. , Blough David K. , Fedorenko Catherine R. , Hall Ingrid J. , Smith Judith Lee , Ekwueme Donatus U. , Thompson Ian M. , Keane Thomas E. , Ramsey Scott D.
Published: January 2011

Study Type – Patient experience (non‐consecutive cohort)

Level of Evidence 3b

What’s known on the subject? and What does the study add?

Decisions about prostate cancer treatment usually involve the patient, the patient’s closest family member (e.g. spouse or partner) and the physician, however no study has examined this “triad” of decision makers in detail. Moreover, no study has evaluated the role that prostate cancer patients’ partners play in the treatment decision‐making process.

This study provides evidence that partners are very involved in the treatment decision making between loved ones and providers and often attend clinic visits. Provider encouragement of partner participation was associated with higher partner satisfaction and an increased likelihood of partners reporting very frequent discussions with their loved ones.

OBJECTIVE

• To evaluate the degree to which the partners of prostate cancer patients participate in the shared decision‐making process with the patients’ providers during the time between diagnosis and initiating treatment.

PATIENTS AND METHODS

• We recruited patients with newly diagnosed local‐stage prostate cancer and their partners to complete take‐home surveys after biopsy but before initiating treatment at urology practices in three states.

• We asked partners to describe their roles in the decision‐making process, including participation in clinic visits, and perceptions of encouragement from providers to participate in the treatment decision‐making process. We also asked partners to rate their satisfaction with the patients’ providers.

RESULTS

• Family members of 80% of newly diagnosed patients agreed to participate; most (93%) were partners (i.e. spouses or significant others). Most partners (93%) had direct contact with the patients’ physicians.

• Among the partners who had contact with providers, most (67%) were very satisfied with the patients’ providers and 80% indicated that the doctor encouraged them to participate in the treatment decision. Overall, 91% of partners reported very frequent discussions with their loved one about the pending treatment decision, and 69% reported that their role was to help the patient make a decision.

• In multivariate models, provider encouragement of partner participation was associated with higher partner satisfaction (odds ratio 3.4, 95% CI 1.4–8.4) and an increased likelihood of partners reporting very frequent discussions with their loved one (odds ratio 6.1, 95% CI 1.3–27.7).

CONCLUSIONS

• Partners often attended clinic visits and were very involved in discussions about treatment options with both loved ones and providers.

• Provider encouragement of participation by partners greatly facilitates shared decision‐making between patients and partners.
Phase I/II trial of subcutaneous interleukin‐2, granulocyte‐macrophage colony‐stimulating factor and interferon‐α in patients with metastatic renal cell carcinoma
Authors: Garcia Jorge A. , Mekhail Tarek , Elson Paul , Wood Laura , Bukowski Ronald M. , Dreicer Robert , Rini Brian I.
Published: January 2011

Study Type – Therapy (individual cohort)

Level of Evidence 2b

OBJECTIVE

• To determine, in a phase I/II trial, the maximum tolerated dose (MTD), clinical activity and safety of concurrent subcutaneous (s.c.) interleukin‐2 (IL‐2), interferon‐α2b (IFN‐α) and granulocyte‐macrophage colony‐stimulating factor (GM‐CSF).

PATIENTS AND METHODS

• Patients with metastatic renal cell carcinoma (RCC) received on a 3+3 trial design escalating doses of s.c. GM‐CSF, IL‐2 and IFN‐α.

• Dose‐limiting toxicities (DLTs) during the first 6‐week cycle were used to determine the MTD.

• A phase II trial was then initiated to determine clinical activity.

RESULTS

• A total of sixty patients were enrolled in the study (phase I = 31; phase II = 29).

• Two DLTs were observed (G3 nausea/vomiting and fatigue) and the MTD was determined to be GM‐CSF 5.0 µg/kg/day, IL‐2 9.0 mIU/m2/day and IFN‐α 5.0 mU/m2/day.

• Patients received a median (range) of four (one to 11) cycles of therapy. G3 adverse events were reported in 10 of 31 (32%) patients.

• The overall response rate was 20% (one complete response and 11 partial responses), including patients who were rendered free of disease with surgery.

• The median progression‐free survival and overall survival were 6.0 and 23.4 months, respectively.

CONCLUSIONS

• Immunotherapy with concurrent s.c. GM‐CSF, IL‐2 and IFN‐α is generally well tolerated.

• The overall response rate observed with this combination continues to show the efficacy of immunotherapy in a selected group of metastatic RCC patients.
External validation of QDSCORE® for predicting the 10‐year risk of developing Type 2 diabetes
Authors: Collins G. S. , Altman D. G.
Published: January 2011

Diabet. Med. 28, 599–607 (2011)

Background  A small number of risk scores for the risk of developing diabetes have been produced but none has yet been widely used in clinical practice in the UK. The aim of this study is to independently evaluate the performance of QDSCORE® for predicting the 10‐year risk of developing diagnosed Type 2 diabetes in a large independent UK cohort of patients from general practice.

Methods  A prospective cohort study of 2.4 million patients (13.6 million person years) aged between 25 and 79 years from 364 practices from the UK contributing to The Health Improvement Network (THIN) database between 1 January 1993 and 20 June 2008.

Results  QDSCORE® showed good performance data when evaluated on a large external data set. The score is well calibrated with reasonable agreement between observed and predicted outcomes. There is a slight underestimation of risk in both men and women aged 60 years and above, although the magnitude of underestimation is small. The ability of the score to differentiate between those who develop diabetes and those who do not is good, with values for the area under the receiver operating characteristic curve exceeding 0.8 for both men and women. Performance data in this external validation are consistent with those reported in the development and internal validation of the risk score.

Conclusions  QDSCORE® has shown to be a useful tool to predict the 10‐year risk of developing Type 2 diabetes in the UK.
Do Financial Systems Converge?
Authors: Antzoulatos Angelos A. , Panopoulou Ekaterini , Tsoumas Chris
Published: January 2011

We apply the new panel convergence methodology developed by Phillips and Sul (2007a) on 13 financial development indices from the World Bank's Financial Development and Structure database, to test for financial system convergence across a large set of industrial and developing countries. Our results indicate that there is no convergence for either the financial systems as a whole or their main segments. Far from decreasing, the differences in the financial systems of the sample countries seemingly persist or even increase over time. These differences are more pronounced for the stock market segment and private credit by banks, and less so for the bond market segment and bank deposits. Moreover, the convergent clubs for most indices transcend the distinction industrial vs developing countries, as well as the distinction bank‐based vs capital‐market‐based financial systems.
Global Integration of Central and Eastern European Financial Markets—The Role of Economic Sentiments
Authors: Beckmann Joscha , Belke Ansgar , Kühl Michael
Published: January 2011

This paper examines the importance of different economic sentiments for the Central and Eastern European countries (CEECs) during the transition process. We first analyze the importance of economic confidence with respect to the CEECs' financial markets. Since the integration of formerly strongly‐regulated markets into global markets can also lead to an increase in the dependence of the CEECs' economies on global sentiments, we also investigate the relationship between global economic sentiments, domestic income, and share prices. Applying a restricted cointegrating VAR (CVAR) framework, which allows us to distinguish between the long‐run and the short‐run dynamics, our results for the short run suggest that economic sentiments are influenced by share prices but also offer some predictive power with respect to the latter. What is more, European sentiments play an important role in particular for the CEECs' income and sentiments.
NOTES OF CASES
Authors: Gray Hamish R.
Published: January 2011

Equitable Priorities and the Matrimonial Home
The Matrimonial Causes (Property And Maintenance) Act, 1958
Authors: K.‐F O.
Published: January 2011

THE Act is intended to give effect to some of the minor Recommendations of the Royal Commission on Marriage and Divorce. They are “minor” if compared with the great problems of family law, such as the dissolution of marriage and the responsibility for the custody and education of children. But each of these small reforms will appear as anything but unimportant to those whom they affect in a practical situation. What is regrettable is the inveterate habit of dealing with these problems piecemeal. Still –‐half a loaf is better than no bread.
The Extent Of Res Ipsa Loquitur
Authors: Lillywhite B.
Published: January 2011

THE decision of the Court of Appeal in Walsh v. Hoist & Co., Ltd.,1 raises many uncertainties about the working of the rule of res ipsa loquitur. The facts of the case were that the plaintiff was lawfully upon the highway when he was struck by a brick. The brick came from a building to which certain substantial structural alterations were being made. It was accepted by all members of the court that a prima facie case of negligence arose against both occupier and contractor because res ipsa loquitur.
Reviews
Authors: Blom‐Cooper L. J. , Hammelmann H. A. , Hammelmann H. A. , Bate S. H. , Borrie Gordon , Giles O. C. , Green L. C. , Mann F. A. , Jackson Paul , Lazar Leonard , de Smith S. A. , Harvey C. P.
Published: January 2011

The Letters of Frederic William Maitland. Edited by C. H. S. Fifoot.

Chitty & Jacob's Queen's Bench Forms. Nineteenth edition. By I. H. Jacob, LL.B.

Studies in Criminal Law. By Norval Morris and Colin Howard.

Ventures in Criminology. Selected Recent Papers. By Sheldon and Eleanor Glueck.

Hendrick the Axe Collector. A Study in juvenile criminal guilt. By Denis Hart.

Forgery Detection–A Practical Guide. By Wilson R. Harrison, M.SC., PH.D.

The Law of Carriage by Inland Transport. Fourth Edition. By Otto Kahn‐Freund, M.A., LL.M., DR.JUR., with the assistance of John Hucker, LL.B.

Chalmers on Bills of Exchange. Thirteenth edition. By David A. L. Smout.

Carver's Carriage by Sea. Eleventh edition. By Raoul P. Colinvaux.

Scrutton on Charter Parties and Bills of Lading. Seventeenth edition. By Sir W. L. McNair, Sir A. Mocatta and M. J. Mustill.

Developments in the Law of the Sea, 1958–1964. The British Institute of International and Comparative Law: International Law Series No. 3.

Linje‐Konferanser og Kartell‐Lovgivning. (With summary in English.) By Arvid Frihagen.

The Sources of the Law of International Trade, with Special Reference to East‐West Trade. Edited by Clive M. Schmitthoff.

The Changing Structure of International Law. By Wolfgang Friedmann.

Protection of Human Rights under the Law. By Gaius Ezejiofor.

Conflict of Interests. International Law in a Divided World. By Rosalyn Higgins.

The Law of Delict. Sixth edition. By R. G. McKerron. [Cape Town: Juta & Co. Ltd. Stocked and distributed in the United Kingdom

An Outline of the Constitutional Development of Malta under British Rule. By Professor the hon. J. J. Cremona, LL. D., B. A. (Malta), B. A. (Lond), PH. D. (Lond.), D. Litt.(Rome), F. R. Hist. S., Attorney‐General and Member of the Consultative Council, Malta.
THE ROLE OF SOLICITORS IN DIVORCE PROCEEDINGS*
Authors: Murch Mervyn
Published: January 2011

“I was walking down the boulevard one day with my sister who was down for a week's holiday. She said off the cuff ‘When are you going to get divorced?’ I said ‘I don't know.’ Seeing a solicitor's office, I said ‘ I'll pop in here’—just the job, just like going in the shop for a loaf of bread. So I sees the receptionist. She said ‘ I'll see if he can see you straight away.’ Well, he gave me an interview straight away. Within an hour everything was done. He told me to bring all the gen I could in a couple of weeks time, which I did and then we got on with the job.”
The Logic of Prison Growht
Authors: von Hirsch Andrew
Published: January 2011

Nils Chrissie, Crime Control as Industry
Copyright and the Death of the Author in Literature and Law
Authors: Bently Lionel
Published: January 2011

Martha Woodmansee and Peter Jaszi, The Construction of Authorship: Textual Appropriation in Law and Literature

David Saunders, Authorship and Copyright
Redrawing the Boundaries of Self‐Defence
Authors: Horder Jeremy
Published: January 2011

Suzanne Uniacke, Permissible Killing: The Self‐Defence Justification for Homicide, Cambridge: Cambridge University Press, 1994, ix + 244 pp, hb £35.00.
Lord Woolf's Access to Justice: Plus ça change…
Authors: Zuckerman A. A. S.
Published: January 2011

The one great principle of the English law is to make business for itself. There is no other principle distinctly, certainly and consistently maintained through all its narrow turnings. Viewed by this light it becomes a coherent scheme, and not the monstrous maze the laity are apt to think it. Let them but once clearly perceive that its grand principle is to make business for itself at their expense, and surely they will cease to grumble. (Dickens, Bleak House, Ch XXXIX)
Factors related to pain during routine photodynamic therapy: a descriptive study of 301 patients
Authors: Miller I.M. , Nielsen J.S. , Lophaven S. , Jemec G.B.E.
Published: January 2011

Background  Pain may be a limiting factor in the use of photodynamic therapy (PDT). The consequences of the pain i.e. the resources spent on pain‐intervention during routine PDT therapy are poorly described.

Objectives  To describe the consequences of pain during PDT by describing the use of pain‐reducing interventions in routine use. We studied the frequency as well as level of pain‐reducing intervention.

Methods  Descriptive data from PDT treated patients. The level of pain‐reducing intervention was graded 0, no intervention; +, cold water spray and ++, pause or nerve block.

Results  Data from 983 PDT treatments on 579 lesions distributed on 301 patients: 56% did not require pain‐reducing intervention, 35% required spraying of cold water, while 9% required pause or nerve block. Ordinate logistic regression revealed an association between lesion size and pain‐reducing intervention: the larger the lesion, the more frequent the intervention. Lesion size did not, however, appear associated with the level of intervention. Intervention was most frequently required when treating the scalp/forehead and the extremities. The scalp/forehead also required the highest level of intervention. No significant association between pain‐reducing intervention and diagnosis, pre‐treatment, gender or age was found.

Conclusions  Pain‐reducing intervention was required in 44% of the PDT treatments. Intervention was particularly required when treating lesions in areas suited for PDT therapy for cosmetic reasons such as the scalp/forehead or extremities. Treatment of large areas more frequently calls for pain intervention than treatment of small areas.