bluuebunny/crossref_metadata_2025 huggingface dataset:
Symmetric Encryption Algorithm Inspired by Randomness and Non-Linearity of Immune Systems
Authors: Ariffin Suriyani , Mahmod Ramlan , Jaafar Azmi , Ariffin Muhammad Rezal Kamel
Published: November 2012

In data encryption, the security of the algorithm is measured based on Shannon’s confusion and diffusion properties. This paper identifies the correspondences and highlights the essential computation elements on the basis of randomness and non-linearity of immune systems. These systems can be applied in symmetric encryption algorithm that satisfies the properties in designing a new symmetric encryption block cipher. The proposed symmetric encryption block cipher called the 3D-AES uses components of the Advanced Encryption Standard (AES) symmetric encryption block cipher and the new core components based on immune systems approaches. To ensure adequate high security of the systems in the world of information technology, the laboratory experiment results are presented and analyzed. They show that the randomness and non-linearity of the output in the 3D-AES symmetric encryption block cipher are comparable to the AES symmetric encryption block cipher.
Rough and Soft Set Approaches for Attributes Selection of Traditional Malay Musical Instrument Sounds Classification
Authors: Senan Norhalina , Ibrahim Rosziati , Nawi Nazri Mohd , Yanto Iwan Tri Riyadi , Herawan Tutut
Published: November 2012

Feature selection or attribute reduction is performed mainly to avoid the ‘curse of dimensionality’ in the large database problem including musical instrument sound classification. This problem deals with the irrelevant and redundant features. Rough set theory and soft set theory proposed by Pawlak and Molodtsov, respectively, are mathematical tools for dealing with the uncertain and imprecision data. Rough and soft set-based dimensionality reduction can be considered as machine learning approaches for feature selection. In this paper, the authors applied these approaches for data cleansing and feature selection technique of Traditional Malay musical instrument sound classification. The data cleansing technique is developed based on matrices computation of multi-soft sets while feature selection using maximum attributes dependency based on rough set theory. The modeling process comprises eight phases: data acquisition, sound editing, data representation, feature extraction, data discretization, data cleansing, feature selection, and feature validation via classification. The results show that the highest classification accuracy of 99.82% was achieved from the best 17 features with 1-NN classifier.
Accounts of infant-feeding advice received by mothers: Queensland, Australia, 1945-1965
Authors: Thorley Virginia
Published: November 2012

In the period 1945-1965 most women in the state of Queensland, Australia, gave birth in hospitals and thereafter they used a variety of services and individuals for advice on infant feeding. The services available were similar throughout the period. As mothers rarely worked outside the home, being good mothers was important to their identity. In this historical study, telephone interviews and written responses involving 44 mothers and former nurses from every region of this geographically vast state were used in order to investigate sources of personal advice on infant feeding used during this period, mothers’ experience relating to this advice, and the extent to which they followed the advice. The free, nurse-run well-baby clinics and related services conducted by the state’s Maternal and Child Welfare service were the most commonly mentioned services. However, the uptake of advice from this source showed considerable variation as women also drew upon family members, their general practitioners, advice columns, radio broadcasts, other mothers and their own judgment. Only rarely was a specialist pediatrician consulted. A minority of mothers was advised by pharmacists, private baby nurses, or entered residential mothercraft facilities. An important finding is that attendance at the baby clinics did not necessarily equate with compliance, especially as mothers became more experienced.
Mathematics teachers’ reflective practice within the context of adapted lesson study
Authors: Posthuma Barbara
Published: November 2012

There seems to be paucity of research in South Africa on mathematics teachers’ reflective practice. In order to study this phenomenon, the context of lesson study (in an adapted form) was introduced to five mathematics teachers in a rural school in the Free State. The purpose was to investigate their reflective practice whilst they collaboratively planned mathematics lessons and reflected on the teaching of the lessons. Data were obtained through interviews, video-recorded lesson observations, field notes taken during the lesson study group meetings and document analyses (lesson plans and reflective writings). The adapted lesson study context provided a safe space for teachers to reflect on their teaching and they reported an increase in self-knowledge and finding new ways of teaching mathematics to learners. This finding has some potential value for planning professional learning programmes in which teachers are encouraged to talk about their classroom experiences, share their joys and challenges with one another and strive to build a community of reflective practitioners to enhance their learners’ understanding of mathematics.
Is the Improved Efficacy of Trastuzumab and Lapatinib Combination Worth the Added Toxicity? A Discussion of Current Evidence, Recommendations, and Ethical Issues regarding Dual HER2-Targeted Therapy
Authors: Ahn Eugene R. , Wang Emilie , Glück Stefan
Published: November 2012

Following FDA approval of trastuzumab in 1998 and lapatinib in 2007, several clinical studies have addressed the question of whether trastuzumab and lapatinib combination therapy is better than trastuzumab alone in the metastatic breast cancer and neoadjuvant setting. In this review, updated to September 2012, we focus on the relevant clinical trials that address this question and, based on the available data, reach conclusions regarding a rational and reasonably individualized approach to the management of HER2+ breast cancer. With the FDA approval of pertuzumab in June 2012 and the likely approval of T-DM1 approaching, several ethical issues overshadow the excitement oncologists have for these new treatment options. We discuss the potential evolution of highly active anti-HER2 therapy (HAAHT) as an optimal treatment paradigm for HER2+ breast cancer. Additionally, we review lessons learned from the evolution of HAART for HIV treatment.
An Unusual Instrumentation-Related S1 Radiculopathy in a Patient Treated for a Primary Vertebral (L3) Lymphoma
Authors: Iacoangeli Maurizio , Di Rienzo Alessandro , Nocchi Niccolò , Alvaro Lorenzo , Gladi Maurizio , Colasanti Roberto , Herber Nathalie , Dobran Mauro , Scerrati Massimo
Published: November 2012

Paravertebral titanium rod migration represents an unusual and potentially fatal complication of vertebral stabilization surgical procedures. This condition, which requires a prompt and rapid diagnosis, is often mistaken for other more common diseases, or scotomized. We present a case of a 69 years old female affected by a non-Hodgkin lymphoma with evidence of migration of both rods five years after the posterior stabilization procedure for a pathological L3 fracture. Unusual clinical onset was represented by a left S1 radiculopathy without other symptoms. For several months, the symptoms were attributed to a possible radicular infiltration by the lymphoma. We conclude that paravertebral rod migration could happen not only within the spinal canal, but could also rarely damage blood vessels or parenchymal organs. This is generally a long-term complication, probably due to an insufficient fixation. Strict long-term follow-up monitoring is mandatory since this unusual complication can mimic other more common pathological conditions.
Albert Camus et Prométhée
Authors: Voisset-Veysseyre Cécile
Published: November 2012

Le mythe de Prométhée dit la rébellion comme commencement. Le Titan qui tint tête à Zeus et prit le feu pour le donner aux hommes est devenu modèle humain, figure d’un heureux esprit de révolte et symbole d’une foi en l’espèce humaine. C’est l’histoire d’un geste au beau milieu du désert où le héros est lié à un rocher pour être délié. Avec Albert Camus, Prométhée entre dans une histoire laïcisée de la création. “Qu’est-ce qu’un artiste ?” est la question de l’écrivain qui universalise un mythe grec et oriental ; le façonnage, empreinte titanesque de la créature, vaut comme un défi lancé au réel par l’art.
Intraoperative Prognostic Factors for Probing Outcome in Children with Congenital Nasolacrimal Duct Obstruction
Authors: Andalib Dima , Nabei Reza
Published: November 2012

Purpose

To evaluate the intraoperative prognostic factors for probing outcome in children with congenital nasolacrimal duct obstruction (CNLDO).

Methods

In a prospective interventional study, 69 eyes of 60 children aged 12 to 24 months with CNLDO underwent probing and irrigation. All procedures were performed by a single oculoplastic surgeon. The nature of the obstruction was classified by the surgeon as simple or complex. The fluency of irrigation after probing was defined as easy or difficult. Treatment success was defined as no epiphora or mucus discharge at 3 months after probing.

Results

The mean age at the time of probing was 15.3±3.1 months (range, 12–23 months). Treatment success was achieved in 56 of 69 eyes (81.2%). There was a significant difference in success rate of probing in eyes with simple obstruction (87.8%) compared with complex obstruction (65%) (p=0.02). Also, there was a significant difference in success rate of probing in eyes with easy irrigation (100%) compared with difficult irrigation (53.6%) (p<0.001).

Conclusions

Probing was more successful in eyes with simple obstruction or easy irrigation in children aged 12 to 24 months. The fluency of irrigation as an objective finding was a reliable intraoperative prognostic factor for probing success.
Light-Trap Catch of the Harmful Moths Depending of Moonlight in North Carolina and Nebraska States of USA
Authors: Nowinszky László , Puskás János
Published: November 2012

The present study discusses the light trapping of harmful insects depending on the moonlight, its polarized percentage, and the moon phases. The trapping data were taken from light traps of North Carolina and Nebraska States of USA. We examined five species. The maximum individual number of species was collected at new moon or near the first quarter and last quarter. The farmers can use our results to forecast their plant protecting works.
Basics Polyakov’s Quantum Surface Theory on the Formalism of Functional Integrals and Applications
Authors: Botelho Luiz C. L.
Published: November 2012

We propose an alternative view to the covariant Polyakov’s string path integral.
In our new approach we clarified the role of the Liouville model on string
theory for Q.C.D. and Dual Models. In the appendices, we present additional material,
difficult to find in the specialized path integral literature on the detailed evaluation of the
(Q.C.D.) fermion determinant, the path integral proof of the Atiyah-Singer index theorem
on Riemannian Manifolds, and the role of the expansion on Polyakov’s String path
integral, all containing important new results, insights on theses topics.
Ausência de estabilização da curva de acumulação de espécies em florestas tropicais
Authors: Schilling Ana Cristina , Batista João Luis Ferreira , Couto Hilton Zarate do
Published: November 2012

http://dx.doi.org/10.5902/198050985083A definição do tamanho da amostra é um dos principais problemas em levantamentos fitossociológicos. A curva de acumulação de espécies é comumente utilizada para definir a suficiência amostral, mas este método apresenta algumas limitações, como a ausência de um ponto de estabilização que possa ser determinado objetivamente e a arbitrariedade da ordem de entrada das unidades amostrais na construção da curva. Uma solução para esse problema é o uso de procedimentos de aleatorização, como a permutação, para obter curvas médias de acumulação de espécies e seus intervalos de confiança empíricos. Entretanto, esse procedimento enfatiza o caráter assintótico da curva, que não apresenta ponto de inflexão, tornando-se impossível a determinação de um ponto objetivo para avaliar o tamanho ótimo da amostra.
Zoomusicology and Ethnomusicology: A Marriage to Celebrate in Heaven
Authors: Keller Marcello Sorce
Published: November 2012

What Cartesian nonsense to think of birdsong as pre-programmed cries uttered by birds to advertise their presence to the opposite sex, and so forth! Each bird-cry is a full-hearted release of the self into the air, accompanied by such joy, as we can barely comprehend.

(J. M. Coetzee,Diary of a Bad Year, 2008:132)

S'il s'avère que la musique est un phénomène répandu chez plusieurs espèces vivantes en-dehors de l'homme, cela remettra forcément en cause la définition de la musique, et plus largement de l'homme et de sa culture, ainsi que l'idée que l'on se fait de l'animal lui-měme.

(François-Bernard Mâche,Musique, mythe, nature, 1983:61)
Considerations for the Management of Cryptotia Based on the Experience of 34 Patients
Authors: Kim Seok-Kwun , Yoon Chung-Min , Kim Myung-Hoon , Kim Min-Su , Lee Keun-Cheol
Published: November 2012

Background Cryptotia is a congenital ear deformity in which the upper pole appears buried beneath the mastoid skin. Cryptotia is a common auricular malformation among Asians. The aim of this paper is to examine the surgical techniques for and complications of 34 cryptotic patients.

Methods Surgery was performed for 34 cryptotic deformities (January 2005 to January 2012). Twenty-two patients (64.7%) were classified as having type I cryptotia, and 12 patients (37.5%) type II cryptotia. Among the type I cryptotia patients, 8 patients had mild deformity and 14 severe deformity. Among the type II cryptotia patients, 10 patients had mild deformity and 2 severe deformity.

Results The mild deformities were corrected via Z-plasty, V-Y plasty, full-thickness skin graft, and transposition flap, while the severe deformities were corrected via cartilage graft or Medporfor the spread of cartilage adhesion of antihelix. There were two cases of reinvagination in the autologous cartilage graft group. Implant exposure occurred with Medpor (two cases). There were two cases of hypertrophic scar on the previous surgical wound with Medpor. There were no complications in the 18 patients who had mild deformities.

Conclusions The type I cryptotia patients had more severe deformities than the type II cryptotia patients. As most of the type II cryptotia patients had only mild deformities, their deformities were corrected without using autologous conchal cartilage graft or Medpor, except for two patients. Through more case analyses, researchers should make an effort to identify methods for recurrence and prevention of complication.
The Usefulness of Nasal Packing with Vaseline Gauze and Airway Silicone Splint after Closed Reduction of Nasal Bone Fracture
Authors: Kim Hyo Young , Kim Sin Rak , Park Jin Hyung , Han Yea Sik
Published: November 2012

Background Packing after closed reduction of a nasal bone fracture causes inconvenient nasal obstruction in patients. We packed the superior meatus with Vaseline gauze to support the nasal bone, and packed the middle nasal meatus with a Doyle Combo Splint consisting of an airway tube, a silastic sheet, and an expandable sponge to reduce the inconvenience. In addition, we aimed to objectively identify whether this method not only enables nasal respiration but also sufficiently supports the reduced nasal bone.

Methods Nasal ventilation was measured via spirometry 1 day before surgery and compared to 1 day after surgery. To compare support of the reduced nasal bone by the 2 methods, 2 plastic surgeons assessed the displacementon X-rays taken after the surgery and after removing the packing. The extent of nasal obstruction, dry mouth, sleep disturbance, headache, and swallowing difficulty were compared with visual analog scales (VAS) on a pre-discharge survey.

Results In the experimental group, the nasal respiration volume 1 day after surgery remained at 71.3%±6.84% on average compared to 1 day prior to surgery. Support of the reduced bone in the experimental group (2.80±0.4) was not significantly different from the control group (2.88±0.33). The VAS scores for all survey items were lower in the experimental group than in the control group, where a lower score indicated a lower level of inconvenience.

Conclusions The nasal cavity packing described here maintained objective measures of nasal respiration and supported the reduced bone similar to conventional methods. Maintaining nasal respiration reduced the inconvenience to patients, which demonstrates that this packing method is useful.
Radical Surgical Excision and Use of Lateral Thoracic Flap for Intractable Axillary Hidradenitis Suppurativa
Authors: Teo Wan-Lin , Ong Yee-Siang , Tan Bien-Keem
Published: November 2012

Current treatments for hidradenitis suppurativa (HS) include prolonged courses of antibiotics, retinoids, immunosuppressants, and biologics. Severe cases that are resistant to prolonged medical treatment pose a therapeutic challenge. We propose radical excision and lateral thoracic flap reconstruction as a treatment option for such cases. In our experience with two patients, good aesthetic and functional outcomes were achieved, with a high level of patient satisfaction. The availability of suitable flap coverage allows for wide resection of all of the hair-bearing skin, leading to a low incidence of residual disease and subsequent recurrence. Following excision of the affected tissue, the ideal reconstructive method in the axilla provides suitable coverage without unacceptable donor site morbidity and also avoids axillary contractures. A long lateral thoracic flap with delay has excellent coverage with minimal donor tissue sacrifice. With a suitable flap coverage option, the management paradigm of intractable HS should shift from prolonged medical treatment to allow decisive radical excision, which will improve the quality of life for patients.
The NRTI BMS‐986001 does not degrade mitochondrial DNA in long‐term primary cultures of cells isolated from human kidney, muscle and subcutaneous fat
Authors: Wang F , Flint O
Published: November 2012

Background

Nucleoside reverse transcriptase inhibitors (NRTIs) are often used in the treatment of HIV infections, although their use has been in some cases been limited by adverse side effects attributed to inhibition of eukaryotic mitochondrial DNA polymerase gamma (mtDNA polγ). The primary objective of this study was to compare the in vitro toxicity of the novel HIV thymidine‐analogue NRTI, BMS‐986001 (OBP‐601) to that of five other NRTIs: tenofovir (TFV), adefovir (ADV), azidothymidine (AZT), stavudine (D4T), and abacavir (ABC).

Methods

Primary cultures of human renal proximal tubule epithelium, muscle, preadipocytes and differentiated adipocytes (subcutaneous) were exposed to each of the NRTIs at their reported Cmax concentration and at 200 M for 5, 10, 14 and 19 days. Six in vitro cytotoxicity parameters were measured: percent dead cells, cell protein and ATP content, lactate concentration in the media, and mtDNA (ATP8) content by qPCR. Results were analyzed by analysis of variance followed by Dunnet's post hoc test.

Results

BMS‐986001 was not cytotoxic in any of the 4 cell culture systems tested. TFV was cytotoxic in muscle cells and preadipocytes with regard to mtDNA content which decreased in a concentration‐ and time‐dependent manner to approximately 40% control values. In contrast, ADV, AZT and d4T were cytotoxic in all 4 cell culture systems and with regard to all measured parameters. ABC was only significantly cytotoxic at the higher concentration (200 M) tested.

Conclusions

Based on in vitro assessments, when compared to five other NRTIs (TFV, ADV, AZT, d4T and ABC) in primary cultures of human cells, BMS‐986001 was the least cytotoxic. The most cytotoxic were ADV, AZT, and d4T. In spite of their very close structural similarity, the relative lack of toxicity of BMS‐986001 compared to d4T is consistent with the 100‐fold greater potency of d4T for inhibition of mtDNA polγ.
Prevalence of vitamin D deficiency in human immunodeficiency virus‐infected patients
Authors: Fridman V , Bello N , Godoy E , Stecher D , Lasala M
Published: November 2012

Purpose of the study

Vitamin D deficiency in the adults could produce osteomalacia, secondary hyperparathyroidism with bone loss and increased risk of fractures. An increased prevalence of osteopenia, osteoporosis, decreased bone density, vitamin D deficiency and increased risk of fracture was found in HIV‐positive patients. A study performed in Buenos Aires, Argentina that included non‐HIV‐infected adult patients showed 15% prevalence of vitamin D deficiency in winter and 0% prevalence in summer. There is no local data published of vitamin D deficiency in HIV‐positive populations. The aim of the study is to determinate the prevalence of vitamin deficiency in our HIV‐positive population receiving HAART.

Methods

An observational, retrospective study was performed. We reviewed the clinical charts of the HIV‐positive adult patients attending the infectious disease clinic. We collected data of vitamin D, parathormone and beta cross laps value; we recorded if the test was performed in winter or summer. We considered vitamin D deficiency if<10 ng/ml. We recorded age, sex, comorbidities (diabetes mellitus, renal failure, hepatic failure, HBV and/or HCV coinfection, menopause, malignancy and metabolic syndrome), months since HIV diagnosis, CD4 count, viral load and HAART.

Summary of results

60 patients were included, 49 (65%) of whom were male. Mean age was 49.15 years. Mean time from diagnosis was 112 months. Mean CD4 count was 548 cells/mm3 and 6.6% presented CD4 <200; 83.3% had viral load <50 copies/mm3. All patients were on HAART; 50% received efavirenz, 65% received tenofovir and 11.6% recived atazanavir. Mean vitamin D value was 23.58 ng/ml (5–66.5 ng/ml). In winter, 15.3% of the patients had <10 ng/ml of vitamin D and mean value was 24.16 ng/ml (10–40 ng/ml). Although the mean value in summer was 25.8 ng/ml (11.6–66 ng/ml) 10% of the patients had vitamin D deficiency. PTH value was abnormal in 31.6% of patients and beta cross laps was abnormal in 10% of patients.

Conclusions

Although the small number of patient included, we observed a high prevalence of vitamin D deficiency even in summer. A systematic assessment of vitamin D must be included in HIV positive patient care.
Effect of food on the pharmacokinetics of emtricitabine/rilpivirine/tenofovir disoproxil fumarate single‐tablet regimen
Authors: Ramanathan S , Custodio J , Yin X , Hepner M , Pugatch D , Kearney B
Published: November 2012

Purpose

Emtricitabine/rilpivirine/tenofovir disoproxil fumarate (FTC/RPV/TDF; Complera®/Eviplera®) is a recently approved complete single tablet regimen (STR) for treatment‐naïve HIV‐1‐infected patients. Exposures of rilpivirine single agent Edurant®) are 40% lower when administered under fasted conditions versus standard meal (533 kcal) or high‐fat/high caloric meal (928 kcal). The present study evaluated the effect of standard and light meal on FTC/RPV/TDF pharmacokinetics (PK).

Methods

This was a three‐period, six‐sequence, crossover single‐dose study (N = 24) in healthy subjects that received FTC/RPV/TDF with a standard meal (540 kcal, 21 g fat), light meal (390 kcal, 12 g fat) or under fasted conditions (each treatment 18 days apart). Blood sampling was done for 192 hrs and PK of RPV, FTC, and tenofovir (TFV) were evaluated. Safety was monitored throughout the study and at 14‐day follow‐up. Exposures of study drugs from the various treatments were compared to fasted or standard meal as reference using 90% confidence interval (CI) bounds of 80 to 125% about the geometric mean ratio (GMR).

Results

Of the 24 enrolled subjects, 23 completed. There were no Grade 3 or 4 adverse events (AEs), serious AEs, or AEs leading to discontinuation. Compared to fasting conditions, RPV AUCinf was 9% and 16% higher with a light meal or standard meal, respectively. Compared to standard meal, RPV AUCinf was 14% and 6% lower with fasted or light meal administration, respectively. TFV and FTC exposures were consistent with their established PK/food effect (Table 1).

Exposure versus standard meal

GMR (%) 90% CI fasted/standard
GMR (%) 90% CI light meal/standard

Rilpivirine

AUCinf (ng*h/mL)
85.9 (72.7, 101)
93.8 (79.2, 111)

AUClast (ng*h/mL)
83.7 (70.6, 99.3)
94.9 (79.9, 113)

Cmax (ng/mL)
79.1 (65.5, 95.5)
106 (87.6, 129)

Emtricitabine

AUCinf (ng*h/mL)
105 (102, 108)
101 (98.2, 104)

AUClast (ng*h/mL)
105 (102, 108)
101 (98.2, 104)

Cmax (ng/mL)
107 (101, 114)
103 (96.2, 109)

Tenofovir

AUCinf (ng*h/mL)
72.5 (68.1, 77.2)
93.0 (87.2, 99.2)

AUClast (ng*h/mL)
70.9 (66.3, 75.8)
92.8 (86.7, 99.4)

Cmax (ng/mL)
75.8 (67.8, 84.6)
84.8 (75.8, 94.9)

Conclusion

Administration with food has a modest effect on RPV PK as FTC/RPV/TDF STR versus fasted dosing, with no relevant differences between a light meal versus standard meal. FTC/RPV/TDF STR can be administered with a light or standard meal.
Prediction of drug‐drug interactions between various antidepressants and ritonavir using a physiologically based pharmacokinetic model
Authors: Siccardi M , Marzolini C , Seden K , Almond L , Kirov A , Khoo S , Owen A , Back D
Published: November 2012

Depression can impact on the treatment of HIV infection, and effective treatment of depressive conditions can have a beneficial effect improving adherence. However antidepressant treatment requires long‐term maintenance, and is prone to pharmacokinetic drug‐drug interactions (DDI) with antiretrovirals. The aim of this study was to predict the magnitude of DDI between ritonavir (RTV) and the most commonly prescribed antidepressants using a physiologically based pharmacokinetic (PBPK) model simulating virtual clinical trials. In vitro data describing the physiochemical properties, absorption, metabolism, induction and inhibitory potential of RTV and five antidepressants were obtained from published literature. Interactions between RTV and antidepressants were evaluated using the full PBPK model implemented in the Simcyp Population‐based Simulator (Version 11.1, Simcyp Limited, UK) and virtual clinical studies were simulated on 50 Caucasian subjects receiving 100mg bid of RTV for 21 days plus sertraline (100mg qd), citalopram (40mg qd), fluoxetine (20mg qd), venlafaxine (25mg qd) and then from day 14–21. Simulated pharmacokinetic parameters were compared with observed values available in the literature. The simulated PK parameters of RTV, sertraline, citalopram, fluoxetine, mirtazepine and venlafaxine given alone at standard dosage were similar to reference values obtain from published clinical studies. The effect of simulated RTV co‐administration on sertaline, fluoxetine and venlaflaxine was an AUC decrease of 40%, 26% and 6%, respectively and on mirtazepine and citalopram, an AUC increase of 60% and 20% respectively. The magnitude of the simulated DDI between RTV and the antidepressants was overall weak to moderate according to the classification of the FDA. The modest magnitude of these drug‐drug interactions could be explained by the fact that antidepressants are substrates of multiple isoforms thus metabolism can still occur through CYPs that are not or weakly impacted by RTV. Although from a pharmacokinetic point of view, venlafaxine or citalopram represent better candidates for patients on RTV, there are many considerations in seeking to optimize antidepressant therapy. The next stage in this work is to simulate DDI between boosted protease inhibitors and antidepressants. IVIVE is a useful tool for both prediction of drug‐drug interactions and design of prospective clinical trials, simulating optimal sample size, and selection of doses.
Darunavir plasma level in HIV overweight patients
Authors: Poupard M , Boussairi A , Krause J , Khuong‐Josses M
Published: November 2012

Purpose of the study

Darunavir (DRV) boosted with ritonavir is now regularly used in HIV infection. With an increasing population of HIV‐infected patients receiving antiretroviral therapy and having overweight problems we decided to conduct a transversal study on DRV plasma concentration in overweight patients.

Methods

Measures of drug plasma level were proposed to all patients having their routine blood test between 2010 and 2011 in our outpatient HIV clinic. With their consent they were included in our transversal study. DRV plasma concentrations (C12 h=12±3 hours) were determined using HPLC coupled with photodiode array detection (limit of quantification 0.05 mg/L), with DRV C12 h=1.3 mg/L and 0.55 (IC50) as target levels. Weight and height were also measured to calculate body mass index (BMI).

Results

We included 52 patients; 35 women and 17 men, mean age was 40 (±8.8). Majority of them (62%) were African patients. The median CD4 cell count was: 387 [297–551]. The viral load was<35 copies for 77% of the patients. We had 28 overweight patients: 12 patients had BMI ≥30 and 16 patients had BMI between 25 and 29; 87% of the patients had DRV/RTV 800/100 OAD regimen associated with tenofovir/emtricitabine (72%) or abacavir/lamivudine (17%). The mean DRV plasma trough concentrations (C12 h) according BMI are shown in Table 1. Six patients with BMI ≥25 had a low plasma concentration of DRV with OAD regimen of DRV/RTV 800/100: 2 in BMI 25–29 group and 4 in BMI≥30 group. Among the six patients no adherence issues was recorded and every patient had undetectable viral load. Only one patient has a C12 h lower than the IC50 from the DRV (0.55 mg/L) and 3 others have very probably Cmin close to the ECC50.

Body Mass Index
<25
25–29
≥30

Number of patients (n)
24
16
12

DRV plasma concentration (mg/L), Means±SD
3.54±1.60
3.07±1.57
2.58±1.62

Patients with [DRV] C12 h <1.3 mg/L (n)
0
2
4

Patients with [DRV] C12 h <0.55 mg/L (n)
0
0
1

Conclusion

Our results show a possible lower plasma concentration of DRV in overweight/obese patients in a small cohort. In our data, this reduced plasma concentration is not related to detectable viral load, possibly due to ICmin of DRV. More studies are needed to manage carefully antiretroviral therapy in overweight patients.
Moderator effect of CYP2B6 genotype in HIV‐1 patients with tuberculosis treated with rifampicin and efavirenz
Authors: De la Calle C , Sánchez A , Cordero M , Iglesias A , Luna G
Published: November 2012

Efavirenz (EFV) is the preferred non‐nucleoside reverse transcriptase inhibitor component of the ARV regimen in HIV‐TB patients. Concomitant use of EFV with rifampicin (RIF), an important component of first‐line tuberculosis treatment, induces various hepatic cytochrome P450 enzymes and is known to decrease EFV plasma concentrations in healthy volunteers and HIV‐1 patients and EFV plasma concentrations below 1,000 µg/mL have been associated with an increased risk of virological failure [1]. Moreover, previous studies have shown that inter‐individual variability in EFV plasma concentrations are associated with the presence of allelic variants in CYP2B6 gene. Carriers of the T allele of polymorphism 516 G>T are reported to be associated with slower EFV oral clearance. The aim of our study was to determine the influence of CYP2B6 genotype in EFV levels in HIV patients with TB treated with RIF. Four HIV patients who started ARV treatment concomitantly with TB treatment were analyzed. These patients started a regimen based on EFV at doses higher than standard due to RIF interaction. Viral load, CD4+ cell count and plasma levels of EFV in plasma were measured at each visit, and genotyping for CYP2B6 (516G>T) polymorphism were performed. The self‐reported rates of adherence to HAART were very high. One patient, who had TT genotype, required progressive dose reduction by toxic levels (Cmin: 20 µg/mL) and effects on the central nervous system. Dose was adjusted to 600 mg qd despite treatment with RIF, and he required even lower doses after completion of TB treatment, 400 mg qd. Two other patients with non‐mutated genotype (GG) required dose escalation up to 1000 mg qd to achieve minimum recommended EFV concentrations between 1 and 4 µg/mL. All of them achieved virological suppression at six months. The fourth patient, who had non‐mutated genotype, required dose increases for several months until dose adjustment. He needed 1600 mg qd during treatment with RIF. He presented virological failure, likely to maintain infratherapeutic levels of EFV for several months. Our study shows that the variability in EFV pharmacokinetic behaviour justifies the use of therapeutic drug monitoring (TDM) in situations in which there are potential interactions with other drug. Also, it is recommended to know CYP2B6 genotype in patients receiving HIV‐TB to predict their metabolizing behaviour. TDM in clinical practise continues to be the best tool for optimizing the dosing of EFV.
A randomized controlled trial of a web‐based psychological intervention for patients under treatment for chronic HIV infection
Authors: Skeie L , Drozd F , Kraft P , Kvale D
Published: November 2012

Purpose of the study

One of the most prevalent mental conditions in people with HIV is depression as uniquely characterized by low positive affect. This study examined the effect of a web‐based intervention (Avanti) on overall mood and depressive symptoms among patients with HIV infection.

Methods

Patients treated with effective antiretroviral treatment were included in a two‐armed trial with substance abuse as an exclusion criterion and randomized to Avanti (n=36) or control (n=31). Patients were surveyed at baseline, as well as 1 and 3 months after the initiation of a 5‐week intervention period. Outcomes were Center for Epidemiological Studies‐Depression scale and the Positive and Negative Affect Schedule which was combined into an overall mood index. Changes within groups were tested by Wilcoxon matched pairs test and baseline differences between groups by chi‐square and Mann‐Whitney independent samples test.

Summary of results

Baseline scores for both groups were similar. However, patients in the intervention group had an improvement in median (M) overall mood from baseline (M=67.6) to 1 month (M=71, p=0.02) which was also maintained from 1 to 3 months (M=71.9). Moreover, these patients had a favorable reduction in negative affect from 1 (M=24) to 3 months (M=22, p=0.01) and a transient improvement in positive affect from baseline (M=31.7) to 1 month after intervention onset (M=35, p<0.01) which almost returned to baseline levels at month 3 (M=32, p=0.01). In contrast, no significant changes were observed within the control group, except for a reduction in negative affect from 1 (M=23) to 3 months (M=21.6, p=0.05). Notably, symptoms of depression at baseline were low in both the Avanti (M=13) and control (M=12) groups, possibly explaining why no further reduction in depression was observed from baseline to 3 months in either of the two groups.

Conclusions

The results of this study lend support to the promise of a web‐based psychological intervention among patients with HIV and its ability to improve overall mood with favorable intervention‐related changes in negative and positive affect. Avanti had no effect on depression but this was probably due to low initial symptoms of depression. The findings suggest that a prolonged web‐based intervention with regular contact could maintain the positive effects on mood seen in this study. If so, Avanti could potentially provide an easily accessible and cost‐effective adjunct to traditional psychotherapy.
When doctors come to prison – a pilot project for better HIV care in correctional facilities
Authors: Vaz Pinto I , Santos C , Soares C , Vera J
Published: November 2012

Recent rearrangements in national policies regarding follow‐up of HIV‐infected inmates have determined that hospitals closest to the prison facility be responsible for their care. Our HIV Unit and the two prison facilities in the area have established a clinical protocol whereby a clinical team goes to the prisons for blood collecting and visits instead of having the inmates transported to the hospital. The purpose of the protocol, from a clinical point of view, was to: (i) promote adherence to blood tests and clinical visits; (ii) promote adherence to antiretroviral (ARV) therapy; (iii) facilitate ARV administration by promoting once‐daily‐dosing. This retrospective review looks back at the first year of protocol implementation between the HIV Unit of HPP Cascais Hospital and the prisons of Tires and Linhó. The purpose of this study is to characterize the demographics of our inmate population; assess the number of inmates on ARV and describe the regimens as PI‐ or NNRTI‐based and as once‐ or twice‐daily dosed; evaluate ARV efficacy by HIV viral load undetectability; and assess opportunity for ARV switch from twice‐ to once‐daily dosing. From April 2011 until June 2012 a total of 53 inmates were included in this protocol. The majority of patients were female (55%) as one of the prisons is mainly for female inmates. The median age is 36 years (from 23–59). The average time of follow‐up was 11 months (15 months maximum). From the total of 53 patients under study, 40 are currently under care, the other 13 having been released or transferred to other prison facilities. The majority of these patients are on ARV therapy (83%). By the end of follow‐up time 88% of patients were on a once‐daily dosed regimen; these are PI‐based in 69% and NNRTI‐based in 31%. At their last evaluation, 32/33 patients on therapy had undetectable HIV viremia (97%). As a conclusion, we assess that this protocol implementation has benefitted all parts: patients assure regular laboratory and clinical follow‐up, and avoid constraintful displacements to the hospital; prisons guarantee regular specialized medical assistance to inmates and save on multiple trips to the hospital; finally, the clinical team is rewarded with 100% adherence to visits and therapy, which is evident by 97% viral load undetectability. The major constraint found in this protocol was the difficulty in providing adequate discharge planning and linkage to care in the community due to frequent unannounced release of inmates.
Preparation and Extraction of Insoluble (Inclusion‐Body) Proteins from Escherichia coli
Authors: Palmer Ira , Wingfield Paul T.
Published: November 2012

High‐level expression of many recombinant proteins in Escherichia coli leads to the formation of highly aggregated protein commonly referred to as inclusion bodies. Inclusion bodies are normally formed in the cytoplasm; however, if a secretion vector is used, they can form in the periplasmic space. Inclusion bodies can be recovered from cell lysates by low‐speed centrifugation. Following pre‐extaction (or washing), protein is extracted from washed pellets using guanidine⋅HCl. The solubilized and unfolded protein is either directly folded or further purified by gel filtration in the presence of guanidine⋅HCl as described in this unit. A support protocol describes the removal of guanidine⋅HCl from column fractions so they can be monitored by SDS‐PAGE. Curr. Protoc. Protein Sci. 70:6.3.1‐6.3.20. © 2012 by John Wiley & Sons, Inc.
Serum‐Free Generation of Multipotent Mesoderm (Kdr+) Progenitor Cells in Mouse Embryonic Stem Cells for Functional Genomics Screening
Authors: McKeithan Wesley L. , Colas Alexandre R. , Bushway Paul J. , Ray Saugata , Mercola Mark
Published: November 2012

This unit describes a robust protocol for producing multipotent Kdr‐expressing mesoderm progenitor cells in serum‐free conditions, and for functional genomics screening using these cells. Kdr‐positive cells are able to differentiate into a wide array of mesodermal derivatives, including vascular endothelial cells, cardiomyocytes, hematopoietic progenitors, and smooth muscle cells. The efficient generation of such progenitor cells is of particular interest because it permits subsequent steps in cardiovascular development to be analyzed in detail, including deciphering the mechanisms that direct differentiation. In addition, the oligonucleotide transfection protocol used to functionally screen siRNA and miRNA libraries is a powerful tool to reveal networks of genes, signaling proteins, and miRNAs that control the diversification of cardiovascular lineages from multipotent progenitors. Technical limitations, troubleshooting, and potential applications of these methods are discussed. Curr. Protoc. Stem Cell Biol. 23:1F.13.1‐1F.13.13. © 2012 by John Wiley & Sons, Inc.
Elections, Roman
Authors: Yakobson Alexander
Published: November 2012

Publius Scipio Nasica was an illustrious and powerful statesman, who took pride in being leader of the Senate for many years. As a young man, when he was campaigning for the curule aedileship, he shook the hand of a peasant somewhat assiduously, as candidates are wont to do. He noticed that the man's hand is hardened by his rustic work, and jokingly asked him whether he was in the habit of walking on his hands. This saying, to which the bystanders took exception, spread among the people and was the cause of Scipio's defeat in the election. All the rural tribes thought that he was casting a slur on their poverty, and turned their anger against his offensive urbanity (Val. Max. 7.5.2).
Characterization and Simulation of Tensile Deformation of Non‐Uniform Cellular Aluminium Until Damage
Authors: Foroughi Babak , Degischer H. Peter , Kottar Andreas
Published: November 2012

The uniaxial tensile modulus and strength of Alulight® foams are measured and simulated taking into account the non‐uniform mass density distribution characterized non‐destructively by X‐ray computer tomography. The density mapping method is employed for the reconstruction of the hard and soft regions in the samples investigated. A finite element (FE)‐model is introduced for simulations of the deformation of a continuum composed by domains of different local densities. Existing constitutive laws for cellular structures are incorporated for the numerical simulation of tensile deformation and the variance of the material parameters is determined with the aid of a scaling relationship. The experimental results for the stiffness, the ultimate strength, and the corresponding strain agree with the developed 3D FE simulations and are compared with the estimations according to scaling laws for uniform cellular structures. The non‐uniformity of the material distribution affects the strength and the ductility significantly. Simulations taking this into account provide conservative property predictions. The calculated positions of local strain concentration correspond with the observed locations of crack initiation. The material modelling and the simulation of the elasto‐plastic deformation up to damage are suggested for application to macroscopic components made of non‐uniform cellular metals.
Microstructure and Nanoindentation Properties of Surface Textures Obtained by Laser Machining and Molding in Silicon Carbide
Authors: Valentini Francesco , Zambotto Italo , Sciti Diletta , Silvestroni Laura , Melandri Cesare , Guicciardi Stefano
Published: November 2012

A surface texture consisting of an array of holes in SiC components was obtained by either conventional molding in the green state or post sintering laser machining. According to microstructural analysis, very regular holes were obtained by laser machining with minimal microstructural damage. Irregular holes with defects and voids were instead found for the surface textures obtained via molding. Nanoindentation tests were performed in the areas close to the holes and no significant alteration of the mechanical properties was found after laser machining.
Reversible Amorphous‐to‐Amorphous Transitions in Chalcogenide Films: Correlating Changes in Structure and Optical Properties
Authors: Kalyva Maria , Orava Jiri , Siokou Angeliki , Pavlista Martin , Wagner Tomas , Yannopoulos Spyros N.
Published: November 2012

Structural transitions in materials are accompanied by appreciable and exploitable changes in physical‐chemical properties. Whereas reversible optically‐driven atomistic changes in crystal‐to‐amorphous transitions are generally known and exploited in applications, the nature of the corresponding polyamorphic transitions between two structurally distinct meta‐stable amorphous phases is an unexplored theme. Direct experimental evidence is reported for the nature of the atomistic changes during fully reversible amorphous‐to‐amorphous switching between two individual states in the non‐crystalline As50Se50 films prepared by pulsed‐laser deposition and consequent changes in optical properties. Combination of surface sensitive X‐ray photoelectron spectroscopy and spectroscopic ellipsometry show that the near‐bandgap energy illumination and annealing induce reversible switching in the material's structure by local bonding rearrangements. This is accompanied by switching in refractive index between two well‐defined states. Exploiting the pluralism of distinct structural states in a disordered solid can provide new insights into the data storage in emerging optical memory and photonic applications.
Mosaic 18q21.2 deletions including the TCF4 gene: A clinical report
Authors: Rossi Massimiliano , Labalme Audrey , Cordier Marie‐Pierre , Till Marianne , Blanchard Gaëlle , Dubois Remi , Guibaud Laurent , Heissat Sophie , Javouhey Etienne , Lachaux Alain , Mure Pierre‐Yves , Ville Dorothée , Edery Patrick , Sanlaville Damien
Published: November 2012

Pitt–Hopkins syndrome (PTHS) is characterized by distinctive facial dysmorphism, profound intellectual disability, and the possible occurrence of epilepsy and breathing anomalies. It is caused by haploinsufficiency of the TCF4 gene. No significant difference in clinical severity has been reported to date between PTHS patients carrying 18q21 deletions including the TCF4 gene, and those harboring TCF4 point mutations, suggesting a lack of genotype/phenotype correlation. Moreover, the size of 18q21 deletions including the TCF4 gene does not appear to have a significant effect on the phenotypic severity, suggesting that TCF4 haploinsufficiency is the most important prognostic factor in 18q deletions. We describe two unrelated patients presenting with clinical features reminiscent of PTHS and carrying mosaic interstitial 18q21 deletions characterized by array comparative genomic hybridization. One of the patients presented the lowest level of mosaic 18q21 deletion reported to date (5–10%). Our report and a review of the literature show that the mosaic status does not appear to have a significant effect on the clinical severity of 18q21 deletions, which are associated with a poor neurological outcome, whereas a mosaic TCF4 point mutation can result in a significantly milder phenotype. Malformations of internal organs are currently considered to be rare in PTHS. The patients described here had visceral anomalies, suggesting that a full morphological assessment, including heart and abdominal ultrasound scans, should be performed systematically in PTHS patients. © 2012 Wiley Periodicals, Inc.