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Right anterolateral thoracotomy or left anterolateral thoracotomy applied to partial anomalous pulmonary venous connection correction have been reported to obtain cosmetic and less invasive outcomes as alternative approaches to median sternotomy. However, the application of different approaches is still confusing. We compared the perioperative and mid-term outcomes to seek indications of different approaches and guide surgical treatment of partial anomalous pulmonary venous connection.
Methods:
From July 2019 to August 2023, 44 patients who underwent surgical correction of partial anomalous pulmonary venous connection were recruited. Of these, 13 (29.6%) patients who underwent median sternotomy were separated into M group, 28 (63.6%) patients who underwent right anterolateral thoracotomy were separated into R group, and three (6.8%) patients who underwent left anterolateral thoracotomy were separated into L group. Clinical data were reviewed and compared between each group.
Results:
In M group, direct anastomosis accounted for the most (7, 53.8%), in R group, intra-atrial rerouting accounted for the most (22, 78.6%), and in L group, direct anastomosis accounted for the most (3, 100%). R group had shorter cardiopulmonary bypass time (70.0 ± 32.4 vs113.1 ± 83.3, p = 0.029), shorter ICU stay (1.0 ± 0.2 vs 1.9 ± 1.7, p = 0.01), shorter postoperative stay (6.0 ± 1.2 vs 8.3 ± 5.0, p = 0.021), and fewer chest tube drainage (8.4 ± 4.3 vs 13.9 ± 10.2, p = 0.026) compared with M group. Three left-sided partial anomalous pulmonary venous connection in L group adopted off-pump approach.
Conclusions:
Median sternotomy S.V.C. can be applicable to all anatomic types of partial anomalous pulmonary venous connection especially for complex types. Considering the minimally invasive advantages, we prefer applying right anterolateral thoracotomy for pulmonary vein connected to right atrium or proximal end of off-pump. Applying left anterolateral thoracotomy for left-sided partial anomalous pulmonary venous connection without atrial septal defect by off-pump.
This work investigates the spatio-temporal evolution of coherent structures in the wake of a generic high-speed train, based on a three-dimensional database from large eddy simulation. Spectral proper orthogonal decomposition (SPOD) is used to extract energy spectra and energy ranked empirical modes for both symmetric and antisymmetric components of the fluctuating flow field. The spectrum of the symmetric component shows overall higher energy and more pronounced low-rank behaviour compared with the antisymmetric one. The most dominant symmetric mode features periodic vortex shedding in the near wake, and wave-like structures with constant streamwise wavenumber in the far wake. The mode bispectrum further reveals the dominant role of self-interaction of the symmetric component, leading to first harmonic and subharmonic triads of the fundamental frequency, with remarkable deformation of the mean field. Then, the stability of the three-dimensional wake flow is analysed based on two-dimensional local linear stability analysis combined with a non-parallelism approximation approach. Temporal stability analysis is first performed for both the near-wake and the far-wake regions, showing a more unstable condition in the near-wake region. The absolute frequency of the near-wake eigenmode is determined based on spatio-temporal analysis, then tracked along the streamwise direction to find out the global mode growth rate and frequency, which indicate a marginally stable global mode oscillating at a frequency very close to the most dominant SPOD mode. The global mode wavemaker is then located, and the structural sensitivity is calculated based on the direct and adjoint modes derived from a local spatial analysis, with the maximum value localized within the recirculation region close to the train tail. Finally, the global mode shape is computed by tracking the most spatially unstable eigenmode in the far wake, and the alignment with the SPOD mode is computed as a function of streamwise location. By combining data-driven and theoretical approaches, the mechanisms of coherent structures in complex wake flows are well identified and isolated.
This study aimed to investigate the effects of esketamine (Esk) combined with dexmedetomidine (Dex) on postoperative delirium (POD) and quality of recovery (QoR) in elderly patients undergoing thoracoscopic radical lung cancer surgery.
Methods
In this prospective, randomized, and controlled study, 172 elderly patients undergoing thoracoscopic radical lung cancer surgery were divided into two groups: the Esk + Dex group (n = 86) and the Dex group a (n = 86). The primary outcome was the incidence of POD within 7 days after surgery and the overall Quality of Recovery−15 (QoR − 15) scores within 3 days after surgery. Secondary outcomes included postoperative adverse reactions, extubation time, PACU stay, and hospitalization time. Serum levels of IL-6, IL-10, S100β protein, NSE, CD3+, CD4+, and CD8+ were detected from T0 to T5.
Results
Compared with the Dex group, the incidence of POD in the Esk + Dex group was significantly lower at 7 days after surgery (14.6% vs 30.9%; P = 0.013). The QoR − 15 score was significantly increased 3 days after surgery (P < 0.01). Levels of IL-6 and CD8+ were significantly decreased, and IL − 10 levels were significantly increased at T1-T2 (P < 0.05). At T1-T4, NSE levels were significantly decreased, while CD3+ and CD4+/CD8+ values were significantly increased (P < 0.01). At T1-T5, serum S100β protein concentration decreased significantly, and CD4+ value increased significantly (P < 0.01). The incidence of nausea/vomiting and hyperalgesia decreased significantly 48 hours after surgery (P < 0.01). The duration of extubation, PACU stay, and postoperative hospitalization were significantly shortened.
Conclusions
Esketamine combined with dexmedetomidine can significantly reduce the POD incidence and improve the QoR in patients undergoing thoracoscopic radical lung cancer surgery, which may be related to the improvement of cellular immune function.
The unsteady mechanism of unstart flow for an inlet with rectangular-to-elliptical shape transition (REST) under the off-design condition at a Mach of 4 is investigated using the delay detached eddy simulation method. With the help of numerical simulations, the unsteady dynamics, especially the low-frequency characteristics of the REST inlet unstart flow, as well as the self-sustaining mechanism, is investigated. The instantaneous flow illustrates the unsteady phenomena of the REST unstart flow, including the interaction between the cowl-closure leading edge (CLE) shock and the shear layer, breathing of the separation bubble, flapping of the separation shock, instability of the shear layer and vortex shedding along the shear layer. The spectral analysis reveals that the lower frequency dynamics is associated with the breathing of the separation bubble and the flapping motion of the separation shock wave, while the higher frequency is related to the instability of the shear layer affected by cowl-closure leading edge shock and the formation of shedding vortices. Further, coherence analysis shows that the contribution of these flow structures dominating the low-frequency dynamics couple with each other. Based on the dynamic mode decomposition results, the characteristics that contribute to the unsteady behaviour of unstart flow are summarized. The streamwise vortices downstream of the separation and the shedding vortices are believed to be the main driving force of the global low-frequency unsteadiness of the REST inlet unstart flow under the off-design condition. Moreover, the CLE shock plays an important role in the process during the dominant flow structure conversion from the backflow within the separation bubble into elongated streamwise structures.
A highly compressive effect would suppress the mixing of the shear layer in a convex wall jet. The spanwise distributed protrusions at the nozzle lip are employed to achieve mixing enhancement in this study. The mixing characteristics and enhancement mechanisms are numerically investigated by the delayed detached-eddy simulation method based on the two-equation shear-stress transport model. A widely applicable flow spatiotemporal analysis method, called proper orthogonal decomposition (POD), is used to gain further insight into the dynamical behaviours of the flow instability mode. The results reveal that the centrifugal effect maintains and amplifies the initial perturbations induced by the spanwise distributed heterogeneities, resulting in forced streamwise vortices. The instabilities induced by the streamwise vortices significantly increase the growth rate of the jet half-width and the shear layer vorticity thickness. The spanwise wavelength of the streamwise vortices is consistent with the spanwise distributed forced excitation. In addition, the spanwise meandering motion of the streamwise vortices is observed, which is usually associated with the streamwise travelling wave. This is further confirmed by the POD analysis of the spanwise velocity fluctuation in both stream-radial and stream-span sections. Also, the spatial distributions of the POD modes with the highest energy provide information on the secondary instability modes. Both sinuous and varicose types of disturbances are observed in the unforced jet, whereas the forced jet seems to be dominated by the sinuous type instability, which is more easily excited than the varicose type instability. Moreover, the turbulence intensity in the forced jet is also significantly enhanced as expected due to the earlier and stronger streamwise vortices and associated instabilities. The enhanced turbulent characteristics of the highly compressible condition tend to be isotropic, whereas in the unforced jet, it is anisotropic due to the strong compressibility suppressing the spanwise turbulent fluctuations.
We explored the transmission mechanisms of corporate fraud and its punishments within social network communities. Using fraud triangle theory and trust triangle theory, we hypothesize four transmitting channels of how fraud commission and detection are affected by peers’ fraud and punishment. Based on Chinese listed corporations from 2008 to 2018, we first construct and detect interlocked social network communities with a community-detecting algorithm, and then examine hypotheses using a bivariate probit model with partial observability. Our findings indicate that peer-concealing and -hinting effects exist within social network communities. The peer-concealing effect decreases the likelihood of being detected when committing fraud, for those with more and closer fraudulent peers. The peer-hinting effect increases the likelihood of being detected when committing fraud, for those with more and closer punished peers. There is no evidence to support peer-contagion and vicarious-punishment effects. Thus, an improved understanding of the transmission mechanism of corporate fraud commission and detection within communities is provided to prevent and detect corporate fraud. In addition, stakeholders and regulators should be aware of the deviant subculture and social distancing in social network communities.
Choline plays a crucial role in hepatic lipid homeostasis by acting as a major methyl-group donor. However, despite this well-accepted fact, no study has yet explored how choline’s methyl-donor function contributes to preventing hepatic lipid dysregulation. Moreover, the potential regulatory role of Ire-1α, an ER-transmembrane transducer for the unfolded protein response (UPRer), in choline-mediated hepatic lipid homeostasis remains unexplored. Thus, this study investigated the mechanism by which choline prevents hepatic lipid dysregulation, focusing on its role as a methyl-donor and the involvement of Ire-1α in this process. To this end, a model animal for lipid metabolism, yellow catfish (Pelteobagrus fulvidraco) were fed two different diets (adequate or deficient choline diets) in vivo for 10 weeks. The key findings of studies are as follows: 1. Dietary choline, upregulated selected lipolytic and fatty acid β-oxidation transcripts promoting hepatic lipid homeostasis. 2. Dietary choline ameliorated UPRer and prevented hepatic lipid dysregulation mainly through ire-1α signalling, not perk or atf-6α signalling. 3. Choline inhibited the transcriptional expression level of ire-1α by activating site-specific DNA methylations in the promoter of ire-1α. 4. Choline-mediated ire-1α methylations reduced Ire-1α/Fas interactions, thereby further inhibiting Fas activity and reducing lipid droplet deposition. These results offer a novel insight into the direct and indirect regulation of choline on lipid metabolism genes and suggests a potential crosstalk between ire-1α signalling and choline-deficiency-induced hepatic lipid dysregulation, highlighting the critical contribution of choline as a methyl-donor in maintaining hepatic lipid homeostasis.
A continuous-wave (CW) single-longitudinal-mode (SLM) Raman laser at 1240 nm with power of up to 20.6 W was demonstrated in a free-running diamond Raman oscillator without any axial-mode selection elements. The SLM operation was achieved due to the spatial-hole-burning free nature of Raman gain and was maintained at the highest available pump power by suppressing the parasitic stimulated Brillouin scattering (SBS). A folded-cavity design was employed for reducing the perturbing effect of resonances at the pump frequency. At a pump power of 69 W, the maximum Stokes output reached 20.6 W, corresponding to a 30% optical-to-optical conversion efficiency from 1064 to 1240 nm. The result shows that parasitic SBS is the main physical process disturbing the SLM operation of Raman oscillator at higher power. In addition, for the first time, the spectral linewidth of a CW SLM diamond Raman laser was resolved using the long-delayed self-heterodyne interferometric method, which is 105 kHz at 20 W.
A single-shot measurement of electron emittance was experimentally accomplished using a focused transfer line with a dipole. The betatron phase of electrons based on laser wakefield acceleration (LWFA) is energy dependent owing to the coupling of the longitudinal acceleration field and the transverse focusing (defocusing) field in the bubble. The phase space presents slice information after phase compensation relative to the center energy. Fitting the transverse size of the electron beam at different energy slices in the energy spectrum measured 0.27 mm mrad in the experiment. The diagnosis of slice emittance facilitates local electron quality manipulation, which is important for the development of LWFA-based free electron lasers. The quasi-3D particle-in-cell simulations matched the experimental results and analysis well.
The supersonic jet over a convex wall is numerically investigated using the delayed detached-eddy simulation method based on the two-equation shear-stress transport model. The current study focuses on instabilities, turbulent statistics and the influence of compressibility effects. A widely applicable data-driven modal decomposition approach, called dynamic mode decomposition is used to gain further insight into the dynamical behaviours of the flow. The results demonstrate that streamwise vortices caused by the centrifugal force play significant roles in shear layer instabilities. The spanwise modulation of the streamwise vortices induces inflection points in the flow, resulting in secondary shear layer instability. This instability, which is sustained by the side-to-side sway of the streamwise vortices to obtain energy from the mean flow, dominates the rapid growth of the shear layer and turbulent stresses in the growth region. In the self-similar region, there is not only self-similarity of velocity profiles, but also self-similarity of normalized turbulent stresses. The compressibility effect significantly inhibits the growth of the shear layer and the formation of large-scale streamwise vortices. The investigation of turbulent stresses in the self-similar region with increasing convective Mach number indicates that the compressibility effect enhances turbulence anisotropy.
In this study, basing on the level-set and point-particle methods, we have developed a numerical methodology for simulating the dynamics of colloidal droplets under flow conditions in which the particle–particle, particle–interface and particle–fluid interactions are all taken into account efficiently. By using this methodology, we have determined the essential role of particle-laden interfaces in the deformation of colloidal droplets in simple shear flow with relatively low particle concentrations. Generally, adsorbed particles strongly enhance the deformability of the whole droplet, which is principally attributed to the particle-induced reduction of the effective surface tension. Systematic simulations are performed to reveal the detailed roles of interparticle interactions and particle surface coverage in the deformation of particle-covered droplets. Most importantly, we find the promotion effect of adsorbed particles on the droplet deformation cannot be completely included via the effective capillary number characterizing the particle-induced overall reduction of the effective surface tension, which is particularly obvious at high particle coverage. We propose two potential reasons for this surprising phenomenon, i.e. the convection-induced non-uniform distribution of adsorbed particles over the droplet surface and the particle-induced reduction of the droplet surface mobility, which have not been discussed yet in previous numerical and experimental studies of particle-covered droplets in shear flow.
Anomalous origin of the left coronary artery from the pulmonary artery is associated with high mortality if not timely surgery. We reviewed our experience with anomalous origin of the left coronary artery from the pulmonary artery to assess the preoperative variables predictive of outcome and post-operative recovery of left ventricular function.
Methods:
A retrospective review was conducted and collected data from patients who underwent anomalous origin of the left coronary artery from the pulmonary artery repair at our institute from April 2005 to December 2019. Left ventricular function was assessed by ejection fraction and the left ventricular end-diastolic dimension index. The outcomes of reimplantation repair were analysed.
Results:
A total of 30 consecutive patients underwent anomalous origin of the left coronary artery from the pulmonary artery repair, with a median age of 14.7 months (range, 1.5–59.6 months), including 14 females (46.67%). Surgery was performed with direct coronary reimplantation in 12 patients (40%) and the coronary lengthening technique in 18 (60%). Twelve patients had concomitant mitral annuloplasty. There were two in-hospital deaths (6.67%), no patients required mechanical support, and no late deaths occurred. Follow-up echocardiograms demonstrated significant improvement between the post-operative time point and the last follow-up in ejection fraction (49.43%±19.92% vs 60.21%±8.27%, p < 0.01) and in moderate or more severe mitral regurgitation (19/30 vs 5/28, p < 0.01). The left ventricular end-diastolic dimension index decreased from 101.91 ± 23.07 to 65.06 ± 12.82 (p < 0.01).
Conclusions:
Surgical repair of anomalous origin of the left coronary artery from the pulmonary artery has good mid-term results with low mortality and reintervention rates. The coronary lengthening technique has good operability and leads to excellent cardiac recovery. The decision to concomitantly correct mitral regurgitation should be flexible and be based on the pathological changes of the mitral valve and the degree of mitral regurgitation.
ABSTRACT IMPACT: Novel adipokines like tetranectin help explain why some people progress from obesity to diseases like diabetes, atherosclerosis, and dislipidemia OBJECTIVES/GOALS: Obesity has an established association with diabetes, dyslipidemia, and atherosclerosis. Preventing progression from obesity to insulin resistance requires understanding of the regulatory mechanisms involved in the loss of insulin sensitivity. Adipose tissue is well known to function as an endocrine organ that produces many kinds of adipokines. METHODS/STUDY POPULATION: Blood sample analysis from human patients and mice was used to determine associations between tetranectin and obesity. Samples were tested with a monoclonal anti-tetranectin antibody for detection with western blot. A tetranectin mutant knock out mouse line was compared to wild type littermates on high fat diet for 4 months. Insulin tolerance tests and glucose tolerance were used to determine progression to insulin resistance and glucose intolerance. Histological analysis of metabolic tissue was used to demonstrate adipocyte hypertrophy and liver steatosis. RESULTS/ANTICIPATED RESULTS: In the current study, we report the identification and initial characterization of a novel adipokine tetranectin. Tetranectin, which is coded by the C-type lectin domain family 3 member B (CLEC3B) gene, is ubiquitously expressed in various mouse tissues, whereas it is highly enriched in white adipose tissue. We found that the serum level of tetranectin was much higher in both obese and diabetic patients. Knocking out the tetranectin gene in mice protected against glucose intolerance in males but reduced insulin and glucose tolerance in females, without effects on food intake and body weight for either sex. Mechanistically, tetranectin targets liver tissues and its deficiency increases lipid accumulation in hepatocytes in females. DISCUSSION/SIGNIFICANCE OF FINDINGS: We have identified a novel adipokine which mediates a different metabolic crosstalk among tissues to maintain systemic glucose and lipid metabolism in different genders. Further investigation of tetranectin’s function could yield a new target for precise therapeutic treatment for obesity and its associated metabolic diseases in different genders
This study aimed to explore the impacts of COVID-19 outbreak on mental health status in general population in different affected areas in China.
Methods
This was a comparative study including two groups of participants: (1) general population in an online survey in Ya'an and Jingzhou cities during the COVID-19 outbreak from 10–20 February 2020; and (2) matching general population selected from the mental health survey in Ya'an in 2019 (from January to May 2019). General Health Questionnaire (GHQ-12), Self-rating Anxiety Scale (SAS), and Self-rating Depression Scale (SDS) were used.
Results
There were 1775 participants (Ya'an in 2019 and 2020: 537 respectively; Jingzhou in 2020: 701). Participants in Ya'an had a significantly higher rate of general health problems (GHQ scores ⩾3) in 2020 (14.7%) than in 2019 (5.2%) (p < 0.001). Compared with Ya'an (8.0%), participants in Jingzhou in 2020 had a significantly higher rate of anxiety (SAS scores ⩾50, 24.1%) (p < 0.001). Participants in Ya'an in 2020 had a significantly higher rate of depression (SDS scores ⩾53, 55.3%) than in Jingzhou (16.3%) (p < 0.001). The risk factors of anxiety symptoms included female, number of family members (⩾6 persons), and frequent outdoor activities. The risk factors of depression symptoms included participants in Ya'an and uptake self-protective measures.
Conclusions
The prevalence of psychological symptoms has increased sharply in general population during the COVID-19 outbreak. People in COVID-19 severely affected areas may have higher scores of GHQ and anxiety symptoms. Culture-specific and individual-based psychosocial interventions should be developed for those in need during the COVID-19 outbreak.
Continuous hBN films have been grown by means of a radio-frequency-sputtering technology, and their material properties have been investigated. The prepared hBN films can achieve good smoothness in a large area. The surface morphologies and compositions of the hBN films on Si substrate and Al film have been characterized, indicating that there is no difference. The 101-phase peak of hBN film is the strongest, and the optical band gap of the fabricated film is 5.84 eV. An attempt on the fabrication of the hBN based resistive switching (RS) device has been made by using an Ag/hBN/Al structure, leading to the observation of a clear and stable RS behavior. The device exhibits a resistance window (high-resistivity state/low-resistivity state) of around 102, and the RS behaviors of hBN film prepared by sputtering were first observed. It has been found that the opening voltage for the device is changed when a different cycle voltage is applied because of the built-in electric field increasing with the increase of applied cycle voltage. The mechanism of the RS behavior has been analyzed, which lay a foundation for the application of hBN as RS material in resistive random access memory to improve the storage density.
Limited literatures report the management of congenital left atrial appendage aneurysm (LAAA) which is extremely rare. Chest X-ray firstly showed an enlarged left cardiac silhouette for a 3-year-old patient with pneumonia. Echocardiography and magnetic resonance imaging confirmed a large cyst attached to the left atrium. Aneurysmectomy was performed through lateral thoracotomy using step-by-step method and under the guidance of transoesophageal echocardiography. We aim to show the safety and efficacy of this approach applied to children associated with congenital LAAA.
Electric-powered disposable unmanned aerial vehicles (UAVs) have wide applications due to their advantages in terms of long time flight and load capacity. Thus, improving their endurance has become an important task to enhance the performance of these UAVs. To achieve this, we investigated a battery dumping strategy which splits the battery into several packs that are used and dumped in sequence to reduce the dead weight. The Peukert effect is also considered. In this paper, the sensitivity analysis method was employed to analyse the endurance benefits for different battery weight ratios, Peukert constants and capacities, quantitatively. The results show that the endurance benefits are significantly affected by all three parameters. For ideal batteries, the endurance can be improved by 20% and 28% respectively when employing a double-pack or triple-pack battery strategy (for a battery weight ratio of 0.4), but these benefits will fall rapidly if the Peukert constant exceeds 1.0 or the battery weight declines. Besides, the endurance will be 10% longer if the lift coefficient rather than the velocity remains constant after the battery packs are dumped at a Peukert constant of 1.2.
Hydrogen is a promising alternative fuel for efficient energy production and storage, with water splitting considered one of the cleanest, environmentally friendly, and sustainable approaches to generate hydrogen. Electrochemically catalyzed water splitting plays an important role in energy conversion for the development of hydrogen-based energy sources. Porphyrin and macrocycle derivatives are versatile and can electrochemically catalyze water splitting efficiently. Because of the significance of molecule activation of electrochemical water splitting, this article covers recent progress in hydrogen evolution and oxygen evolution reactions catalyzed by porphyrin and macrocycle derivatives.
Self-assembly techniques are powerful and efficient methods for the synthesis of nanoscale materials. Using these techniques and their combination with other bottom-up fabrication processes, materials with hierarchical features can be produced with form and function in multiple length scales. We synthesize multifunctional nanoparticles through surfactant-assisted noncovalent interactions using nanoparticle building blocks. Self-assembly of these nano-building blocks results in functional materials that exhibit well-defined morphologies and hierarchical architectures for a wide range of applications. Hierarchically structured porphyrin nanocrystals can be synthesized through surfactant micelle-confined noncovalent interactions of photoactive porphyrins. We can amplify the intrinsic advantages of individual photoactive porphyrins by engineering them into well-defined active nanostructures. Through kinetic control, these nanocrystals exhibit precisely defined size, shape, and spatial arrangement of the individual porphyrins, which facilitates intermolecular mass and energy transfer. These self-assembly techniques provide remarkable flexibility to design morphologies and architectures that produce desirable properties for practical applications including photocatalysis, photodegradation, and phototherapy.
This study aimed to examine the efficacy of combining paroxetine and mirtazapine v. switching to mirtazapine, for patients with major depressive disorder (MDD) who have had an insufficient response to SSRI monotherapy (paroxetine) after the first 2 weeks of treatment.
Methods
This double-blind, randomized, placebo-controlled, three-arm study recruited participants from five hospitals in China. Eligible participants were aged 18–60 years with MDD of at least moderate severity. Participants received paroxetine during a 2-week open-label phase and patients who had not achieved early improvement were randomized to paroxetine, mirtazapine or paroxetine combined with mirtazapine for 6 weeks. The primary outcome was improvement on the Hamilton Rating Scale for Depression 17-item (HAMD-17) scores 6 weeks after randomization.
Results
A total of 204 patients who showed early non-response to paroxetine monotherapy were randomly assigned to receive either mirtazapine and placebo (n = 68), paroxetine and placebo (n = 68) or mirtazapine and paroxetine (n = 68), with 164 patients completing the outcome assessment. At week 8, the least squares (LS) mean change of HAMD-17 scores did not significantly differ among the three groups, (12.98 points) in the mirtazapine group, (12.50 points) in the paroxetine group and (13.27 points) in the mirtazapine plus paroxetine combination group. Participants in the paroxetine monotherapy group were least likely to experience adverse effects.
Conclusions
After 8 weeks follow-up, paroxetine monotherapy, mirtazapine monotherapy and paroxetine/mirtazapine combination therapy were equally effective in non-improvers at 2 weeks. The results of this trial do not support a recommendation to routinely offer additional treatment or a switch in treatment strategies for MDD patients who do not show early improvement after 2 weeks of antidepressant treatment.