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Background Supportive care is the cornerstone of management of adult and paediatric Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN). However, consensus on the modalities of supportive care is lacking.Objectives Our aim in this international multicentric Delphi exercise was to establish a multidisciplinary expert consensus to standardize recommendations regarding supportive care in the acute phase of SJS/TEN.Methods Participants were sent a survey via the online tool SurveyMonkey, consisting of 103 statements organized into 11 topics: multidisciplinary team composition, suspect drug management, infection prevention, fluid resuscitation and prevention of hypothermia, nutritional support, pain and psychological distress management, management of acute respiratory failure, local skincare, ophthalmological management, management of other mucosa, and additional measures. Participants evaluated the level of appropriateness of each statement on a scale of 1 (extremely inappropriate) to 9 (extremely appropriate). The results were analysed according to the RAND/UCLA Appropriateness Method.Results Forty-five participants from 13 countries (on three continents) participated. After the first round, a consensus was obtained for 82.5% of the 103 initially proposed statements. After the second round, a final consensus was obtained for 102 statements.Conclusions We have reached an international Delphi-based consensus on best supportive care practice for SJS/TEN. Our expert consensus should help guide physicians in treating patients with SJS/TEN and thereby improve short-term prognosis and the risk of sequelae.

A confined-doped ytterbium gain fiber was tested in a tandem-pump fiber amplifier. The fiber achieved an output power of 4.1kW and M2=1.59, with optical efficiency of 84% and no sign of rollover at maximum power.

Ytterbium-doped fiber lasers (YDFLs) operating at 1018nm have attracted much interest in recent years due to its application as a high brightness, low quantum defect pump source for multi-kilowatt fiber lasers. In addition to the main challenge of suppressing amplified spontaneous emission (ASE) occurring around 1030nm–1040nm as reported by various groups [1, 2], we find that accounting for the thermal sensitivity in the 1018nm laser design is also critical to power scaling.

The most common cause of dental crowding is the presence of an arch-length--tooth-size discrepancy. Conventional methods of gaining space in orthodontics involve the extraction of teeth, often premolars. However, there are a number of clinical situations in which the extraction of permanent molars might be considered. This paper highlights the indications, advantages, disadvantages and timing of the extraction of the first, second and third permanent molars in the treatment of a crowded malocclusion.

Metal bonding is an attractive solution for vertical interconnection formation in three dimension (3D) integration of microelectronic device. Cu-Cu direct "fusion" bonding is able to form vertical interconnection and provides great advantages compared to thermo-compression metal to metal bonding. It requires no heating and short period of time during the bonding process. Hydrophilic Cu metal films surface is achieved with Ar / N 2 plasma activation. Room temperature fusion bonding is performed on blanket wafers with the activated Cu films at atmospheric pressure and ambient air, followed by annealing at 300 °C. C-mode scanning acoustic microscopy (C-SAM) is performed on the bonded wafer. Transmission electron microscopy (TEM) and electron energy loss spectroscopy (EELS) are performed on the bonded sample. Zigzag bonding interface is observed and N 2 is not present at the bonding interface.

CMOS readout circuit is stacked on MEMS accelerometer using face-to-face (F2F) direct metal bonding. F2F bonding provides smaller form factor, latency, and power consumption. The CMOS chip acts as an active cap that encapsulates and provides interconnect routing to the MEMS chip. Metal bonding (Al-Au) was achieved at 300°C/10min/50N. The bond quality meets the requirements during shear and helium leak tests. The stacked CMOS/MEMS chip is verified to be functional and sustains shock test of 500g.

BackgroundPruritic papular eruption (PPE) of HIV is common in HIV-infected populations living in the tropics. Its aetiology has been attributed to insect bite reactions and it is reported to improve with antiretroviral therapy (ART). Its presence after at least 6months of ART has been proposed as one of several markers of treatment failure.ObjectivesTo determine factors associated with PPE in HIV-infected persons receiving ART.MethodsA case-control study nested within a 500-person cohort from a teaching hospital in Mbarara, Uganda. Forty-five cases and 90 controls were enrolled. Cases had received ART for ≥15months and had an itchy papular rash for at least 1month with microscopic correlation by skin biopsy. Each case was individually matched with two controls for age, sex and ART duration.ResultsTwenty-five of 45 cases (56%) had microscopic findings consistent with PPE. At skin examination and biopsy (study enrolment), a similar proportion of PPE cases and matched controls had plasma HIV RNA&nbsp

3D integration has been widely recognized as the next generation of technology for integrated microsystems with small form factor, high bandwidth, low power consumption, and possibility of heterogeneous More-than-Moore integration. Heterogeneous integration of MEMS and CMOS is critical in future development of multi-sensor data fusion in a low-cost chip size system. MEMS/CMOS integration was primarily done using monolithic and hybrid/package approaches until recently. In this work, 3D CMOS-on-MEMS stacking without TSV using direct (i.e. solder-less) metal bonding is demonstrated. This MEMS/CMOS integration leads to a simultaneous formation of electrical, mechanical, and hermetic bonds, eliminates chip-to-chip wire-bonding, and hence presents competitive advantages over hybrid or monolithic solutions. We present the fabrication flow and verify the performance of the stacked MEMS/CMOS microsystem in this paper. The micro-electro-mechanical system (MEMS) accelerometer is fabricated using bulk micromachining technology with silicon-on-insulator (SOI) substrate. The CMOS readout circuit for the capacitive MEMS accelerometer, implemented in 0.35 μm (2P4M) process, consists of three essential circuit blocks: (i) low noise, bandpass gain stage, (ii) synchronous demodulator and (iii) offchip, low-pass filter. The MEMS chip is metallized with a single layer of Au for electrical contact and sealing ring prior to bulk etching and release. Au is chosen to withstand harsh process conditions. The CMOS chip contains four Al metal layers. The top most layer is patterned for electrical contact and sealing ring that match those of the MEMS chip. In order to ensure proper operation, the delicate micro-structures (MEMS) should be protected from the ambient. In this approach, a hermetic seal ring is formed simultaneously during face-to-face stacking of CMOS on MEMS and hence eliminating the need for post-processing hermetic encapsulation. Face-to-face stacking also eliminates the need for chip-to-chip wire bonding. Effectively, the CMOS layer acts as an “active cap”. In addition, I/Os to the MEMS chip are routed through the CMOS metal layers to simplify the MEMS process. Since the I/O count is low, TSV is not used and electrical feed-through is achieved by peripheral pads. As no solder is applied, the top passivation layer of the CMOS chip is partially recessed to expose the CMOS metal layer for ease of direct bonding with the MEMS metal layer. The metal surfaces are carefully treated and bonded. The bonded samples are packaged inside 44-pin J-leaded ceramic package for testing. The functionality of the readout circuit is verified first, using off-chip MEMS, followed by verification of the bonded CMOS/MEMS chip. In both cases, the MEMS is excited by anti-phase sinusoid carriers within the frequency range 50 kHz-1 MHz. The variation in the peak-to-peak amplitude of the gain stage output is observed as the MEMS is flipped between -1 g/+1 g orientations. In addition, the phase of the output signal agrees with the flip direction. Testing for hermeticity of the Al-Au thermo-compression bond is done in accordance with the MIL-STD-883E standard. Passive sealed cavities with volume of about 1.4 × 10 -3 cm 3 are fabricated and bonded at 300°C under a bonding pressure of around 8.4 MPa for 10 mins. The cavity chips are created by deep reactive ion etching (DRIE) on silicon followed by the deposition of 50 nm of Cr adhesion layer and 150 nm of Au with electron beam evaporation method. The blanket capping chips are deposited with 100 nm of SiO 2 by plasma-enhanced chemical vapor deposition (PECVD) and 150 nm of Al by sputtering. Bubble test is used for gross leak and helium test is used for fine leak inspection. For shear strength measurement, test samples are prepared using the same processes for the samples in hermetic test, without the creation of cavities. The bonding parameters are kept the same. Results from the hermeticty and shear tests are presented and discussed.

Central nervous system (CNS) relapse of non-Hodgkin's lymphoma (NHL) is usually fatal despite therapy and effective prophylaxis is desirable. Patients at high-risk usually receive intrathecal (i.t.) prophylaxis, although its efficacy is unproven. We therefore analyzed the outcome of all patients with newly diagnosed "intermediate-grade" NHL receiving i.t. prophylaxis from 1991 to 1999. Twenty-six patients were identified and analyzed. All were free of CNS involvement at diagnosis with negative cerebrospinal fluid (CSF) cytology. Disease stage was IE in 7, and IV in 19, with a median of two extranodal sites involved. Serum lactate dehydrogenase was elevated in 65%, and the median International Prognostic Factors Index score was 3 (range 0-5). Anthracycline-based chemotherapy was used in all cases and included high-dose methotrexate +/- ara-C in six patients. The median number of i.t. treatments was 5 (range 1-12) and comprised methotrexate +/- steroid in 15, together with ara-C in 11. The actuarial 3-year CNS-relapse rate was 26 +/- 10%. Six CNS-relapses were observed and involved the spinal cord or brain parenchyma in two cases each, and the leptomeninges in four patients. Treatment-related variables associated with higher CNS-relapse rates (34-50%) were: delay of > or = 14 days from diagnosis to first i.t. injection, < 5 i.t. treatments, delay of i.t. prophylaxis until after attaining CR and systemic treatment lacking high-dose methotrexate +/- ara-C (each P < or = 0.17). I.t. CNS prophylaxis, as used here, was inadequate. Alternative approaches should be pursued.

Central nervous system (CNS) involvement by mycosis fungoides (MF) is rare and is usually seen in advanced stages with lymph node or visceral involvement. We describe a patient with advanced stage MF in large-cell transformation who presented with profound hearing loss after chemotherapy. Despite an initial differential diagnosis of vincristine-related neurotoxicity based on clinical, audiometric, and MRI investigations, CSF examination revealed lymphomatous leptomeningeal involvement. This case illustrates the importance of an awareness of the possibility of CNS involvement by MF and underlines the need for a complete neurologic evaluation including CSF examination in a patient with underlying MF who presents with a new neurological problem.

Magnetic resonance imaging (MRI) of the knee is fast assuming a major role in evaluating disorders of the knee. The major advantage of MRI is that it is a totally non-invasive procedure with superior soft tissue contrast resolution and multi-planar capabilities. In contrast to arthrography, intra-articular as well as extra-articular structures in the knee can be evaluated by MRI. Indications include studying abnormalities of the menisci, ligament, patella and quadriceps mechanisms, articular cartilage, bone, bursa and other soft tissue. A review of the literature comparing MRI to arthrography and arthroscopy of the knee, especially in relation to meniscal injuries and anterior cruciate ligament tears, shows wide ranges in the accuracy rates of MRI. There are pitfalls in the interpretation of meniscal tears on MRI like normal variants, tears at the free edge and healed or previously repaired tears. Arthrography remains a useful diagnostic modality in some of these settings.

Computerised tomographic (CT) scanning is an established modality in the diagnosis and evaluation of tumours of the nasopharynx. Magnetic resonance (MR) imaging is a newer tool which has rapidly gained acceptance in the same regard due to its innate ability to better characterise and detail soft tissue structures, and its multiplanar scanning ability. This study reviews our experience, in a series of 30 cases, with the use of MR imaging in lesions of the nasopharynx, in particular nasopharyngeal carcinoma. Most of our patients showed involvement of the pharyngeal mucosal and parapharyngeal spaces, as expected. A large number also had intracranial extension. Our sample was probably biased as patients with neurological involvement are more likely to be assessed by MR than CT. Soft tissue infiltration, particularly intracranial extension, was very clearly delineated, especially when intravenous contrast (gadolinium DTPA) was administered. Bone erosion was not well demonstrated. In current clinical practice where radiotherapy is the most common form of treatment for nasopharyngeal carcinoma however, there does not in general, appear to be any clear advantage of MR over CT in the imaging of this particular disease, although there are some exceptions.

Neurologic complications of malignancy can result from paraneoplastic manifestations, cerebral metastases or leptomeningeal involvement. Radiologic evaluation by computerised tomography (CT) has proven to be an invaluable tool in cancer patients with neurologic symptoms. Myelography and CT myelography have been the main modalities for evaluating leptomeningeal metastases. The advent of magnetic resonance imaging (MRI) with contrast has provided an alternative modality for evaluation of leptomeningeal disease. MRI as compared to CT myelography is non-invasive and at least as sensitive. The findings in two patients with leptomeningeal involvement are reported to illustrate the value of MRI.

Extracellular β-glucosidase fromAspergillus niger USDB 0355 was purified 120-fold. It gave a single band on PAGE and had an Mr of 325 000. It was optimally active at 60°C and pH 4.6. It had Km values forp-nitrophenyl-β-glucoside and cellobiose of 0.82±0.10mm and 1.33±0.20mm, respectively. It was competitively inhibited by glucose and non-competitively (mixed) inhibited by glucono-δ-lactone.

Photodarkening (PD) suppressed low numerical aperture (NA), high absorption, low loss, large mode area (LMA) fiber is an important requirement for high power fiber lasers, in both pulsed and continuous wave operation regimes. We have reported the fabrication of high absorption (∼1200 dB/m core absorption) Yb doped aluminophosphosilicate fiber with raised Ge cladding to realize low NA step index fiber [1]. The presence of Aluminium (Al) and phosphorus (P) in the core helps in lowering the PD loss by a significant margin, but some PD loss is still observed. In this work we intend to further lower the PD loss by adding Cerium (Ce) to this equimolar P:Al core. Previous reports suggests that addition of Ce to Yb:Al core significantly reduce the PD loss when the ratio of Ce oxide to Yb oxide ratio is ∼0.5–0.7 [2–4]. However, like Yb, Ce has a high molar refractivity, and all dopants (Yb, Ce and Al) push up the core NA. In our work, equimolar P:Al does not contribute to index of the core, and only the Ce and Yb raise the core NA. Furthermore, the reported raised Ge cladding technique can compensate the core NA to a desired level [1].