TIMolol nasal spray as a treatment for epistaxis in hereditary hemorrhagic telangiectasia (HHT) – study protocol of the prospective, randomized, double-blind, controlled cross-over TIM-HHT trial

BACKGROUND: Hereditary hemorrhagic telangiectasia (HHT) is an inherited orphan disease, in which the absence of capillary beds between arterioles and venules lead to arteriovenous shunts. Epistaxis is the core symptom. Several case reports have described the nonselective beta-adrenergic receptor antagonist timolol as a successful treatment method of nosebleeds due in HHT patients. OBJECTIVE: TIM-HHT is a single-site, prospective, randomized, placebo-controlled, double-blind, cross-over study to investigate whether the efficacy of standard laser treatment of epistaxis in HHT patients can be increased by the additional use of timolol nasal spray (1 mg/d). METHODS: Twenty patients will be randomly allocated to one of two treatment sequences. Primary outcome is the severity of epistaxis determined by the Epistaxis Severity Score (ESS). Secondary outcomes are subjective satisfaction, quality of life, as well as the hemoglobin, ferritin, and transferrin levels of the participating patients. Safety outcome is assessed by means of pulse, blood pressure, and adverse events. CONCLUSION: TIM-HHT will evaluate the efficacy and safety of timolol as an additional treatment of epistaxis in HHT patients in a three-month trial period. Benzalkonium chloride is used as a placebo, which has no documented positive effect on the nasal mucosa and hence on epistaxis in HHT patients (in contrast to saline). TRIAL REGISTRATION: German Clinical Trials Register (DRKS), DRKS00020994. Registered on 10 March 2020

Evaluation of repeated micropulse cyclophotocoagulation in patients with refractory glaucoma

PURPOSE. To evaluate the efficacy and safety of repeated micropulse transscleral cyclophotocoagulation (MP-TSCPC) in patients with previously operated refractory glaucoma.MATERIALS AND METHODS. We examined 89 patients aged 74.2±7.3 years with moderate (16), advanced (58) and terminal (15) stages of uncompensated primary openangle glaucoma (POAG) before and within 12 months after the first MP-TSCPC (SUPRA 810, “Quantel Medical”, France) using standard laser parameters — 100 J. Indications for repeated MP-TSCPC were determined for 23 patients in 3 (1 patient), 6 (14 patients), 9 (8 patients) months after the first procedure. Repeated MP-TSCPC was carried out with higher impact energy — 125 J.RESULTS. After the first procedure, the hypotensive effect was achieved in 66 (74.2%) patients with refractory glaucoma lasting up to 12 months of follow-up. Repeated MP-TSCPC in 23 patients reduced the IOP by 31.2% in moderate, 31.8% in advanced, and 22.9% in terminal stages (p<0.05) by 6 months of follow-up. As a result, during 12 months of observation, MP-TSCPC (single and double) led to stabilization of the IOP in 83.1% of cases.CONCLUSION. Single and repeated micropulse TSCPC with laser energies of 100 J and 125 J is an effective and safe method of treating patients with refractory glaucoma. A single MP-TSCPC with laser energy of 100 J was effective in 66 (74.2%) patients by 12 months of observation, and single followed by repeated (laser energy of 125 J) — in 74 (83.1%) patients. It is possible to revise the basic parameters of the MP-TSCPC procedure from 100 to 125 J to achieve a longer and at the same time safe hypotensive effect in patients with refractory glaucoma.

The effect of low-intensive coherent seed irradiation on germinant growth of Scots pine and sugar beet

The success of forest and agricultural plant establishment program mainly depends on the quality of reproductive material. The study intends to offer engineers and farm owners a solution for small-size seed improvement before sowing. The effect of low-intensity coherent light on the seeds of various crops is theoretically and empirically hypothesized. The seedlots of Scots pine (Pinus sylvestris L.) and sugar beet (Beta vulgaris L.) of Russian diploid hybrid RMS-127 were germinated in a controlled environment. The germinants were produced from six seed fractions, previously irradiated with 1.274 W·m^–2 at the 632.8 nm wavelength with 1, 2, 3, 5, 10, 15 min exposure to a standard laser system, plus untreated control. Pine germinants were measured on day 15, beetroot on day 10 after germination. An increase in exposure time reduced Scots pine germination energy and capacity, while for sugar beet the results were not conclusive. On the contrary, increasing the exposure time had a positive effect on both the height and biomass growth of both Scots pine and sugar beet germinants. The 10-min exposure time resulted in maximum values for sugar beet height and biomass and Scots pine height, while the 15-min exposure time produced maximum Scots pine biomass.

Multi-frequency passive and active microrheology with optical tweezers

Optical tweezers have attracted significant attention for microrheological applications, due to the possibility of investigating viscoelastic properties in vivo which are strongly related to the health status and development of biological specimens. In order to use optical tweezers as a microrheological tool, an exact force calibration in the complex system under investigation is required. One of the most promising techniques for optical tweezers calibration in a viscoelastic medium is the so-called active–passive calibration, which allows determining both the trap stiffness and microrheological properties of the medium with the least a-priori knowledge in comparison to the other methods. In this manuscript, we develop an optimization of the active–passive calibration technique performed with a sample stage driving, whose implementation is more straightforward with respect to standard laser driving where two different laser beams are required. We performed microrheological measurements over a broad frequency range in a few seconds implementing an accurate multi-frequency driving of the sample stage. The optical tweezers-based microrheometer was first validated by measuring water, and then exemplarily applied to more viscous medium and subsequently to a viscoelastic solution of methylcellulose in water. The described method paves the way to microrheological precision metrology in biological samples with high temporal- and spatial-resolution allowing for investigation of even short time-scale phenomena.

Ground-state cooling of mechanical resonators by quantum reservoir engineering

Ground-state cooling of multiple mechanical resonators becomes vital to employ them in various applications ranging from ultra-precise sensing to quantum information processing. Here we propose a scheme for simultaneous cooling of multiple degenerate or near-degenerate mechanical resonators to their quantum ground-state, which is otherwise a challenging goal to achieve. As opposed to standard laser cooling schemes where coherence renders the motion of a resonator to its ground-state, we consider an incoherent thermal source to achieve the same aim. The underlying physical mechanism of cooling is explained by investigating a direct connection between the laser sideband cooling and “cooling by heating”. Our advantageous scheme of cooling enabled by quantum reservoir engineering can be realized in various setups, employing parametric coupling of a cooling agent with the target systems. We also discuss using non-thermal baths to simulate ultra-high temperature thermal baths for cooling.

Development and virtual validation of a novel digital workflow to rehabilitate palatal defects by using smartphone-integrated stereophotogrammetry (SPINS)

Palatal defects are rehabilitated by fabricating maxillofacial prostheses called obturators. The treatment incorporates taking deviously unpredictable impressions to facsimile the palatal defects into plaster casts for obturator fabrication in the dental laboratory. The casts are then digitally stored using expensive hardware to prevent physical damage or data loss and, when required, future obturators are digitally designed, and 3D printed. Our objective was to construct and validate an economic in-house smartphone-integrated stereophotogrammetry (SPINS) 3D scanner and to evaluate its accuracy in designing prosthetics using open source/free (OS/F) digital pipeline. Palatal defect models were scanned using SPINS and its accuracy was compared against the standard laser scanner for virtual area and volumetric parameters. SPINS derived 3D models were then used to design obturators by using (OS/F) software. The resultant obturators were virtually compared against standard medical software designs. There were no significant differences in any of the virtual parameters when evaluating the accuracy of both SPINS, as well as OS/F derived obturators. However, limitations in the design process resulted in minimal dissimilarities. With further improvements, SPINS based prosthetic rehabilitation could create a viable, low cost method for rural and developing health services to embrace maxillofacial record keeping and digitised prosthetic rehabilitation.

Introduction of Laser Pi-Grooving as Breakthrough Solution to Enhance die Strength of 40 nm ulow-k CMOS Silicon Technology during Wafer Saw Process

Nowadays, semiconductors and electronics are becoming part of our everyday activities. As the Integrated circuits become more useful to people, it also requires more function, which contain more complex and compact components. Aligned to this package requirement, the more challenging it become to package development as Silicon technology becomes more critical and complex from bare silicon to conventional MOS technology to Ultra Low-K, which requires a different strategy. The new process development in the Semiconductor industry is a necessity to cope up with these new technologies. Low-k devices always pose a big challenge in achieving good dicing quality. This is because of the weak mechanical properties of the low-k dielectric material used. Mechanical Sawing is the most popular cutting method for silicon, but with Ultra low-K technology, using mechanical sawing will lead to various sawing defects such as chippings and delamination [1,2]. These leads to the introduction of Laser Grooving to get rid of these dilemmas. Laser grooving uses heat to eradicate metals on this very thin metal wafer dicing saw streets in preparation for wafer saw process to prevent topside chippings and delamination/metal peel off [3]. These defects are not acceptable especially since the product application is a chip card. Since chip cards must be flexible and durable, they require higher die and package strength to serve its purpose. To achieve such package requirement, different method was evaluated such as standard mechanical dicing, standard Laser Grooving and the PI laser groove. The paper will discuss how we were able to achieve the quality requirement for Ultra Low-K and at the same time eliminating top reject contributor during startup of this device.

Thickness-Dependent Permeation Properties of Quenched and Standard Laser-Sintered Polyamide 12 Sheets

The laser sintering of polymers is an additive manufacturing technology that is becoming increasingly established in the industrial environment. This study investigated the thickness-dependent permeation properties of laser-sintered (LS) polymers as required to design and produce components with a special barrier performance to gaseous substances. Helium and oxygen permeation experiments were carried out on quenched and standard LS polyamide 12 (PA12) sheets generated with two, four, six, and eight layers at a constant powder layer thickness of 100 µm. The structural properties of the sheets were examined by differential scanning calorimetry, light microscopy, and X-ray micro-computed tomography. A reduction in thickness resulted in higher diffusion coefficients for both types of LS sheets. An explanation could be the large volume fraction of poorly sintered powder particles adhering to the surfaces and incomplete melting and low consolidation of the polymer at small thicknesses. The thickness-dependency of the solubility coefficients was the opposite, especially for the standard LS sheets, which might be related to the larger pore volume in thicker sheets. As both effects compensated for each other, nearly constant permeation coefficients for all thicknesses were observed. The results provide further insights into different material characteristics of thin LS PA12 structures and offer new information on factors relevant to their solution and diffusion behavior.

Ground-state cooling of mechanical resonators by hot thermal light

We propose a scheme to cool down a mechanical resonator to its quantum ground-state, which is interacting with a cavity mode via the optomechanical coupling. As opposed to standard laser cooling schemes where coherence renders the state of the resonator to its ground-state, here we use incoherent thermal light to achieve the same aim. We show that simultaneous cooling of two degenerate or near-degenerate mechanical resonators is possible in our scheme, which is otherwise a challenging goal to achieve in optomechanics. The generalization of this method to the simultaneous cooling of multiple resonators is straightforward. The underlying physical mechanism of cooling is explained by revealing a direct connection between the laser sideband cooling and “cooling by heating” in a standard optomechanical setting.