Introducing Porosity into Refractory Molybdenum Boride through Controlled Decomposition of a Metastable Mo-Al-B Precursor.

The high temperatures typically required to synthesize refractory compounds preclude the formation of high-energy morphological features, including nanoscopic pores that are beneficial for applications, such as catalysis, that require higher surface areas. Here, we demonstrate a low-temperature multistep pathway to engineer mesoporosity into a catalytic refractory material. Mesoporous molybdenum boride, α-MoB, forms through the controlled thermal decomposition of nanolaminate-containing sheets of the metastable MAB (metal-aluminum-boron) phase Mo2AlB2 and amorphous alumina. Upon heating, the Mo2AlB2 layers of the Mo2AlB2-AlOx nanolaminate, which is derived from MoAlB, begin to bridge and decompose, forming inclusions of alumina in a framework of α-MoB. The alumina can be dissolved in aqueous sodium hydroxide in an autoclave, forming α-MoB with empty and accessible pores. Statistical analysis of the morphologies and dimensions of the pores reveals a correlation with grain size, which relates to the pathway by which the alumina inclusions form. The transformation of Mo2AlB2 to α-MoB is topotactic due to crystal structure relationships, resulting in a high density of stacking faults that can be modeled to account for the observed experimental diffraction data. Porosity was validated by comparing surface areas and demonstrating catalytic viability for the hydrogen evolution reaction.

Incorporation of Metal Phosphide Domains into Colloidal Hybrid Nanoparticles.

Colloidal hybrid nanoparticles have generated considerable attention in the inorganic nanomaterials community. The combination of different materials within a single nanoparticle can lead to synergistic properties that can enable new properties, new applications, and the discovery of new phenomena. As such, methodologies for the synthesis of hybrid nanoparticles that integrate metal-metal, metal chalcogenide, metal oxide, and oxide-chalcogenide domains have been extensively reported in the literature. However, colloidal hybrid nanoparticles containing metal phosphide domains are rare, despite being attractive systems for their potentially unique catalytic, photocatalytic, and optoelectronic properties. In this Forum Article, we report a study of the synthesis of colloidal hybrid nanoparticles that couple the metal phosphides Ni2P and CoxPy with Au, Ag, PbS, and CdS using heterogeneous seeded-growth reactions. We also investigate the transformation of Au-Ni heterodimers to Au-Ni2P, where phosphidation of preformed metal-metal hybrid nanoparticles offers an alternative route to metal phosphide systems. We also study sequential cation-exchange reactions to target specific metal phosphide hybrids, i.e., the transformation of Ni2P-PbS into Ni2P-Ag2S and then Ni2P-CdS. Throughout all of these pathways, the accompanying discussion emphasizes the synthetic rationale, as well as the challenges in synthesis and characterization that are unique to these systems. In particular, the observation of oxide shells that surround the phosphide domains has implications for the potential photocatalytic applications of these hybrid nanoparticles.

Phosphine-Induced Phase Transition in Copper Sulfide Nanoparticles Prior to Initiation of a Cation Exchange Reaction.

Cation exchange reactions of colloidal copper sulfide nanoparticles are widely used to produce derivative nanoparticles having unique compositions, metastable crystal structures, and complex heterostructures. The copper sulfide crystal structure plays a key role in the mechanism by which cation exchange occurs and the product that forms. Here, we show that digenite copper sulfide nanoparticles undergo a spontaneous phase transition to tetragonal chalcocite in situ, prior to the onset of cation exchange. Room-temperature sonication of digenite (Cu1.8S) in trioctylphosphine, a Lewis base that drives cation exchange, extracts sulfur to produce tetragonal chalcocite (Cu2S). The subtle structural differences between digenite and tetragonal chalcocite are believed to influence the accessibility of cation diffusion channels and concomitantly the mechanism of cation exchange. Structural relationships in nanocrystal cation exchange are therefore dynamic, and intermediates generated in situ must be considered.

Antibiotic treatment for Burkholderia cepacia complex in people with cystic fibrosis experiencing a pulmonary exacerbation.

BACKGROUND: Chronic pulmonary infection is a hallmark of lung disease in cystic fibrosis. Infections dominated by organisms of the Burkholderia cepacia complex, a group of at least 18 closely-related species of gram-negative bacteria, are particularly difficult to treat. These infections may be associated with a fulminant necrotising pneumonia. Burkholderia cepacia complex bacteria are resistant to many common antibiotics and able to acquire resistance against many more. Following patient segregation in cystic fibrosis medical care, the more virulent epidemic strains are not as frequent, and new infections are more likely to be with less virulent environmentally-acquired strains. Although evidence-based guidelines exist for treating respiratory exacerbations involving Pseudomonas aeruginosa, these cannot be extended to Burkholderia cepacia complex infections. This review, which is an update of a previous review, aims to assess the available trial evidence for the choice and application of treatments for these infections. OBJECTIVES: To assess the effectiveness and safety of different antibiotic regimens in people with cystic fibrosis experiencing an exacerbation and chronically infected with organisms of the Burkholderia cepacia complex. SEARCH METHODS: We searched the Cochrane Cystic Fibrosis Trials Register, compiled from electronic database searches and handsearching of journals and conference abstract books. We also searched the reference lists of relevant articles and reviews. Date of latest search: 29 May 2019. SELECTION CRITERIA: Randomised and quasi-randomised controlled trials of treatments for exacerbations of pulmonary symptoms in people with cystic fibrosis chronically infected with organisms of the Burkholderia cepacia complex. DATA COLLECTION AND ANALYSIS: No relevant trials were identified. MAIN RESULTS: No trials were included in this review. AUTHORS' CONCLUSIONS: Burkholderia cepacia complex infections present a significant challenge for people with cystic fibrosis and their clinicians. The incidence is likely to increase as the cystic fibrosis population ages; and managing and treating these infections will become more important. There is a lack of trial evidence to guide decision making and no conclusions can be drawn from this review about the optimal antibiotic regimens for people with cystic fibrosis who have chronic Burkholderia cepacia complex infections. Clinicians must continue to assess each person individually, taking into account in vitro antibiotic susceptibility data, previous clinical responses and their own experience. Multicentre randomised clinical trials are needed to assess the effectiveness of different antibiotic regimens in people with cystic fibrosis infected with organisms of the Burkholderia cepacia complex.

Multi-Step Topochemical Pathway to Metastable Mo2AlB2 and Related Two-Dimensional Nanosheet Heterostructures.

The rational synthesis of metastable inorganic solids, which is a grand challenge in solid-state chemistry, requires the development of kinetically controlled reaction pathways. Topotactic strategies can achieve this goal by chemically modifying reactive components of a parent structure under mild conditions to produce a closely related analogue that has otherwise inaccessible structures and/or compositions. Refractory materials, such as transition metal borides, are difficult to structurally manipulate at low temperatures because they generally are chemically inert and held together by strong covalent bonds. Here, we report a multistep low-temperature topotactic pathway to bulk-scale Mo2AlB2, which is a metastable phase that has been predicted to be the precursor needed to access a synthetically elusive family of 2-D metal boride (MBene) nanosheets. Room-temperature chemical deintercalation of Al from the stable compound MoAlB (synthesized as a bulk powder at 1400 °C) formed highly strained and destabilized MoAl1-xB, which was size-selectively precipitated to isolate the most reactive submicron grains and then annealed at 600 °C to deintercalate additional Al and crystallize Mo2AlB2. Further heating resulted in topotactic decomposition into bulk-scale Mo2AlB2-AlOx nanolaminates that contain Mo2AlB2 nanosheets with thickness of 1-3 nm interleaved by 1-3 nm of amorphous aluminum oxide. The combination of chemical destabilization, size-selective precipitation, and low-temperature annealing provides a potentially generalizable kinetic pathway to metastable variants of refractory compounds, including bulk Mo2AlB2 and Mo2AlB2-AlOx nanosheet heterostructures, and opens the door to other previously elusive 2-D materials such as 2-D MoB (MBene).

Return to work and lost earnings after acute respiratory distress syndrome: a 5-year prospective, longitudinal study of long-term survivors.

BACKGROUND: Delayed return to work is common after acute respiratory distress syndrome (ARDS), but has undergone little detailed evaluation. We examined factors associated with the timing of return to work after ARDS, along with lost earnings and shifts in healthcare coverage. METHODS: Five-year, multisite prospective, longitudinal cohort study of 138 2-year ARDS survivors hospitalised between 2004 and 2007. Employment and healthcare coverage were collected via structured interview. Predictors of time to return to work were evaluated using Fine and Grey regression analysis. Lost earnings were estimated using Bureau of Labor Statistics data. RESULTS: Sixty-seven (49%) of the 138 2-year survivors were employed prior to ARDS. Among 64 5-year survivors, 20 (31%) never returned to work across 5-year follow-up. Predictors of delayed return to work (HR (95% CI)) included baseline Charlson Comorbidity Index (0.77 (0.59 to 0.99) per point; p=0.04), mechanical ventilation duration (0.67 (0.55 to 0.82) per day up to 5 days; p<0.001) and discharge to a healthcare facility (0.49 (0.26 to 0.93); p=0.03). Forty-nine of 64 (77%) 5-year survivors incurred lost earnings, with average (SD) losses ranging from US$38 354 (21,533) to US$43 510 (25,753) per person per year. Jobless, non-retired survivors experienced a 33% decrease in private health insurance and concomitant 37% rise in government-funded coverage. CONCLUSIONS: Across 5-year follow-up, nearly one-third of previously employed ARDS survivors never returned to work. Delayed return to work was associated with patient-related and intensive care unit/hospital-related factors, substantial lost earnings and a marked rise in government-funded healthcare coverage. These important consequences emphasise the need to design and evaluate vocation-based interventions to assist ARDS survivors return to work.

Healthcare Resource Use and Costs in Long-Term Survivors of Acute Respiratory Distress Syndrome: A 5-Year Longitudinal Cohort Study.

OBJECTIVE: To evaluate the time-varying relationship of annual physical, psychiatric, and quality of life status with subsequent inpatient healthcare resource use and estimated costs. DESIGN: Five-year longitudinal cohort study. SETTING: Thirteen ICUs at four teaching hospitals. PATIENTS: One hundred thirty-eight patients surviving greater than or equal to 2 years after acute respiratory distress syndrome. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Postdischarge inpatient resource use data (e.g., hospitalizations, skilled nursing, and rehabilitation facility stays) were collected via a retrospective structured interview at 2 years, with prospective collection every 4 months thereafter, until 5 years postacute respiratory distress syndrome. Adjusted odds ratios for hospitalization and relative medians for estimated episode of care costs were calculated using marginal longitudinal two-part regression. The median (interquartile range) number of inpatient admission hospitalizations was 4 (2-8), with 114 patients (83%) reporting greater than or equal to one hospital readmission. The median (interquartile range) estimated total inpatient postdischarge costs over 5 years were $58,500 ($19,700-157,800; 90th percentile, $328,083). Better annual physical and quality of life status, but not psychiatric status, were associated with fewer subsequent hospitalizations and lower follow-up costs. For example, greater grip strength (per 6 kg) had an odds ratio (95% CI) of 0.85 (0.73-1.00) for inpatient admission, with 23% lower relative median costs, 0.77 (0.69-0.87). CONCLUSIONS: In a multisite cohort of long-term acute respiratory distress syndrome survivors, better annual physical and quality of life status, but not psychiatric status, were associated with fewer hospitalizations and lower healthcare costs.

Pneumothorax in cystic fibrosis: beyond the guidelines.

Pneumothorax is a serious but common complication in patients with cystic fibrosis (CF). It has adverse prognostic implications as well as associations with subsequent reduction in lung function and significant risk of recurrence. Management dilemmas frequently occur that are beyond current guidelines. We review the evidence and highlight management difficulties in pneumothoraces in CF.

Antibiotic treatment for Burkholderia cepacia complex in people with cystic fibrosis experiencing a pulmonary exacerbation.

BACKGROUND: Chronic pulmonary infection is a hallmark of lung disease in cystic fibrosis. Infections dominated by organisms of the Burkholderia cepacia complex, a group of at least 18 closely-related species of gram-negative bacteria, are particularly difficult to treat. These infections may be associated with a fulminant necrotising pneumonia. Burkholderia cepacia complex bacteria are resistant to many common antibiotics and able to acquire resistance against many more. Following patient segregation in cystic fibrosis medical care, the more virulent epidemic strains are not as frequent, and new infections are more likely to be with less virulent environmentally-acquired strains. Although evidence-based guidelines exist for treating respiratory exacerbations involving Pseudomonas aeruginosa, these cannot be extended to Burkholderia cepacia complex infections. This review, which is an update of a previous review, aims to assess the available trial evidence for the choice and application of treatments for these infections. OBJECTIVES: To assess the effectiveness and safety of different antibiotic regimens in people with cystic fibrosis experiencing an exacerbation and chronically infected with organisms of the Burkholderia cepacia complex. SEARCH METHODS: We searched the Cochrane Cystic Fibrosis Trials Register, compiled from electronic database searches and handsearching of journals and conference abstract books. We also searched the reference lists of relevant articles and reviews.Date of latest search: 28 August 2015. SELECTION CRITERIA: Randomised and quasi-randomised controlled trials of treatments for exacerbations of pulmonary symptoms in people with cystic fibrosis chronically infected with organisms of the Burkholderia cepacia complex. DATA COLLECTION AND ANALYSIS: No relevant trials were identified. MAIN RESULTS: No trials were included in this review. AUTHORS' CONCLUSIONS: Burkholderia cepacia complex infections present a significant challenge for people with cystic fibrosis and their clinicians. The incidence is likely to increase as the cystic fibrosis population ages; and managing and treating these infections will become more important. There is a lack of trial evidence to guide decision making and no conclusions can be drawn from this review about the optimal antibiotic regimens for people with cystic fibrosis who have chronic Burkholderia cepacia complex infections. Clinicians must continue to assess each person individually, taking into account in vitro antibiotic susceptibility data, previous clinical responses and their own experience. Multicentre randomised clinical trials are needed to assess the effectiveness of different antibiotic regimens in people with cystic fibrosis infected with organisms of the Burkholderia cepacia complex.

Increasing the dose of acute rehabilitation: is there a benefit?

Rehabilitation interventions, including physiotherapy and occupational therapy, can improve patient outcomes; however, the optimal duration and frequency of inpatient rehabilitation interventions is uncertain. In a recent randomized controlled trial published in BMC Medicine, 996 patients in two publicly-funded Australian metropolitan rehabilitation facilities were assigned to physiotherapy and occupational therapy delivered Monday through Friday (five days/week control group) versus Monday through Saturday (six days/week intervention group). This increased dose of rehabilitation in the intervention group resulted in greater functional independence and quality of life at discharge, with a trend towards significant improvement at six-month follow-up. Moreover, the length of stay for the intervention group was shorter by two days (95% CI 0 to 4, P = 0.10). Hence, in the acute inpatient rehabilitation setting, a larger dose of physiotherapy and occupational therapy, via six versus five days/week treatment, improves patient outcomes and potentially reduces overall length of stay and costs. Please see related research: http://www.biomedcentral.com/1741-7015/11/198.

ICU early physical rehabilitation programs: financial modeling of cost savings.

OBJECTIVE: To evaluate the potential annual net cost savings of implementing an ICU early rehabilitation program. DESIGN: Using data from existing publications and actual experience with an early rehabilitation program in the Johns Hopkins Hospital Medical ICU, we developed a model of net financial savings/costs and presented results for ICUs with 200, 600, 900, and 2,000 annual admissions, accounting for both conservative- and best-case scenarios. Our example scenario provided a projected financial analysis of the Johns Hopkins Medical ICU early rehabilitation program, with 900 admissions per year, using actual reductions in length of stay achieved by this program. SETTING: U.S.-based adult ICUs. INTERVENTIONS: Financial modeling of the introduction of an ICU early rehabilitation program. MEASUREMENTS AND MAIN RESULTS: Net cost savings generated in our example scenario, with 900 annual admissions and actual length of stay reductions of 22% and 19% for the ICU and floor, respectively, were $817,836. Sensitivity analyses, which used conservative- and best-case scenarios for length of stay reductions and varied the per-day ICU and floor costs, across ICUs with 200-2,000 annual admissions, yielded financial projections ranging from -$87,611 (net cost) to $3,763,149 (net savings). Of the 24 scenarios included in these sensitivity analyses, 20 (83%) demonstrated net savings, with a relatively small net cost occurring in the remaining four scenarios, mostly when simultaneously combining the most conservative assumptions. CONCLUSIONS: A financial model, based on actual experience and published data, projects that investment in an ICU early rehabilitation program can generate net financial savings for U.S. hospitals. Even under the most conservative assumptions, the projected net cost of implementing such a program is modest relative to the substantial improvements in patient outcomes demonstrated by ICU early rehabilitation programs.

Chronic cough and inflammatory bowel disease: an under-recognised association?

Respiratory complications of inflammatory bowel disease (IBD) are common and may be under-recognised. Chronic cough may present many years after a colectomy for IBD, is typically productive and can be very responsive to inhaled corticosteroids. https://bit.ly/3DrHNoy.

Computationally Guided Synthesis of MXenes by Dry Selective Extraction.

MXenes are a rapidly growing family of 2D transition metal carbides and nitrides that are promising for various applications, including energy storage and conversion, electronics, and healthcare. Hydrofluoric-acid-based etchants are typically used for large-scale and high-throughput synthesis of MXenes, which also leads to a mixture of surface terminations that impede MXene properties. Herein, a computational thermodynamic model with experimental validation is presented to explore the feasibility of fluorine-free synthesis of MXenes with uniform surface terminations by dry selective extraction (DSE) from precursor MAX phases using iodine vapors. A range of MXenes and respective precursor compositions are systematically screened using first-principles calculations to find candidates with high phase stability and low etching energy. A thermodynamic model based on the "CALculation of PHAse Diagrams" (CALPHAD) approach is further demonstrated, using Ti3 C2 I2 as an example, to assess the Gibbs free energy of the DSE reaction and the state of the byproducts as a function of temperature and pressure. Based on the assessment, the optimal synthesis temperature and vapor pressure are predicted and further verified by experiments. This work opens an avenue for scalable, fluorine-free dry synthesis of MXenes with compositions and surface chemistries that are not accessible using wet chemical etching.

Vanadium and Niobium MXenes-Bilayered V2 O5 Asymmetric Supercapacitors.

MXenes offer high metallic conductivity and redox capacitance that are attractive for high-power, high-energy storage devices. However, they operate limitedly under high anodic potentials due to irreversible oxidation. Pairing them with oxides to design asymmetric supercapacitors may expand the voltage window and increase the energy storage capabilities. Hydrated lithium preintercalated bilayered V2 O5 ( δ-Lix V2 O5 ·nH2 O) is attractive for aqueous energy storage due to its high Li capacity at high potentials; however, its poor cyclability remains a challenge. To overcome its limitations and achieve a wide voltage window and excellent cyclability, it is combined with V2 C and Nb4 C3 MXenes. Asymmetric supercapacitors employing lithium intercalated V2 C (Li-V2 C) or tetramethylammonium intercalated Nb4 C3 (TMA-Nb4 C3 ) MXenes as the negative electrode, and a δ-Lix V2 O5 ·nH2 O composite with carbon nanotubes as the positive electrode in 5 m LiCl electrolyte operate over wide voltage windows of 2 and 1.6 V, respectively. The latter shows remarkably high cyclability-capacitance retention of ≈95% after 10 000 cycles. This work highlights the importance of selecting appropriate MXenes to achieve a wide voltage window and a long cycle life in combination with oxide anodes to demonstrate the potential of MXenes beyond Ti3 C2 in energy storage.

M5X4: A Family of MXenes.

MXenes are two-dimensional (2D) transition metal carbides, nitrides, and carbonitrides typically synthesized from layered MAX-phase precursors. With over 50 experimentally reported MXenes and a near-infinite number of possible chemistries, MXenes make up the fastest-growing family of 2D materials. They offer a wide range of properties, which can be altered by their chemistry (M, X) and the number of metal layers in the structure, ranging from two in M2XTx to five in M5X4Tx. Only one M5X4 MXene, Mo4VC4, has been reported. Herein, we report the synthesis and characterization of two M5AX4 mixed transition metal MAX phases, Ti2.5Ta2.5AlC4 and Ti2.675Nb2.325AlC4, and their successful topochemical transformation into Ti2.5Ta2.5C4Tx and Ti2.675Nb2.325C4Tx MXenes. The resulting MXenes were delaminated into single-layer flakes, analyzed structurally, and characterized for their thermal and optical properties. This establishes a family of M5AX4 MAX phases and their corresponding MXenes. These materials were experimentally produced based on guidance from theoretical predictions, leading to more exciting applications for MXenes.

Influence of highly effective modulator therapy on the sputum proteome in cystic fibrosis.

BACKGROUND: There have been dramatic clinical improvements in people with cystic fibrosis (PwCF) commenced on the cystic fibrosis conductance regulator (CFTR) modulator elexacaftor/tezacaftor/ivacaftor (ETI). Sputum proteomics is a powerful research technique capable of identifying important airway disease mechanisms. Using this technique, we evaluated how ETI changes the sputum proteome in PwCF. METHODS: Sputum samples from 21 CF subjects pre- and post- ETI, 6 CF controls ineligible for ETI, and 15 healthy controls were analysed by liquid chromatography mass spectrometry. RESULTS: Post-ETI, mean FEV1 % increased by 13.7 % (SD 7.9). Principal component and hierarchical clustering analysis revealed that the post-ETI proteome shifted to an intermediate state that was distinct from pre-ETI and healthy controls, even for those achieving normal lung function. Functional analysis showed incomplete resolution of neutrophilic inflammation. The CF control sputum proteome did not alter. At the protein-level many more proteins increased in abundance than decreased following ETI therapy (80 vs 30; adjusted p value <0.05), including many that have anti-inflammatory properties. Of those proteins that reduced in abundance many were pro-inflammatory neutrophil-derived proteins. Several important respiratory proteases were unchanged. CONCLUSIONS: Sputum proteomics can provide insights into CF lung disease mechanisms and how they are modified by therapeutic intervention, in this case ETI. This study identifies imbalances in pro- and anti- inflammatory proteins in sputum that partially resolve with ETI even in those achieving normal spirometry values. This post-ETI intermediate state could contribute to ongoing airway damage and therefore its relevance to clinical outcomes needs to be established.

The relationship between lung disease severity and the sputum proteome in cystic fibrosis.

BACKGROUND: Proteomics can reveal molecular pathways of disease and provide translational perspectives to inform clinical decision making. Although several studies have previously reported the cystic fibrosis airway proteome, the relationship with severity of lung disease has not been characterised. The objectives of this observational study were to investigate differences in the CF sputum proteome associated with disease severity and identify potential markers of disease with translational potential. METHODS: Sputum samples from healthy volunteers and cystic fibrosis subjects (some prescribed modulator therapies) were analysed using liquid-chromatography tandem mass spectrometry. Severity of lung disease was based on baseline spirometry (percentage predicted forced expiratory volume in 1 s, FEV1%). RESULTS: Multiple sputum proteins (108 increased; 202 decreased) were differentially expressed in CF (n = 38) and healthy volunteers (n = 32). Using principal component analysis and hierarchical clustering, differences in sputum proteome were observed associated with progressive lung function impairment. In CF subjects, baseline FEV1% correlated with 87 proteins (positive correlation n = 20, negative n = 67); most were either neutrophil derived, or opposed neutrophil-driven oxidant and protease activity. CONCLUSION: Predictable and quantifiable changes in the CF sputum proteome occurred associated with progressive lung function impairment, some of which might have value as markers of disease severity in CF sputum. Further work validating these markers in other patient cohorts and exploring their clinical utility is needed.

Plasmon-Mediated Chiroptical Second Harmonic Generation from Seemingly Achiral Gold Nanorods.

Throughout nature, simple rules explain complex phenomena, such as the selective interaction of chiral objects with circularly polarized light. Here, we demonstrate chiroptical signals from gold nanorods, which are seemingly achiral structures. Shape anisotropy due to atomic-level faceting and rounding at the tips of nanorods, which are free of chiral surface ligands, induces linear-to-circular polarization modulation during second harmonic generation. The intrinsic nanorod chiroptical response is increased by plasmon-resonant excitation, which preferentially amplifies circularly polarized harmonic signals. This structure-plasmon interplay is uniquely resolved by polarization-resolved second harmonic generation measurements. The material's second-order polarizability is the product of the structure-dependent lattice-normal susceptibility and local surface plasmon field vectors. Synthetically scalable plasmon-supporting nanorods that amplify small circular dichroism signals provide a simple, assembly-free platform for chiroptical transduction.

Self-regulation at work.

Self-regulation at work is conceived in terms of within-person processes that occur over time. These processes are proposed to occur within a hierarchical framework of negative feedback systems that operate at different levels of abstraction and with different time cycles. Negative feedback systems respond to discrepancies in a manner that reduces deviations from standards (i.e., goals). This is in contrast to positive feedback systems in which discrepancies are created, which can lead to instability. We organize our discussion around four hierarchical levels-self, achievement task, lower-level task action, and knowledge/working memory. We theorize that these levels are loosely connected by multiple constraints and that both automatic and more conscious processes are essential to self-regulation. Within- and cross-level affective and cognitive processes interact within this system to motivate goal-related behaviors while also accessing needed knowledge and protecting current intentions from interference. Complications common in the work setting (as well as other complex, real-life settings) such as the simultaneous pursuit of multiple goals, the importance of knowledge access and expertise, and team and multiperson processes are also discussed. Finally, we highlight the usefulness of newer research methodologies and data-analytic techniques for examining such hierarchical, dynamic, within-person processes.