Emerging Medications and Strategies in Acute Pain Management: Evolving Role of Novel Sodium and Calcium Channel Blockers, Peptide-Based Pharmacologic Drugs, and Non-Medicinal Methods.

PURPOSE OF REVIEW: The present investigation evaluated integration of novel medication technology to enhance treatment options, while improving patient outcomes in acute pain management. In this regard, we focused on determining the role of development and utilization of cutting-edge pharmaceutical advancements, such as targeted drug delivery systems, as well as non-pharmacologic interventions in addressing acute pain states. Further research in this area is warranted related to the need for increased patient comfort and reduced adverse effects. RECENT FINDINGS: Recent innovations and techniques are discussed including pharmacologic drugs targeting sodium and calcium channels, peptide-based pharmacologic drugs, and non-medicinal methods of alleviating pain such as soothing music or virtual reality. The present investigation included review of current literature on the application of these innovative technologies, analyzing mechanisms of action, pharmacokinetics, and clinical effectiveness. Our study also investigated the potential benefits in terms of pain relief, reduced side effects, and improved patient adherence. The research critically examines the challenges and considerations associated with implementing these technologies in acute pain management, considering factors like cost, accessibility, and regulatory aspects. Additionally, case studies and clinical trials are highlighted which demonstrate practical implications of these novel medication technologies in real-world scenarios. The findings aim to provide healthcare professionals with a comprehensive understanding of the evolving landscape in acute pain management while guiding future research and clinical practices toward optimizing their use in enhancing patient care.

At-Home Saliva Sampling in Healthy Adults Using CandyCollect, a Lollipop-Inspired Device.

Respiratory infections are common in children, and there is a need for user-friendly collection methods. Here, we performed the first human subjects study using the CandyCollect device, a lollipop-inspired saliva collection device .We showed that the CandyCollect device can be used to collect salivary bacteria from healthy adults using Streptococcus mutans and Staphylococcus aureus as proof-of-concept commensal bacteria. We enrolled healthy adults in a nationwide (USA) remote study in which participants were sent study packages containing CandyCollect devices and traditional commercially available oral swabs and spit tubes. Participants sampled themselves at home, completed usability and user preference surveys, and mailed the samples back to our laboratory for analysis by qPCR. Our results showed that for participants in which a given bacterium (S. mutans or S. aureus) was detected in one or both of the commercially available methods (oral swab and/or spit tubes), CandyCollect devices had a 100% concordance with the positive result (n = 14 participants). Furthermore, the CandyCollect device was ranked the highest preference sampling method among the three sampling methods by 26 participants surveyed (combining survey results across two enrollment groups). We also showed that the CandyCollect device has a shelf life of up to 1 year at room temperature, a storage period that is convenient for clinics or patients to keep the CandyCollect device and use it any time. Taken together, we have demonstrated that the CandyCollect is a user-friendly saliva collection tool that has the potential to be incorporated into diagnostic assays in clinic visits and telemedicine.

Sputum Inflammatory Patterns are Associated with Distinct Clinical Characteristics in Subjects with Occupational Asthma Independently from the Causal Agent.

BACKGROUND AND OBJECTIVES: Clinical heterogeneity in sensitizer-induced occupational asthma (OA) and its relationship to airway inflammatory profiles remain poorly elucidated. To further characterize the interactions between induced sputum inflammatory patterns, asthma-related outcomes and the high- or low-molecular-weight category of causal agents in a large cohort of subjects with OA. METHODS: This multicenter, retrospective, cross-sectional study was conducted among 296 subjects with OA ascertained by a positive specific inhalation challenge who completed induced sputum assessment before and 24 hours after challenge exposure. RESULTS: Multivariate logistic regression analysis revealed that sputum eosinophilia ≥3% was significantly associated with a high dose of inhaled corticosteroid (odds ratio [95% confidence interval], 1.31 [1.11-1.55] for each 250-µg increment in daily dose), short-acting b2-agonist use less than once a day (3.54 [1.82-7.00]), and the level of baseline nonspecific bronchial hyperresponsiveness (mild: 2.48 [1.21-5.08]); moderate/severe: 3.40 [1.44-8.29]). Sputum neutrophilia ≥76% was associated with age (1.06 [1.01-1.11]), male gender (3.34 [1.29-9.99]), absence of corticosteroid use (5.47 [2.09-15.16]), short-acting b2-agonist use once or more a day (4.09 [1.71-10.01]), ≥2 severe exacerbations during the last 12 months at work (4.22 [1.14-14.99]), and isolated early reactions during the SIC (4.45 [1.85-11.59]). CONCLUSIONS: The findings indicate that sputum inflammatory patterns in subjects with OA are associated with distinct phenotypic characteristics and further highlight the differential effects of neutrophils and eosinophils on asthma-related outcomes. These associations between inflammatory patterns and clinical characteristics share broad similarities with what has been reported in nonoccupational asthma and are not related to the type of causal agent.

Cutaneous sensitization to aziridine preceding the onset of occupational asthma.

We describe a 47-year-old non-atopic woman, working as a spray painter in a tannery for 23 years, with a 16-year history of cutaneous symptoms and a subsequent 2-year history of asthmatic symptoms after exposure to aerosol and vapour of polyfunctional aziridine (PFA) at work. To confirm the occupational origin of the dermatitis and asthma we performed a skin prick test with PFA and a specific inhalation challenge (SIC) with PFA. Prick test with PFA elicited an immediate positive skin reaction. She developed an immediate asthmatic reaction upon SIC with PFA. The onset of occupational dermatitis before asthma is consistent with the hypothesis that the sensitization to PFA was triggered in the skin. The observation that the reactions elicited in skin and airways upon exposure to PFA exhibited the same time course, suggests a similar mechanism at both sites. Thus, the avoidance of both skin and airway exposure to PFA should be recommended in workplace hygiene practice.

Direct Measurement of Anharmonic Decay Channels of a Coherent Phonon.

We report channel-resolved measurements of the anharmonic coupling of the coherent A_{1g} phonon in photoexcited bismuth to pairs of high wave vector acoustic phonons. The decay of a coherent phonon can be understood as a parametric resonance process whereby the atomic displacement periodically modulates the frequency of a broad continuum of modes. This coupling drives temporal oscillations in the phonon mean-square displacements at the A_{1g} frequency that are observed across the Brillouin zone by femtosecond x-ray diffuse scattering. We extract anharmonic coupling constants between the A_{1g} and several representative decay channels that are within an order of magnitude of density functional perturbation theory calculations.

Mantle Sources of Recent Anatolian Intraplate Magmatism: A Regional Plume or Local Tectonic Origin?

We present an extensive study of rehomogenized olivine-hosted melt inclusions, olivine phenocrysts, and chromian spinel inclusions to explore the link between geodynamic conditions and the origin and composition of Pliocene-Quaternary intraplate magmatism in Anatolia at Kula, Ceyhan-Osmaniye, and Karacadag. Exceptional compositional variability of these products reveals early and incomplete mixing of distinct parental melts in each volcanic center, reflecting asthenospheric and lithospheric mantle sources. The studied primitive magmas consist of (1) two variably enriched ocean island basalt (OIB)-type melts in Kula; (2) both OIB-type and plume mid-ocean ridge basalt (P-MORB)-like melts beneath Toprakkale and Üçtepeler (Ceyhan-Osmaniye); and (3) two variably enriched OIB-type melts beneath Karacadag. Estimated conditions of primary melt generation are 23-9 kbar, 75-30 km, and 1415-1215 °C for Kula; 28-19 kbar, 90-65 km, and 1430-1350 °C for Toprakkale; 23-18 kbar, 75-60 km, and 1400-1355 °C for Üçtepeler; and 35-27 kbar, 115-90 km, and 1530-1455 °C for Karacadag, the deepest levels of which correspond to the depth of the lithosphere-asthenosphere boundary in all regions. Although magma ascent was likely facilitated by local deformation structures, recent Anatolian intraplate magmatism seems to be triggered by large-scale mantle flow that also affects the wider Arabian and North African regions. We infer that these volcanics form part of a much wider Arabian-North African intraplate volcanic province, which was able to invade the Anatolian upper plate through slab gaps.

Exhaled nitric oxide dynamics in asthmatic reactions induced by diisocyanates.

BACKGROUND: Isocyanate-induced asthmatic reactions are associated with delayed increase in fractional exhaled nitric oxide measured at expiratory flow of 50 mL/s (FeNO50), a biomarker of airway inflammation. The time course of FeNO increase is compatible with the activation of NO synthase, but the origin of NO production in the lung is undetermined. OBJECTIVE: The aim of this study was to define the dynamics of airway and alveolar NO during specific inhalation challenge (SIC) with isocyanates and the role of asymmetric dimethylarginine (ADMA), an endogenous inhibitor of NO synthase. METHODS: Spirometry, exhaled NO parameters (FeNO50, bronchial wall NO concentration, NO airway diffusing capacity, NO flux to luminal space, alveolar NO) and ADMA levels in exhaled breath condensate were measured before and at intervals up to 24 h after exposure to isocyanates. The results were compared between 17 SIC-positive and eight SIC-negative subjects. RESULTS: A significant FeNO50 increase in SIC-positive subjects was detected 24 h after exposure and was associated with the augmented NO flux from airway wall to the lumen, whereas airway NO diffusion and alveolar NO were not affected. The changes in NO dynamics were specific for the subjects who developed an asthmatic reaction, but were independent from the pattern and magnitude of bronchoconstriction. There was no evidence that exhaled NO is modulated by the changes in ADMA concentration. CONCLUSIONS AND CLINICAL RELEVANCE: Because isocyanate-induced increase in FeNO50 was almost exclusively determined by the increase in NO flux, the use of FeNO50 appears adequate to monitor the exhaled NO dynamics during SIC. FeNO50 measurement may provide additional information to spirometry, because bronchoconstriction and airway inflammatory responses are dissociated.

Detection of B-mode polarization at degree angular scales by BICEP2.

We report results from the BICEP2 experiment, a cosmic microwave background (CMB) polarimeter specifically designed to search for the signal of inflationary gravitational waves in the B-mode power spectrum around ℓ∼80. The telescope comprised a 26 cm aperture all-cold refracting optical system equipped with a focal plane of 512 antenna coupled transition edge sensor 150 GHz bolometers each with temperature sensitivity of ≈300 µK(CMB)√s. BICEP2 observed from the South Pole for three seasons from 2010 to 2012. A low-foreground region of sky with an effective area of 380 square deg was observed to a depth of 87 nK deg in Stokes Q and U. In this paper we describe the observations, data reduction, maps, simulations, and results. We find an excess of B-mode power over the base lensed-ΛCDM expectation in the range 30 < ℓ < 150, inconsistent with the null hypothesis at a significance of >5σ. Through jackknife tests and simulations based on detailed calibration measurements we show that systematic contamination is much smaller than the observed excess. Cross correlating against WMAP 23 GHz maps we find that Galactic synchrotron makes a negligible contribution to the observed signal. We also examine a number of available models of polarized dust emission and find that at their default parameter values they predict power ∼(5-10)× smaller than the observed excess signal (with no significant cross-correlation with our maps). However, these models are not sufficiently constrained by external public data to exclude the possibility of dust emission bright enough to explain the entire excess signal. Cross correlating BICEP2 against 100 GHz maps from the BICEP1 experiment, the excess signal is confirmed with 3σ significance and its spectral index is found to be consistent with that of the CMB, disfavoring dust at 1.7σ. The observed B-mode power spectrum is well fit by a lensed-ΛCDM+tensor theoretical model with tensor-to-scalar ratio r = 0.20_(-0.05)(+0.07), with r = 0 disfavored at 7.0σ. Accounting for the contribution of foreground, dust will shift this value downward by an amount which will be better constrained with upcoming data sets.

A mixed diet of toxic plants enables increased feeding and anti-predator defense by an insect herbivore.

Some insect herbivores sequester plant secondary metabolites (PSMs) for their own defense, raising the interesting possibility that grazing herbivores are defended by combinations of PSMs from different plant species. In this study, we tested the hypothesis that the grazing caterpillar, Grammia incorrupta, deters the ant, Aphaenogaster cockerelli, by eating a mixture of plants containing iridoid glycosides (IGs) and those containing pyrrolizidine alkaloids (PAs), and that this deterrence is greater than that attained by eating either plant alone. This hypothesis was tested against the non-mutually exclusive hypothesis that mixing plants containing PAs with those containing IGs improves growth performance. Caterpillar survival and growth were measured on three experimental diets: a PA plant, an IG plant, and a mixture of the two. We measured the degree of deterrence associated with these, and an additional experimental diet devoid of PSMs at naturally occurring A. cockerelli nests. Caterpillars fed both plants gained more mass than those fed either plant alone, but took longer to develop. These differences were not caused by diet-based variation in growth efficiency, but by eating more food when offered the mixed-plant diet relative to single-plant diets. The mixed diet was shown to provide deterrence to ants, whereas caterpillars fed single-plant diets were not significantly more deterrent than caterpillars that had eaten the PSM-free diet. We hypothesize that enhanced defense results from increased food consumption in response to multiple plant species, perhaps leading to greater PSM sequestration. Through this mechanism, bottom-up and top-down effects may mutually reinforce the grazing dietary strategy.

Initial experience with upfront arterial and perfusion imaging among ischemic stroke patients presenting within the 4.5-hour time window.

BACKGROUND: Although perfusion imaging is being evaluated as a tool to select acute ischemic stroke patients who are most likely to benefit from reperfusion therapies beyond the standard time windows, there are limited data on the utility of perfusion imaging within the intravenous (IV) thrombolytic time window. METHODS: A new stroke imaging protocol was initiated at Emory University Hospital including computed tomographic angiography (CTA) and computed tomographic perfusion (CTP). All patients presenting within 4.5 hours from last known normal time with suspected stroke were prospectively identified. Impact of CTA and CTP on the clinical management was recorded prospectively by stroke team members. RESULTS: During the study period, 87 patients met eligibility criteria for the CTA/CTP protocol, of which 83 (95%) underwent this upfront comprehensive imaging protocol and 30 (34%) received IV thrombolytics. Overall, stroke team members reported that CTA and/or CTP aided their clinical management in 39 (47%) cases, including aiding in identification of a nonstroke diagnosis (n = 18), triage to the neurologic intensive care unit (n = 9), early triage to endovascular therapy (n = 4), and initiation of IV thrombolytic for low National Institutes of Health Stroke Scale score with large vessel occlusion (n = 3). Door to needle time ≤60 minutes was achieved in only 18% of patients receiving IV thrombolysis during the study period, but had improved to 44% in the subsequent 6-month period. CONCLUSIONS: An upfront CTA/CTP protocol aided stroke team decision-making in nearly half of cases. Implementation of a CTA/CTP protocol was associated with a learning curve of 6 months before door to needle time ≤60 minutes returned to similar rates as the pre-CTA/CTP protocol.

Anatomical Variant of the Lateral Circumflex Femoral Artery: A Cadaveric Case Report.

The lateral circumflex femoral artery (LCFA), a branch of the deep femoral artery (DFA), supplies the muscular and fascial anatomy of the anterior thigh. An undocumented variation of the LCFA was discovered during a dissection of the lower extremities. The LCFA is a vital vessel that can be used in coronary artery bypass grafts (CABGs) and reconstructive and bypass surgical procedures. On the other hand, the LCFA is susceptible to iatrogenic damage during surgeries involving the hip joint and procedures such as femoral nerve blocks. Knowledge of variations in the origin and course of the LFCA, like many other anatomical structures, is an important concept that physicians and health care providers must be aware of when performing anterior thigh procedures. This case report shows an interesting duplication of the LCFA, the first originating superiorly from the common femoral artery (CFA) and the second from the deep femoral artery (DFA) inferiorly. Both LCFAs exhibited typical trifurcation into ascending, descending, and transverse branches.

X-linked dyskeratosis congenita is caused by mutations in a highly conserved gene with putative nucleolar functions.

X-linked recessive dyskeratosis congenita (DKC) is a rare bone-marrow failure disorder linked to Xq28. Hybridization screening with 28 candidate cDNAs resulted in the detection of a 3' deletion in one DKC patient with a cDNA probe (derived from XAP101). Five different missense mutations in five unrelated patients were subsequently identified in XAP101, indicating that it is the gene responsible for X-linked DKC (DKC1). DKC1 is highly conserved across species barriers and is the orthologue of rat NAP57 and Saccharomyces cerevisiae CBF5. The peptide dyskerin contains two TruB pseudouridine (psi) synthase motifs, multiple phosphorylation sites, and a carboxy-terminal lysine-rich repeat domain. By analogy to the function of the known dyskerin orthologues, involvement in the cell cycle and nucleolar function is predicted for the protein.

Successful rehabilitation and release of a powerful owl chick with suspected rodenticide poisoning.

The successful rehabilitation and release of raptor chicks can be challenging, especially when the chicks are still in the post-fledging dependency period. Here, we report on a recently fledged powerful owl chick that was held in care for 33 days before being successfully reunited with its parents. We document the steps undertaken during the entire process from collection from the wild to post-release monitoring and recommend clinical procedures for treatment of raptors entering veterinary facilities. Success of this rehabilitation was facilitated by early care and treatment for potential rodenticide poisoning, as well as the integration of citizen scientists monitoring the family unit in the field while the chick was in care and during the post-release period. Given the emerging evidence of widespread rodenticide poisoning in raptors both in Australia and globally, it is critical to suspect all raptors may have been exposed to anticoagulant rodenticides and commence treatment with vitamin K immediately. Routine treatment for rodenticides early increases the probability of successful recovery post-trauma as well as reducing the time in treatment as much as possible.

Mortality and histopathology in sheepshead minnow (Cyprinodon variegatus) larvae exposed to pectenotoxin-2 and Dinophysis acuminata.

Toxic species of the dinoflagellate genus Dinophysis can produce diarrheic toxins including okadaic acid (OA) and dinophysistoxins (DTXs), and the non-diarrheic pectenotoxins (PTXs). Okadaic acid and DTXs cause diarrheic shellfish poisoning (DSP) in human consumers, and also cause cytotoxic, immunotoxic and genotoxic effects in a variety of mollusks and fishes at different life stages in vitro. The possible effects of co-produced PTXs or live cells of Dinophysis to aquatic organisms, however, are less understood. Effects on an early life stage of sheepshead minnow (Cyprinodon variegatus), a common finfish in eastern USA estuaries, were evaluated using a 96-h toxicity bioassay. Three-week old larvae were exposed to PTX2 concentrations from 50 to 4000 nM, live Dinophysis acuminata culture (strain DAVA01), live cells resuspended in clean medium or culture filtrate. This D. acuminata strain produced mainly intracellular PTX2 (≈ 21 pg cell-1), with much lower levels of OA and dinophysistoxin-1. No mortality or gill damages were observed in larvae exposed to D. acuminata (from 5 to 5500 cells mL-1), resuspended cells and culture filtrate. However, exposure to purified PTX2 at intermediate to high concentrations (from 250 to 4000 nM) resulted in 8 to 100% mortality after 96 h (24-h LC50 of 1231 nM). Histopathology and transmission electron microscopy of fish exposed to intermediate to high PTX2 concentrations revealed important gill damage, including intercellular edema, necrosis and sloughing of gill respiratory epithelia, and damage to the osmoregulatory epithelium, including hypertrophy, proliferation, redistribution and necrosis of chloride cells. Tissue damage in gills is likely caused by the interaction of PTX2 with the actin cytoskeleton of the affected gill epithelia. Overall, the severe gill pathology observed following the PTX2 exposure suggested death was due to loss of respiratory and osmoregulatory functions in C. variegatus larvae.

At-home saliva sampling in healthy adults using CandyCollect, a lollipop-inspired device.

Respiratory infections are common in children, and there is a need for user-friendly collection methods. Here, we performed the first human subjects study using the CandyCollect device, a lollipop inspired saliva collection device. 1 We showed the CandyCollect device can be used to collect salivary bacteria from healthy adults using Streptococcus mutans and Staphylococcus aureus as proof-of-concept commensal bacteria. We enrolled healthy adults in a nationwide (USA) remote study in which participants were sent study packages containing CandyCollect devices and traditional commercially available oral swabs and spit tubes. Participants sampled themselves at home, completed usability and user preference surveys, and mailed the samples back to our laboratory for analysis by qPCR. Our results showed that for participants in which a given bacterium ( S. mutans or S. aureus ) was detected in one or both of the commercially available methods (oral swab and/or spit tubes), CandyCollect devices had a 100% concordance with the positive result (n=14 participants). Furthermore, the CandyCollect device was ranked the highest preference sampling method among the three sampling methods by 26 participants surveyed (combining survey results across two enrollment groups). We also showed that the CandyCollect device has a shelf life of up to 1 year at room temperature, a storage period that is convenient for clinics or patients to keep the CandyCollect device and use it any time. Taken together, we have demonstrated that the CandyCollect is a user-friendly saliva collection tool that has the potential to be incorporated into diagnostic assays in clinic visits and telemedicine.

High-energy, ceramic-disk Yb:LuAG laser amplifier.

We report the first short-pulse amplification results to several hundred millijoule energies in ceramic Yb:LuAG. We have demonstrated ns-pulse output from a diode-pumped Yb:LuAG amplifier at a maximum energy of 580 mJ and a peak optical-to-optical efficiency of 28% at 550 mJ. In cavity dumped operation of a nanosecond oscillator we obtained 1 mJ at up to 100 Hz repetition rate. A gain bandwidth of 5.4 nm was achieved at room temperature by measuring the small-signal single-pass gain. Furthermore, we compared our results with Yb:YAG within the same amplifier system.

Abdominal radical trachelectomy in West London.

OBJECTIVE: Traditionally, the surgical management of invasive cervical carcinoma that has progressed beyond microinvasion has been a radical abdominal hysterectomy. However, this results in the loss of fertility, with significant consequences for the young patient. This report describes abdominal radical trachelectomy (ART) as a potential replacement for radical hysterectomy in patients with stage IA2-IIA cervical cancer who desire a fertility-sparing procedure without decreasing the curative rates. DESIGN: Observational, retrospective study. SETTING: Teaching hospital and regional cancer centre in London, UK. POPULATION: Patients undergoing ART. METHODS: Patients presenting during the period 2000-2009 with cervical cancer stage IA2-IIA were offered a trachelectomy, if they expressed a desire to preserve fertility. The type of trachelectomy (vaginal/abdominal) was chosen based on patient anatomy and neoplastic and magnetic resonance imaging characteristics. Each patient was counselled as to the experimental nature of the procedure. MAIN OUTCOME MEASURES: Survival, recurrence and fertility issues among ART patients. RESULTS: A total of 30 patients underwent ART (open and laparoscopic) between 2001 and 2009. Three patients presented with a recurrence, two of which have died (median follow-up: 24 months). Only three patients required further surgical re-intervention because of operative complications. Ten patients attempted to conceive, resulting in three conceptions (30%) and two live children. CONCLUSIONS: Abdominal radical trachelectomy provides a feasible, cost-effective and safe treatment option for young women who have been diagnosed with early-stage cervical cancer and wish to preserve their fertility.

Antigen-specific T cell responses to BK polyomavirus antigens identify functional anti-viral immunity and may help to guide immunosuppression following renal transplantation.

Infection with the polyoma virus BK (BKV) is a major cause of morbidity following renal transplantation. Limited understanding of the anti-viral immune response has prevented the design of a strategy that balances treatment with the preservation of graft function. The proven utility of interferon-gamma enzyme-linked immunospot (ELISPOT) assays to measure T cell responses in immunocompetent hosts was the basis for trying to develop a rational approach to the management of BKV following renal transplantation. In a sample of transplant recipients and healthy controls, comparisons were made between T cell responses to the complete panel of BKV antigens, the Epstein-Barr virus (EBV) antigens, BZLF1 and EBNA1, and the mitogen phytohaemagglutinin (PHA). Correlations between responses to individual antigens and immunosuppressive regimens were also analysed. Antigen-specific T cell responses were a specific indicator of recent or ongoing recovery from BKV infection (P < 0·05), with responses to different BKV antigens being highly heterogeneous. Significant BKV immunity was undetectable in transplant patients with persistent viral replication or no history of BKV reactivation. Responses to EBV antigens and mitogen were reduced in patients with BKV reactivation, but these differences were not statistically significant. The T cell response to BKV antigens is a useful and specific guide to recovery from BKV reactivation in renal transplant recipients, provided that the full range of antigenic responses is measured.

Optimising the efficiency of pulsed diode pumped Yb:YAG laser amplifiers for ns pulse generation.

We present a numerical model of a pulsed, diode-pumped Yb:YAG laser amplifier for the generation of high energy ns-pulses. This model is used to explore how optical-to-optical efficiency depends on factors such as pump duration, pump spectrum, pump intensity, doping concentration, and operating temperature. We put special emphasis on finding ways to achieve high efficiency within the practical limitations imposed by real-world laser systems, such as limited pump brightness and limited damage fluence. We show that a particularly advantageous way of improving efficiency within those constraints is operation at cryogenic temperature. Based on the numerical findings we present a concept for a scalable amplifier based on an end-pumped, cryogenic, gas-cooled multi-slab architecture.