bluuebunny/crossref_metadata_2025 huggingface dataset:
Exploring the effects of task shifting for HIV through a systems thinking lens: the case of Burkina Faso
Authors: Yaya Bocoum Fadima , Kouanda Seni , Kouyaté Bocar , Hounton Sennen , Adam Taghreed
Published: October 2013

Background

While the impact of task shifting on quality of care and clinical outcomes has been demonstrated in several studies, evidence on its impact on the health system as a whole is limited. This study has two main objectives. The first is to conceptualize the wider range of effects of task shifting through a systems thinking lens. The second is to explore these effects using task shifting for HIV in Burkina Faso as a case study.

Methods

We used a case study approach, using qualitative research methods. Data sources included document reviews, reviews of available data and records, as well as interviews with key informants and health workers.

Results

In addition to the traditional measures of impact of task shifting on health outcomes, our study identified 20 possible effects of the strategy on the system as a whole. Moreover, our analysis highlighted the importance of differentiating between two types of health systems effects. The first are effects inherent to the task shifting strategy itself, such as job satisfaction or better access to health services. The second are effects due to health system barriers, for example the unavailability of medicines and supplies, generating a series of effects on the various components of the health system, e.g., staff frustration.

Among the health systems effects that we found are positive, mostly unintended, effects and synergies such as increased health workers' sense of responsibility and worthiness, increased satisfaction due to using the newly acquired skills in other non-HIV tasks, as well as improved patient-provider relationships. Among the negative unintended effects are staff frustration due to lack of medicines and supplies or lack of the necessary infrastructure to be able to perform the new tasks.

Conclusion

Our analysis highlights the importance of adopting a systems thinking approach in designing, implementing and evaluating health policies to mitigate some of the design issues or system bottle-necks that may impede their successful implementation or risk to present an incomplete or misleading picture of their impact.
Elevated C-reactive protein values predict nodal metastasis in patients with penile cancer
Authors: Al Ghazal Andreas , Steffens Sandra , Steinestel Julie , Lehmann Rieke , Schnoeller Thomas J , Schulte-Hostede Anna , Wegener Gerd , Jentzmik Florian , Schrader Mark , Kuczyk Markus A , Schrader Andres J
Published: October 2013

Background

The nodal status is a strong predictor for cancer specific death in patients with penile carcinoma, and the C-reactive protein (CRP) level at diagnosis has recently been shown to be associated with poor clinical outcome in various solid malignancies. Therefore, this retrospective study was performed to evaluate the association between preoperative CRP levels and the incidence of nodal metastasis in patients with squamous cell carcinoma (SCC) of the penis.

Methods

The analysis included 51 penile cancer patients who underwent either radical or partial penectomy for pT1-4 penile cancer between 1990 and 2010. The nodal status was correlated with patient and tumor specific characteristics.

Results

Sixteen (31%) patients had lymph node metastasis at the time of penile cancer surgery. Nodal status was associated with tumor stage but did not correlate significantly with tumor grade. In contrast, high presurgical CRP levels were significantly associated with the diagnosis of nodal involvement (p = 0.04). The optimal CRP cut-off value to predict lymph node metastasis was set at 20 mg/l based on ROC analysis.

Conclusions

Since a high preoperative serum CRP level was closely correlated with nodal disease, it could be used as an additional marker to help identify patients with penile cancer who may benefit from inguinal lymph node dissection.
The flavokawains: uprising medicinal chalcones
Authors: Abu Nadiah , Ho Wan Yong , Yeap Swee Keong , Akhtar M Nadeem , Abdullah Mohd Puad , Omar Abdul Rahman , Alitheen Noorjahan Banu
Published: October 2013

Plant-based compounds have been in the spotlight in search of new and promising drugs. Flavokawain A, B and C are naturally occurring chalcones that have been isolated from several medicinal plants; namely the piper methysticum or commercially known as the kava-kava. Multiple researches have been done to evaluate the bioactivities of these compounds. It has been shown that all three flavokawains may hold promising anti-cancer effects. It has also been revealed that both flavokawain A and B are involved in the induction of cell cycle arrest in several cancer cell lines. Nevertheless, flavokawain B was shown to be more effective in treating in vitro cancer cell lines as compared to flavokawain A and C. Flavokawain B also exerts antinociceptive effects as well as anti-inflammation properties. This mini-review attempts to discuss the biological properties of all the flavokawains that have been reported.
Osteomyelitis of the femur mimicking bone tumors: a review of 10 cases
Authors: Huang Po-Yen , Wu Po-Kuei , Chen Cheng-Fong , Lee Fang-Tsai , Wu Hung-Ta , Liu Chien-Lin , Chen Tain-Hsiung , Chen Wei-Ming
Published: October 2013

Background

The clinical symptoms and radiographic appearance of osteomyelitis can mimic those of bone tumors.

Methods

We reviewed 10 patients with osteomyelitis of the femur who were initially diagnosed as having bone tumors and were subsequently transferred to our institution.

Results

Nocturnal pain of moderate intensity occurred in seven patients, and all 10 patients had elevated C-reactive protein levels. The radiographic findings included the following: a permeative, moth-eaten osteolytic lesion in six patients, an osteolytic lesion with sclerotic borders in three patients, and cortical destruction with pathological fracture in one patient. Magnetic resonance imaging was performed for eight patients, and only one had a positive penumbra sign. All patients underwent a surgical biopsy to confirm the final diagnosis for histological analysis and cultures.Klebsiella pneumoniaewas detected in six patients andStaphylococcus aureus, the most common organism in osteomyelitis, was detected in three. Recurrence of infection occurred in five patients following debridement surgery; of these three had aKlebsiella pneumoniaeinfection. All patients received antibiotic treatment for an average of 20.4 weeks (range, 4 to 44) and surgical treatment an average of 1.8 times (range, 1 to 4). At the final follow-up, all patients were fully recovered with no signs of infection.

Conclusions

When used in combination, clinical examinations, laboratory data, and radiographic findings can reliably distinguishing osteomyelitis from bone tumors.
Large-area high-performance SERS substrates with deep controllable sub-10-nm gap structure fabricated by depositing Au film on the cicada wing
Authors: Jiwei Qi , Yudong Li , Ming Yang , Qiang Wu , Zongqiang Chen , Wudeng Wang , Wenqiang Lu , Xuanyi Yu , Jingjun Xu , Qian Sun
Published: October 2013

Noble metal nanogap structure supports strong surface-enhanced Raman scattering (SERS) which can be used to detect single molecules. However, the lack of reproducible fabrication techniques with nanometer-level control over the gap size has limited practical applications. In this letter, by depositing the Au film onto the cicada wing, we engineer the ordered array of nanopillar structures on the wing to form large-area high-performance SERS substrates. Through the control of the thickness of the Au film deposited onto the cicada wing, the gap sizes between neighboring nanopillars are fine defined. SERS substrates with sub-10-nm gap sizes are obtained, which have the highest average Raman enhancement factor (EF) larger than 2 × 108, about 40 times as large as that of commercial Klarite® substrates. The cicada wings used as templates are natural and environment-friendly. The depositing method is low cost and high throughput so that our large-area high-performance SERS substrates have great advantage for chemical/biological sensing applications.
Is there a role for high dose chemotherapy and blood stem cell rescue in childhood hepatoblastoma presenting with lung metastases? A case report and literature review
Authors: Provenzi Massimo , Saettini Francesco , Conter Valentino , Giraldi Eugenia , Foglia Carlo , Cavalleri Laura , Colledan Michele , D’Antiga Lorenzo , Perilongo Giorgio , Da Dalt Liviana
Published: October 2013

We report the use of high dose chemotherapy with peripheral blood stem cell rescue as a consolidation treatment for a 3-year-old child affected by metastatic hepatoblastoma, who achieved complete lung response only after conventional treatment. The patient is presently alive 27 months after high dose chemotherapy with blood stem cell rescue with no evidence of disease.

The role of high dose chemotherapy with blood stem cell rescue to consolidate the complete clearing of lung disease in metastatic hepatoblastoma remains controversial; the data available in the literature and our experience seems to suggest to keep this treatment option open to further consideration in the clinical setting of high-risk patients.
Stereotactic biopsy of the breast using a decubitus table: comparison of histologic underestimation rates between 11- and 8-gauge vacuum-assisted breast biopsy
Authors: Lee Kyoung Eun , Kim Hak Hee , Shin Hee Jung , Cha Joo Hee
Published: October 2013

Purpose

To evaluate efficacy of the stereotactic vacuum-assisted breast biopsy(SVAB) using a decubitus table and to compare histologic underestimation rate between 11gauge(G)- and 8G-probes.

Materials and methods

Pathologic results of SVAB using a decubitus table of 210(120 with 11G; 90 with 8G)-procedures in 208-women(median age, 48.8 years; range, 27-73 years) were retrospectively reviewed. SVAB was performed for suspicious microcalcification without mass on MMG and US. Surgury was performed for the diagnosis of malignant or high-risk lesion (65(31.0%)). Patients with benign diagnosis (120(57.1%)) underwent MMG follow-up (mean, 340-days). Histologic underestimation was defined as the need to upgrade ADH to DCIS or IDC, and DCIS to IDC at surgery. We analyzed the difference of procedure time, core number and core weight between 11G- and 8G-groups. Statistical significance was determined with chi-square test and 95%-CI for histologic underestimation, and student T-test for comparing two-groups.

Results

Targeting was successful in all 210-biopsies on specimen radiographs. Mean core number, core weight and procedure time were 17.5 (17.5 ± 4.9), 1.57 g (1.57 ± 0.56), 34.5 min (34.5 ± 16.4) with 11G-probe, and 9.6 (9.6 ± 6.2), 1.83g (1.83 ± 0.93), 22.1 min (22.1 ± 12.5) with 8G-probe. Findings in 120 (57.1%) of the biopsies were benign, 36 (17.2%) were high-risk, and 54 (25.7%) were malignant. Two (6.25%) of 32 cases of ADH were upgraded to DCIS in 11G-group, and 2 (9.09%) of 22 in 8G-group. No case of DCIS was upgraded to IDC. There was no increase of complication in 8G-group than 11G-group.

Conclusion

SVAB using a decubitus table is safe and effective method for the evaluation of suspicious microcalcification, and there was no significant difference between 11G- and 8G-probes. But, SVAB with 8G-probe is significantly more time efficient and effective procedure.
Prevalence of HLA-B27 in the New Zealand population: effect of age and ethnicity
Authors: Roberts Rebecca L , Wallace Mary C , Jones Gregory T , van Rij Andre M , Merriman Tony R , Harrison Andrew , White Douglas , Stamp Lisa K , Ching Daniel , Highton John , Stebbings Simon M
Published: October 2013

Introduction

HLA-B27 genotyping is commonly used to support a diagnosis of ankylosing spondylitis (AS). A recent study has suggested that HLA-B27 may adversely affect longevity. The objectives of this study were to determine, for the first time, the prevalence of HLA-B27 in the New Zealand population, and to test whether HLA-B27 prevalence declines with age.

Methods

117 Caucasian controls, 111 New Zealand Māori controls, and 176 AS patients were directly genotyped for HLA-B27 using PCR-SSP. These participants and a further 1103 Caucasian controls were genotyped for the HLA-B27 tagging single nucleotide polymorphisms (SNPs) rs4349859 and rs116488202. All AS patients testing positive for HLA-B27 of New Zealand Māori ancestry underwent high resolution typing to determine sub-allele status.

Results

HLA-B27 prevalence was 9.2% in New Zealand Caucasian controls and 6.5% in Māori controls. No decline in HLA-B27 prevalence with age was detected in Caucasian controls (p = 0.92). Concordance between HLA-B27 and SNP genotypes was 98.7-99.3% in Caucasians and 76.9-86% in Māori. Of the 14 AS patients of Māori ancestry, 1 was negative for HLA-B27, 10 were positive for HLAB*2705, and 3 positive for HLAB*2704. All cases of genotype discordance were explained by the presence of HLAB*2704.

Conclusions

HLA-B27 prevalence in New Zealand Caucasians is consistent with that of Northern European populations and did not decline with increasing age. In Māori with AS who were HLA-B27 positive, 76.9% were positive for HLA-B*2705, suggesting that genetic susceptibility to AS in Māori is primarily due to admixture with Caucasians.
Pattern of recurrence of early breast cancer is different according to intrinsic subtype and proliferation index
Authors: Ribelles Nuria , Perez-Villa Lidia , Jerez Jose Manuel , Pajares Bella , Vicioso Luis , Jimenez Begoña , de Luque Vanessa , Franco Leonardo , Gallego Elena , Marquez Antonia , Alvarez Martina , Sanchez-Muñoz Alfonso , Perez-Rivas Luis , Alba Emilio
Published: October 2013

Introduction

Recurrence risk in breast cancer varies throughout the follow-up time. We examined if these changes are related to the level of expression of the proliferation pathway and intrinsic subtypes.

Methods

Expression of estrogen and progesterone receptor, Ki-67, human epidermal growth factor receptor 2 (HER2), epidermal growth factor receptor (EGFR) and cytokeratin 5/6 (CK 5/6) was performed on tissue-microarrays constructed from a large and uniformly managed series of early breast cancer patients (N = 1,249). Subtype definitions by four biomarkers were as follows: luminal A (ER + and/or PR+, HER2-, Ki-67 <14), luminal B (ER + and/or PR+, HER2-, Ki-67 ≥14), HER2-enriched (any ER, any PR, HER2+, any Ki-67), triple-negative (ER-, PR-, HER2-, any Ki-67). Subtype definitions by six biomarkers were as follows: luminal A (ER + and/or PR+, HER2-, Ki-67 <14, any CK 5/6, any EGFR), luminal B (ER + and/or PR+, HER2-, Ki-67 ≥14, any CK 5/6, any EGFR), HER2-enriched (ER-, PR-, HER2+, any Ki-67, any CK 5/6, any EGFR), Luminal-HER2 (ER + and/or PR+, HER2+, any Ki-67, any CK 5/6, any EGFR), Basal-like (ER-, PR-, HER2-, any Ki-67, CK5/6+ and/or EGFR+), triple-negative nonbasal (ER-, PR-, HER2-, any Ki-67, CK 5/6-, EGFR-). Each four- or six-marker defined intrinsic subtype was divided in two groups, with Ki-67 <14% or with Ki-67 ≥14%. Recurrence hazard rate function was determined for each intrinsic subtype as a whole and according to Ki-67 value.

Results

Luminal A displayed a slow risk increase, reaching its maximum after three years and then remained steady. Luminal B presented most of its relapses during the first five years. HER2-enriched tumors show a peak of recurrence nearly twenty months post-surgery, with a greater risk in Ki-67 ≥14%. However a second peak occurred at 72 months but the risk magnitude was greater in Ki-67 <14%. Triple negative tumors with low proliferation rate display a smooth risk curve, but with Ki-67 ≥14% show sharp peak at nearly 18 months.

Conclusions

Each intrinsic subtype has a particular pattern of relapses over time which change depending on the level of activation of the proliferation pathway assessed by Ki-67. These findings could have clinical implications both on adjuvant treatment trial design and on the recommendations concerning the surveillance of patients.
Six-month survival and quality of life of intensive care patients with acute kidney injury
Authors: Nisula Sara , Vaara Suvi T , Kaukonen Kirsi-Maija , Reinikainen Matti , Koivisto Simo-Pekka , Inkinen Outi , Poukkanen Meri , Tiainen Pekka , Pettilä Ville , Korhonen Anna-Maija ,   the FINNAKI-QOL Study Group
Published: October 2013

Introduction

Acute kidney injury (AKI) has high incidence among the critically ill and associates with dismal outcome. Not only the long-term survival, but also the quality of life (QOL) of patients with AKI is relevant due to substantial burden of care regarding these patients. We aimed to study the long-term outcome and QOL of patients with AKI treated in intensive care units.

Methods

We conducted a predefined six-month follow-up of adult intensive care unit (ICU) patients from the prospective, observational, multi-centre FINNAKI study. We evaluated the QOL of survivors with the EuroQol (EQ-5D) questionnaire. We included all participating sites with at least 70% rate of QOL measurements in the analysis.

Results

Of the 1,568 study patients, 635 (40.5%, 95% confidence interval (CI) 38.0-43.0%) had AKI according to the Kidney Disease Improving Global Outcomes (KDIGO) criteria. Of the 635 AKI patients, 224 (35.3%), as compared to 154/933 (16.5%) patients without AKI, died within six months. Of the 1,190 survivors, 959 (80.6%) answered the EQ-5D questionnaire at six months. The QOL (median with Interquartile range, IQR) measured with the EQ-5D index and compared to age- and sex-matched general population was: 0.676 (0.520-1.00) versus 0.826 (0.812-0.859) for AKI patients, and 0.690 (0.533-1.00) versus 0.845 (0.812-0.882) for patients without AKI (P <0.001 in both). The EQ-5D at the time of ICU admission was available for 774 (80.7%) of the six-month respondents. We detected a mean increase of 0.017 for non-AKI and of 0.024 for AKI patients in the EQ-5D index (P = 0.728). The EQ-5D visual analogue scores (median with IQR) of patients with AKI (70 (50–83)) and patients without AKI (75 (60–87)) were not different from the age- and sex-matched general population (69 (68–73) and 70 (68–77)).

Conclusions

The health-related quality of life of patients with and without AKI was already lower on ICU admission than that of the age- and sex-matched general population, and did not change significantly during critical illness. Patients with and without AKI rate their subjective health to be as good as age and sex-matched general population despite statistically significantly lower QOL indexes measured by EQ-5D.
Suspected ventilator-associated respiratory infection in severely ill patients: a prospective observational study
Authors: Shahin Jason , Bielinski Michael , Guichon Celine , Flemming Catherine , Kristof Arnold S
Published: October 2013

Introduction

Ventilator-associated respiratory infection (VARI) is an important cause of morbidity in critically-ill patients. Clinical trials performed in heterogeneous populations have suggested there are limited benefits from invasive diagnostic testing to identify patients at risk or to target antimicrobial therapy. However, multiple patient subgroups (for example, immunocompromised, antibiotic-treated) have traditionally been excluded from randomization. We hypothesized that a prospective surveillance study would better identify patients with suspected VARI (sVARI) at high risk for adverse clinical outcomes, and who might be specifically targeted in future trials.

Methods

We performed a prospective observational study in all patients ventilated for greater than 48 hours. sVARI was identified by surveillance for changes in white blood cell count, temperature, sputum, and/or new chest X-ray infiltrates. Indices of disease co-morbidity, as well as mortality, duration of mechanical ventilation, and length of hospital or ICU stay were correlated with sVARI.

Results

Of 1806 patients admitted to the ICU over 14 months, 267 were ventilated for greater than 48 hours, and 77 developed sVARI. Incidence of sVARI was associated with iatrogenic immunosuppression or admission for respiratory illness. Any sVARI, whether suspected ventilator-associated pneumonia (sVAP) or ventilator-associated tracheobronchitis (sVAT), was associated with increased length of stay and duration of mechanical ventilation.

Conclusions

Clinical surveillance for sVARI identifies patients at risk for increased morbidity. Iatrogenically immunosuppressed patients, a subgroup previously excluded from randomized clinical trials, represent a growing proportion of the critically-ill at risk for sVARI who might be targeted for future investigations on diagnostic or therapeutic modalities.
A Cerebral Recovery Index (CRI) for early prognosis in patients after cardiac arrest
Authors: Tjepkema-Cloostermans Marleen C , van Meulen Fokke B , Meinsma Gjerrit , van Putten Michel JAM
Published: October 2013

Introduction

Electroencephalogram (EEG) monitoring in patients treated with therapeutic hypothermia after cardiac arrest may assist in early outcome prediction. Quantitative EEG (qEEG) analysis can reduce the time needed to review long-term EEG and makes the analysis more objective. In this study, we evaluated the predictive value of qEEG analysis for neurologic outcome in postanoxic patients.

Methods

In total, 109 patients admitted to the ICU for therapeutic hypothermia after cardiac arrest were included, divided over a training and a test set. Continuous EEG was recorded during the first 5 days or until ICU discharge. Neurologic outcomes were based on the best achieved Cerebral Performance Category (CPC) score within 6 months. Of the training set, 27 of 56 patients (48%) and 26 of 53 patients (49%) of the test set achieved good outcome (CPC 1 to 2). In all patients, a 5 minute epoch was selected each hour, and five qEEG features were extracted. We introduced the Cerebral Recovery Index (CRI), which combines these features into a single number.

Results

At 24 hours after cardiac arrest, a CRI <0.29 was always associated with poor neurologic outcome, with a sensitivity of 0.55 (95% confidence interval (CI): 0.32 to 0.76) at a specificity of 1.00 (CI, 0.86 to 1.00) in the test set. This results in a positive predictive value (PPV) of 1.00 (CI, 0.73 to 1.00) and a negative predictive value (NPV) of 0.71 (CI, 0.53 to 0.85). At the same time, a CRI >0.69 predicted good outcome, with a sensitivity of 0.25 (CI, 0.10 to 0.14) at a specificity of 1.00 (CI, 0.85 to 1.00) in the test set, and a corresponding NPV of 1.00 (CI, 0.54 to 1.00) and a PPV of 0.55 (CI, 0.38 to 0.70).

Conclusions

We introduced a combination of qEEG measures expressed in a single number, the CRI, which can assist in prediction of both poor and good outcomes in postanoxic patients, within 24 hours after cardiac arrest.
Open-Phylo: a customizable crowd-computing platform for multiple sequence alignment
Authors: Kwak Daniel , Kam Alfred , Becerra David , Zhou Qikuan , Hops Adam , Zarour Eleyine , Kam Arthur , Sarmenta Luis , Blanchette Mathieu , Waldispühl Jérôme
Published: October 2013

Citizen science games such as Galaxy Zoo, Foldit, and Phylo aim to harness the intelligence and processing power generated by crowds of online gamers to solve scientific problems. However, the selection of the data to be analyzed through these games is under the exclusive control of the game designers, and so are the results produced by gamers. Here, we introduce Open-Phylo, a freely accessible crowd-computing platform that enables any scientist to enter our system and use crowds of gamers to assist computer programs in solving one of the most fundamental problems in genomics: the multiple sequence alignment problem.
Assessment of immunosuppressive activity of human mesenchymal stem cells using murine antigen specific CD4 and CD8 T cells in vitro
Authors: Nazarov Cristina , Surdo Jessica Lo , Bauer Steven R , Wei Cheng-Hong
Published: October 2013

Introduction

Mesenchymal stem cells (MSCs) have immunosuppressive activity. They do not induce allospecific T cell responses, making them promising tools for reducing the severity of graft versus host disease (GVHD) as well as treating various immune diseases. Currently, there is a need in the MSC field to develop a robust in vitro bioassay which can characterize the immunosuppressive function of MSCs.

Methods

Murine clonal CD4 and CD8 T cells were stimulated with cognate peptide antigen and antigen presenting cells (APCs) in the absence or presence of human MSCs, different aspects of T cell activation were monitored and analyzed using flow cytometery, real time RT-PCR and cytokine measurement.

Results

Human MSCs (hMSCs) can alter multiple aspects of murine T cell activation induced by stimulation with specific antigen, including: reduced proliferation, inhibited or stimulated cell surface marker expression (CD25, CD69, CD44 and CD62L), inhibited mRNA expression of transcription factors (T-bet and GATA-3) and decreased cytokine expression (interferon-gamma, interleukin-10). Disappearance of activation-induced cluster formation and decreased apoptosis of CD8 T cells were also observed. Moreover, the effects are specific to MSCs; incubating the T cells with non-MSC control cell lines had no effect on T cell proliferation and activation.

Conclusions

Clonal murine T cells can be used to measure, characterize, and quantify the in vitro immunosuppressive activity of human MSCs, representing a promising approach to improve bioassays for immunosuppression.
Azimuthal anisotropy from OBS observations in Mahanadi offshore, India
Authors: Satyavani Nittala , Sen Mrinal K. , Ojha Maheswar , Sain Kalachand
Published: October 2013

We have carried out an ocean bottom seismometer (OBS) survey in a grid along with multichannel seismic survey for gas hydrate exploration in the Mahanadi offshore, India. Here, we report on some interesting observations in seismic waveform data and their interpretations. These include sudden amplitude dimming in the multichannel data that is azimuth- and space-dependent and a clear manifestation of seismic anisotropy in the region. We observe significant patterns of shear wave splitting in the azimuthal gathers in the OBS data, clearly isolating the fast (S1) and slow (S2) axes of propagation in the radial azimuthal gathers. Further, amplitude nulls and amplitude maxima are observed in the transverse azimuthal gathers. These two features are diagnostic of the existence and orientation of anisotropy which is also modeled by generating full waveform synthetic seismograms. We interpret the occurrence of anisotropy to be due to the presence of fractures. The strike of this fracture set is inferred to be [Formula: see text] from the S1 and S2 orientation and variation in the P-wave amplitude with azimuth. The density of fracture network is estimated by full wave modeling of the OBS data. A good match between the synthetic and observed data is noticed for a near vertical fracture (dip angle of about 85°). The seismic image obtained from the 2D high-resolution multichannel profiles correlate well with the OBS results. Based on these analyses, we are able to delineate a fracture zone, which is linked to the near vertical faulting in the gas hydrate layers.
Progression in Smoldering Myeloma Is Independently Determined by the Chromosomal Abnormalities del(17p), t(4;14), Gain 1q, Hyperdiploidy, and Tumor Load
Authors: Neben Kai , Jauch Anna , Hielscher Thomas , Hillengass Jens , Lehners Nicola , Seckinger Anja , Granzow Martin , Raab Marc S. , Ho Anthony D. , Goldschmidt Hartmut , Hose Dirk
Published: October 2013

Purpose

The aim of this study was to analyze chromosomal aberrations in terms of frequency and impact on time to progression in patients with smoldering multiple myeloma (SMM) on the background of clinical prognostic factors.

Patients and Methods

The chromosomal abnormalities 1q21, 5p15/5q35, 9q34, 13q14.3, 15q22, 17p13, t(11;14)(q13;q32), and t(4;14)(p16.3;q32) were assessed in CD138-purified myeloma cells by interphase fluorescent in situ hybridization (iFISH) alongside clinical parameters in a consecutive series of 248 patients with SMM.

Results

The high-risk aberrations in active myeloma (ie, del(17p13), t(4;14), and +1q21) present in 6.1%, 8.9%, and 29.8% of patients significantly confer adverse prognosis in SMM with hazard ratios (HRs) of 2.90 (95% CI, 1.56 to 5.40), 2.28 (95% CI, 1.33 to 3.91), and 1.66 (95% CI, 1.08 to 2.54), respectively. Contrary to the conditions in active myeloma, hyperdiploidy, present in 43.3% of patients, is an adverse prognostic factor (HR, 1.67; 95% CI, 1.10 to 2.54). Percentage of malignant bone marrow plasma cells assessed by iFISH and combination of M-protein and plasma cell infiltration as surrogates of tumor load significantly confer adverse prognosis with HRs of 4.37 (95% CI, 2.79 to 6.85) and 4.27 (95% CI, 2.77 to 6.56), respectively. In multivariate analysis, high-risk aberrations, hyperdiploidy, and surrogates of tumor load are independently prognostic.

Conclusion

The high-risk chromosomal aberrations del(17p13), t(4;14), and +1q21 are adverse prognostic factors in SMM just as they are in active myeloma, independent of tumor mass. Hyperdiploidy is the first example for an adverse prognostic factor in SMM of opposite predictiveness in active myeloma. Risk association of chromosomal aberrations is not only a priori treatment dependent (predictive) but is also an intrinsic property of myeloma cells (prognostic).
Dose-Limiting Toxicity After Hypofractionated Dose-Escalated Radiotherapy in Non–Small-Cell Lung Cancer
Authors: Cannon Donald M. , Mehta Minesh P. , Adkison Jarrod B. , Khuntia Deepak , Traynor Anne M. , Tomé Wolfgang A. , Chappell Richard J. , Tolakanahalli Ranjini , Mohindra Pranshu , Bentzen Søren M. , Cannon George M.
Published: October 2013

Purpose

Local failure rates after radiation therapy (RT) for locally advanced non–small-cell lung cancer (NSCLC) remain high. Consequently, RT dose intensification strategies continue to be explored, including hypofractionation, which allows for RT acceleration that could potentially improve outcomes. The maximum-tolerated dose (MTD) with dose-escalated hypofractionation has not been adequately defined.

Patients and Methods

Seventy-nine patients with NSCLC were enrolled on a prospective single-institution phase I trial of dose-escalated hypofractionated RT without concurrent chemotherapy. Escalation of dose per fraction was performed according to patients' stratified risk for radiation pneumonitis with total RT doses ranging from 57 to 85.5 Gy in 25 daily fractions over 5 weeks using intensity-modulated radiotherapy. The MTD was defined as the maximum dose with ≤ 20% risk of severe toxicity.

Results

No grade 3 pneumonitis was observed and an MTD for acute toxicity was not identified during patient accrual. However, with a longer follow-up period, grade 4 to 5 toxicity occurred in six patients and was correlated with total dose (P = .004). An MTD was identified at 63.25 Gy in 25 fractions. Late grade 4 to 5 toxicities were attributable to damage to central and perihilar structures and correlated with dose to the proximal bronchial tree.

Conclusion

Although this dose-escalation model limited the rates of clinically significant pneumonitis, dose-limiting toxicity occurred and was dominated by late radiation toxicity involving central and perihilar structures. The identified dose-response for damage to the proximal bronchial tree warrants caution in future dose-intensification protocols, especially when using hypofractionation.
Rational design of microRNA–siRNA chimeras for multifunctional target suppression
Authors: Jiang Zhou , Liu Weijun , Wang Yuhui , Gao Zhen , Gao Ge , Wang Xiaowei
Published: October 2013

MicroRNAs (miRNAs) are involved in a variety of human diseases by simultaneously suppressing many gene targets. Thus, the therapeutic value of miRNAs has been intensely studied. However, there are potential limitations with miRNA-based therapeutics such as a relatively moderate impact on gene target regulation and cellular phenotypic control. To address these issues, we proposed to design new chimeric small RNAs (aiRNAs) by incorporating sequences from both miRNAs and siRNAs. These aiRNAs not only inherited functions from natural miRNAs, but also gained new functions of gene knockdown in an siRNA-like fashion. The improved efficacy of multifunctional aiRNAs was demonstrated in our study by design and testing of an aiRNA that inherited the functions of both miR-200a and an AKT1-targeting siRNA for simultaneous suppression of cancer cell motility and proliferation. The general principles of aiRNA design were further validated by engineering new aiRNAs mimicking another miRNA, miR-9. By regulating multiple cellular functions, aiRNAs could be used as an improved tool over miRNAs to target disease-related genes, thus alleviating our dependency on a limited number of miRNAs for the development of RNAi-based therapeutics.
Surgical treatment of severe congenital thoracolumbar kyphosis through a single posterior approach
Authors: Spiro A. S. , Rupprecht M. , Stenger P. , Hoffman M. , Kunkel P. , Kolb J. P. , Rueger J. M. , Stuecker R.
Published: October 2013

A combined anterior and posterior surgical approach is generally recommended in the treatment of severe congenital kyphosis, despite the fact that the anterior vascular supply of the spine and viscera are at risk during exposure. The aim of this study was to determine whether the surgical treatment of severe congenital thoracolumbar kyphosis through a single posterior approach is feasible, safe and effective.

We reviewed the records of ten patients with a mean age of 11.1 years (5.4 to 14.1) who underwent surgery either by pedicle subtraction osteotomy or by vertebral column resection with instrumented fusion through a single posterior approach.

The mean kyphotic deformity improved from 59.9° (45° to 110°) pre-operatively to 17.5° (3° to 40°) at a mean follow-up of 47.0 months (29 to 85). Spinal cord monitoring was used in all patients and there were no complications during surgery. These promising results indicate the possible advantages of the described technique over the established procedures. We believe that surgery should be performed in case of documented progression and before structural secondary curves develop. Our current strategy after documented progression is to recommend surgery at the age of five years and when 90% of the diameter of the spinal canal has already developed.

Cite this article: Bone Joint J 2013;95-B:1527–32.
Reverse shoulder replacement after resection of the proximal humerus for bone tumours
Authors: Kaa A. K. S. , Jørgensen P. H. , Søjbjerg J. O. , Johannsen H. V.
Published: October 2013

We investigated the functional outcome in patients who underwent reverse shoulder replacement (RSR) after removal of a tumour of the proximal humerus. A total of 16 patients (ten women and six men) underwent this procedure between 1998 and 2011 in our hospital. Five patients died and one was lost to follow-up. Ten patients were available for review at a mean follow-up of 46 months (12 to 136). Eight patients had a primary and two patients a secondary bone tumour.

At final follow up the mean range of active movement was: abduction 78° (30° to 150°); flexion 98° (45° to 180°); external rotation 32° (10° to 60°); internal rotation 51° (10° to 80°). The mean Musculoskeletal Tumor Society score was 77% (60% to 90%) and the mean Toronto Extremity Salvage Score was 70% (30% to 91%). Two patients had a superficial infection and one had a deep infection and underwent a two-stage revision procedure. In two patients there was loosening of the RSR; one dislocated twice. All patients had some degree of atrophy or pseudo-atrophy of the deltoid muscle.

Use of a RSR in patients with a tumour of the proximal humerus gives acceptable results.

Cite this article: Bone Joint J 2013;95-B:1551–5.
Effect of early administration of alendronate after surgery for distal radial fragility fracture on radiological fracture healing time
Authors: Uchiyama S. , Itsubo T. , Nakamura K. , Fujinaga Y. , Sato N. , Imaeda T. , Kadoya M. , Kato H.
Published: October 2013

This multicentre prospective clinical trial aimed to determine whether early administration of alendronate (ALN) delays fracture healing after surgical treatment of fractures of the distal radius. The study population comprised 80 patients (four men and 76 women) with a mean age of 70 years (52 to 86) with acute fragility fractures of the distal radius requiring open reduction and internal fixation with a volar locking plate and screws. Two groups of 40 patients each were randomly allocated either to receive once weekly oral ALN administration (35 mg) within a few days after surgery and continued for six months, or oral ALN administration delayed until four months after surgery. Postero-anterior and lateral radiographs of the affected wrist were taken monthly for six months after surgery. No differences between groups was observed with regard to gender (p = 1.0), age (p = 0.916), fracture classification (p = 0.274) or bone mineral density measured at the spine (p = 0.714). The radiographs were assessed by three independent assessors. There were no significant differences in the mean time to complete cortical bridging observed between the ALN group (3.5 months (se 0.16)) and the no-ALN group (3.1 months (se 0.15)) (p = 0.068). All the fractures healed in the both groups by the last follow-up. Improvement of the Quick-Disabilities of the Arm, Shoulder and Hand (QuickDASH) score, grip strength, wrist range of movement, and tenderness over the fracture site did not differ between the groups over the six-month period. Based on our results, early administration of ALN after surgery for distal radius fracture did not appear to delay fracture healing times either radiologically or clinically.

Cite this article: Bone Joint J 2013;95-B:1544–50.
Ponseti casting for club foot – above- or below-knee?
Authors: Maripuri S. N. , Gallacher P. D. , Bridgens J. , Kuiper J. H. , Kiely N. T.
Published: October 2013

We undertook a randomised clinical trial to compare treatment times and failure rates between above- and below-knee Ponseti casting groups. Eligible children with idiopathic clubfoot, treated using the Ponseti method, were randomised to either below- or above-knee plaster of Paris casting. Outcome measures were total treatment time and the occurrence of failure, defined as two slippages or a treatment time above eight weeks.

A total of 26 children (33 feet) were entered into the trial. The above-knee group comprised 17 feet in 13 children (ten boys and three girls, median age 13 days (1 to 40)) and the below-knee group comprised 16 feet in 13 children (ten boys and three girls, median age 13 days (5 to 20)). Because of six failures (37.5%) in the below-knee group, the trial was stopped early for ethical reasons. The rate of failure was significantly higher in the below-knee group (p = 0.039). The median treatment times of six weeks in the below-knee and four weeks in the above-knee group differed significantly (p = 0.01).

This study demonstrates that the use of a below-knee plaster of Paris cast in conjunction with the Ponseti technique leads to unacceptably high failure rates and significantly longer treatment times. Therefore, this technique is not recommended.

Cite this article: Bone Joint J 2013;95-B:1570–4.
A reliable measurement for identifying a lumbosacral transitional vertebra with a solid bony bridge on a single-slice midsagittal MRI or plain lateral radiograph
Authors: Farshad M. , Aichmair A. , Hughes A. P. , Herzog R. J. , Farshad-Amacker N. A.
Published: October 2013

The purpose of this study was to devise a simple but reliable radiological method of identifying a lumbosacral transitional vertebra (LSTV) with a solid bony bridge on sagittal MRI, which could then be applied to a lateral radiograph.

The vertical mid-vertebral angle (VMVA) and the vertical anterior vertebral angle (VAVA) of the three most caudal segments of the lumbar spine were measured on MRI and/or on a lateral radiograph in 92 patients with a LSTV and 94 controls, and the differences per segment (Diff-VMVA and Diff-VAVA) were calculated. The Diff-VMVA of the two most caudal vertebrae was significantly higher in the control group (25° (sd 8) than in patients with a LSTV (type 2a+b: 16° (sd 9), type 3a+b: -9° (sd 10), type 4: -5° (sd 7); p < 0.001). A Diff-VMVA of ≤ +10° identified a LSTV with a solid bony bridge (type 3+4) with a sensitivity of 100% and a specificity of 89% on MRI and a sensitivity of 94% and a specificity of 74% on a lateral radiograph. A sensitivity of 100% could be achieved with a cut-off value of 28° for the Diff-VAVA, but with a lower specificity (76%) on MRI than with Diff-VMVA.

Using this simple method (Diff-VMVA ≤ +10°), solid bony bridging of the posterior elements of a LSTV, and therefore the first adjacent mobile segment, can be easily identified without the need for additional imaging.

Cite this article: Bone Joint J 2013;95-B:1533–7.
Circulating Proteolytic Products of Carboxypeptidase N for Early Detection of Breast Cancer
Authors: Li Yaojun , Li Yueguo , Chen Tao , Kuklina Anna S , Bernard Paul , Esteva Francisco J , Shen Haifa , Ferrari Mauro , Hu Ye
Published: October 2013

BACKGROUND

Carboxypeptidase N (CPN) is important in regulating vasoactive peptide hormones, growth factors, and cytokines by specifically cleaving their C-terminal basic residues. We investigated whether circulating peptides specifically cleaved by CPN in the tumor microenvironment can be stage-specific indicators of breast cancer.

METHODS

CPN activity was measured using an ex vivo peptide cleavage assay by incubating synthesized C3f peptide (His6-C3f_S1304-R1320-His6) in interstitial fluids of breast tumors and adjacent normal breast tissues in mice with orthotopic implantation of the human cell line MDA-MB-231. The nature and extent of peptide cleavage by CPN was investigated by fragment profiling using nanopore fractionation and mass spectrometry. The fragment profiles in interstitial fluid correlated with concentrations of CPN-catalyzed peptides in blood samples taken from the tumor-bearing mice, healthy women, and breast cancer patients. CPN expression in the same set of samples was further examined by immunohistochemistry and immunoblotting.

RESULTS

We showed that generation of C3f_R1310-L1319 specifically correlated with the CPN expression level. In both the mouse and clinical patient samples, CPN was clearly increased in tumor tissues compared with normal breast tissue, whereas corresponding CPN abundance in blood remained constant. Concentrations of 6 CPN-catalyzed peptides predominantly increased in sera taken from the mice (n = 8) at 2 weeks after orthotopic implantation. Six homologous peptides displayed significantly higher expression in the patients' plasma as early as the first pathologic stage of breast cancer.

CONCLUSIONS

Circulating CPN-catalyzed peptide concentrations reflect the CPN activity in tumors. These biomarkers show strong potential for the noninvasive and early diagnosis of breast cancer.
Extensive study of human insulin immunoassays: promises and pitfalls for insulin analogue detection and quantification
Authors: Heurtault Béatrice , Reix Nathalie , Meyer Nicolas , Gasser Françoise , Wendling Marie-Josée , Ratomponirina Charline , Jeandidier Nathalie , Sapin Rémy , Agin Arnaud
Published: October 2013

Background: Over the last few decades, new synthetic insulin analogues have been developed. Their measurement is of prime importance in the investigation of hypoglycaemia, but their quantification is hampered by variable cross-reactivity with many insulin assays. For clinical analysis, it has now become essential to know the potential cross-reactivity of analogues of interest.

Methods: In this work, we performed an extensive study of insulin analogue cross-reactivity using numerous human insulin immunoassays. We investigated the cross-reactivity of five analogues (lispro, aspart, glulisine, glargine, detemir) and two glargine metabolites (M1 and M2) with 16 commercial human insulin immunoassays as a function of concentration.

Results: The cross-reactivity values for insulin analogues or glargine metabolites ranged from 0% to 264%. Four assays were more specific to human insulin, resulting in negligible cross-reactivity with the analogues. However, none of the 16 assays was completely free of cross-reactivity with analogues or metabolites. The results show that analogue cross-reactivity, which varies to a large degree, is far from negligible, and should not be overlooked in clinical investigations.

Conclusions: This study has established the cross-reactivity of five insulin analogues and two glargine metabolites using 16 immunoassays to facilitate the choice of the immunoassay(s) and to provide sensitive and specific analyses in clinical routine or investigation.
The Evaluation Criteria of Recruiting Local Staffs for Taiwanese Enterprise in China
Authors: Lu Shih-Tong , Lin Cheng-Wei , Dai Yuan-Fung , Shiue Yih-Chearng
Published: October 2013

Taiwanese enterprises are currently facing competitive challenges in both domestic and international markets as well as being under huge pressure from economic change. They must learn to intensely study this environment to find a suitable place for investment to extend their businesses. Usually, the first priority for an investment location is in mainland China, largely because of the closeness of culture and language, which make it easier to integrate resources between the headquarters in Taiwan and subsidiaries in China. The employment of suitable local staff members in China is very important to the success of business operations. This article reviews the literature related to multinational enterprise staffing selection and the factors that should be considered. These are then categorized into four dimensions and 20 sub-factors that can be used for the recruitment of local staff in China. The fuzzy linguistic preference relation (Fuzzy LinPreRa) approach is employed to assess the importance of these factors. The goal is to help managers reduce the risk of employing inappropriate local staff members and to enhance management effectiveness.
Six-year follow-up of a characteristic osteolytic lesion in a patient with tumor-induced osteomalacia
Authors: Piemonte Sara , Romagnoli Elisabetta , Cipriani Cristiana , De Lucia Federica , Pilotto Roberta , Diacinti Daniele , Pepe Jessica , Minisola Salvatore
Published: October 2013

Objective

Tumor-induced osteomalacia is a rare paraneoplastic syndrome characterized by hypophosphatemia and inappropriately normal or low 1,25-dihydroxyvitamin D.

Clinical case

Here, we report a 6-year postoperative follow-up of a patient with oncogenic osteomalacia with a distinctive skeletal manifestation. The latter was characterized by an almost linear lytic lesion of a few millimeters with irregular borders, mainly involving the trabecular compartment but extending into cortical shell, located in the middle third of the right fibula. Six years after tumor resection, a sclerotic repair with a complete recovery was observed. Furthermore, we monitored a striking increase in bone mineral density throughout the observation period, reaching a peak of 73% over basal values at lumbar spine after 2 years; at total femur and radius, the peak was 47.5 and 4.6% respectively, after 4 years from tumor resection.

Conclusions

We report for the first time that an osteolytic lesion may be part of the skeletal involvement in tumor-induced osteomalacia.