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It remains unclear which individuals with subthreshold depression benefit most from psychological intervention, and what long-term effects this has on symptom deterioration, response and remission.
Aims
To synthesise psychological intervention benefits in adults with subthreshold depression up to 2 years, and explore participant-level effect-modifiers.
Method
Randomised trials comparing psychological intervention with inactive control were identified via systematic search. Authors were contacted to obtain individual participant data (IPD), analysed using Bayesian one-stage meta-analysis. Treatment–covariate interactions were added to examine moderators. Hierarchical-additive models were used to explore treatment benefits conditional on baseline Patient Health Questionnaire 9 (PHQ-9) values.
Results
IPD of 10 671 individuals (50 studies) could be included. We found significant effects on depressive symptom severity up to 12 months (standardised mean-difference [s.m.d.] = −0.48 to −0.27). Effects could not be ascertained up to 24 months (s.m.d. = −0.18). Similar findings emerged for 50% symptom reduction (relative risk = 1.27–2.79), reliable improvement (relative risk = 1.38–3.17), deterioration (relative risk = 0.67–0.54) and close-to-symptom-free status (relative risk = 1.41–2.80). Among participant-level moderators, only initial depression and anxiety severity were highly credible (P > 0.99). Predicted treatment benefits decreased with lower symptom severity but remained minimally important even for very mild symptoms (s.m.d. = −0.33 for PHQ-9 = 5).
Conclusions
Psychological intervention reduces the symptom burden in individuals with subthreshold depression up to 1 year, and protects against symptom deterioration. Benefits up to 2 years are less certain. We find strong support for intervention in subthreshold depression, particularly with PHQ-9 scores ≥ 10. For very mild symptoms, scalable treatments could be an attractive option.
Motor neuron disease (MND) is a progressive, fatal, neurodegenerative condition that affects motor neurons in the brain and spinal cord, resulting in loss of the ability to move, speak, swallow and breathe. Acceptance and commitment therapy (ACT) is an acceptance-based behavioural therapy that may be particularly beneficial for people living with MND (plwMND). This qualitative study aimed to explore plwMND’s experiences of receiving adapted ACT, tailored to their specific needs, and therapists’ experiences of delivering it.
Method:
Semi-structured qualitative interviews were conducted with plwMND who had received up to eight 1:1 sessions of adapted ACT and therapists who had delivered it within an uncontrolled feasibility study. Interviews explored experiences of ACT and how it could be optimised for plwMND. Interviews were audio recorded, transcribed and analysed using framework analysis.
Results:
Participants were 14 plwMND and 11 therapists. Data were coded into four over-arching themes: (i) an appropriate tool to navigate the disease course; (ii) the value of therapy outweighing the challenges; (iii) relevance to the individual; and (iv) involving others. These themes highlighted that ACT was perceived to be acceptable by plwMND and therapists, and many participants reported or anticipated beneficial outcomes in the future, despite some therapeutic challenges. They also highlighted how individual factors can influence experiences of ACT, and the potential benefit of involving others in therapy.
Conclusions:
Qualitative data supported the acceptability of ACT for plwMND. Future research and clinical practice should address expectations and personal relevance of ACT to optimise its delivery to plwMND.
Key learning aims
(1) To understand the views of people living with motor neuron disease (plwMND) and therapists on acceptance and commitment therapy (ACT) for people living with this condition.
(2) To understand the facilitators of and barriers to ACT for plwMND.
(3) To learn whether ACT that has been tailored to meet the specific needs of plwMND needs to be further adapted to potentially increase its acceptability to this population.
To analyse the rate of contralateral nodal metastasis in human papillomavirus (HPV)-associated oropharyngeal carcinoma and identify the patient cohorts that would benefit from bilateral neck treatment.
Methods
A retrospective cohort review was performed on 110 HPV-positive oropharyngeal carcinoma patients who underwent transoral robotic surgery and bilateral neck dissections from 2012 to 2022. The primary outcome was to investigate the pathological incidence and location of contralateral neck node metastasis.
Results
The contralateral nodal disease rate was 12.7 per cent (n = 14), of which 2 patients (2 per cent) were occult findings, with comparable results between tongue base and tonsil sub-groups. The most commonly involved contralateral nodal station was level II (11 of 110 patients, 10 per cent). The presence of extra-nodal extension and multiple ipsilateral positive nodes was associated with increased risk of contralateral nodal disease.
Conclusion
The incidence of contralateral nodal and occult disease in the studied cohort is low. The characteristics of patients who may benefit from bilateral neck treatment were demonstrated.
Social health (SH) markers, including marital status, contact frequency, network size, and social support, have been linked with increased cognitive capability. However, the underlying mechanisms remain poorly understood. We aim to investigate whether depression symptoms and inflammatory biomarkers mediate associations between SH and cognitive outcomes.
Methods:
We used data from waves 1-9 of the English Longitudinal Study of Ageing, involving 7,136 participants aged 50 or older at baseline. First, we examined associations between SH (wave 1) and depression and inflammatory biomarkers (C-reactive protein (CRP) and fibrinogen) (wave 2) using linear regression models. Second, we tested associations between a) SH and b) depression and inflammation with subsequent standardised verbal fluency and memory in wave 3 and change between waves 3-9, indexed using slopes derived from multilevel models. We adjusted for age, sex, socio-economic position, cardiovascular disease, basic and instrumental activities of daily living, health behaviours, and baseline depression symptoms and cognition. We will also conduct causal mediation analysis.
Results:
All SH markers, except contact frequency, were associated with lower subsequent depression, but not inflammatory biomarkers. Greater contact frequency (e.g. once-twice a week vs <once per year: β=0.18 [0.01, 0.36]) and less negative support (β=0.02 [0.00, 0.03]) were associated with higher verbal fluency. Larger network size (>6 people vs none: β=0.007SD/year [0.001, 0.012]), less negative (β=0.001SD/year [0.001, 0.002]) and more positive support (β=0.001SD/year [0.000, 0.001]) were linked with slower memory decline, and more positive support predicted slower verbal fluency decline (β=0.001SD/year [0.000, 0.001]). Depression symptoms were associated with lower memory and verbal fluency, and faster memory decline (β=-0.001SD/year [-0.001, -0.000]) and verbal fluency (β=-0.001SD/year [-0.001, -0.000]). CRP was associated with lower verbal fluency (β=-0.02 [-0.04, 0.00]), whereas fibrinogen was linked with faster memory decline (β=-0.001SD/year [-0.003, -0.000]).
Conclusion:
Depression symptoms and SH showed associations with subsequent cognitive capability and change. SH was linked with lower depression, but not inflammatory biomarkers. Findings highlight the potential for depression to underpin associations between SH and cognition, a pathway which we will test using causal mediation analysis. We will also examine whether findings replicate in the Swedish National Study of Aging and Care in Kungsholmen.
Cancer health research relies on large-scale cohorts to derive generalizable results for different populations. While traditional epidemiological cohorts often use costly random sampling or self-motivated, preselected groups, a shift toward health system-based cohorts has emerged. However, such cohorts depend on participants remaining within a single system. Recent consumer engagement models using smartphone-based communication, driving projects, and social media have begun to upend these paradigms.
Methods:
We initiated the Healthy Oregon Project (HOP) to support basic and clinical cancer research. HOP study employs a novel, cost-effective remote recruitment approach to effectively establish a large-scale cohort for population-based studies. The recruitment leverages the unique email account, the HOP website, and social media platforms to direct smartphone users to the study app, which facilitates saliva sample collection and survey administration. Monthly newsletters further facilitate engagement and outreach to broader communities.
Results:
By the end of 2022, the HOP has enrolled approximately 35,000 participants aged 18–100 years (median = 44.2 years), comprising more than 1% of the Oregon adult population. Among those who have app access, ∼87% provided consent to genetic screening. The HOP monthly email newsletters have an average open rate of 38%. Efforts continue to be made to improve survey response rates.
Conclusion:
This study underscores the efficacy of remote recruitment approaches in establishing large-scale cohorts for population-based cancer studies. The implementation of the study facilitates the collection of extensive survey and biological data into a repository that can be broadly shared and supports collaborative clinical and translational research.
Anxiety and depression are frequently comorbid yet phenotypically distinct. This study identifies differences in the clinically observable phenome across a wide variety of physical and mental disorders comparing patients with diagnoses of depression without anxiety, anxiety without depression, or both depression and anxiety.
Methods
Using electronic health records for 14 994 participants with depression and/or anxiety in the Mayo Clinic Biobank, a phenotype-based phenome-wide association study (Phe2WAS) was performed to test for differences between these groups across a broad range of clinical diagnoses observed in the electronic health record. Additional analyses were performed to determine the temporal sequencing of diagnoses.
Results
Compared to patients diagnosed only with anxiety, those diagnosed only with depression were more likely to have diagnoses of obesity (OR 1.75; p = 1 × 10−27), sleep apnea (OR 1.71; p = 1 × 10−22), and type II diabetes (OR 1.74; p = 9 × 10−18). Compared to those diagnosed only with depression, those diagnosed only with anxiety were more likely to have diagnoses of palpitations (OR 1.91; p = 2 × 10−25), benign skin neoplasms (OR 1.61; p = 2 × 10−17), and cardiac dysrhythmias (OR 1.45; p = 2 × 10−12). Patients with comorbid depression and anxiety were more likely to have diagnoses of other mental health disorders, substance use disorders, sleep problems, and gastroesophageal reflux relative to isolated depression.
Conclusions
While depression and anxiety are closely related, this study suggests that phenotypic distinctions exist between depression and anxiety. Improving phenotypic characterization within the broad categories of depression and anxiety could improve the clinical assessment of depression and anxiety.
Individuals living with severe mental illness can have significant emotional, physical and social challenges. Collaborative care combines clinical and organisational components.
Aims
We tested whether a primary care-based collaborative care model (PARTNERS) would improve quality of life for people with diagnoses of schizophrenia, bipolar disorder or other psychoses, compared with usual care.
Method
We conducted a general practice-based, cluster randomised controlled superiority trial. Practices were recruited from four English regions and allocated (1:1) to intervention or control. Individuals receiving limited input in secondary care or who were under primary care only were eligible. The 12-month PARTNERS intervention incorporated person-centred coaching support and liaison work. The primary outcome was quality of life as measured by the Manchester Short Assessment of Quality of Life (MANSA).
Results
We allocated 39 general practices, with 198 participants, to the PARTNERS intervention (20 practices, 116 participants) or control (19 practices, 82 participants). Primary outcome data were available for 99 (85.3%) intervention and 71 (86.6%) control participants. Mean change in overall MANSA score did not differ between the groups (intervention: 0.25, s.d. 0.73; control: 0.21, s.d. 0.86; estimated fully adjusted between-group difference 0.03, 95% CI −0.25 to 0.31; P = 0.819). Acute mental health episodes (safety outcome) included three crises in the intervention group and four in the control group.
Conclusions
There was no evidence of a difference in quality of life, as measured with the MANSA, between those receiving the PARTNERS intervention and usual care. Shifting care to primary care was not associated with increased adverse outcomes.
The developmental absence (agenesis) of the corpus callosum (AgCC) is a congenital brain malformation associated with risk for a range of neuropsychological difficulties. Inhibitory control outcomes, including interference control and response inhibition, in children with AgCC are unclear. This study examined interference control and response inhibition: 1) in children with AgCC compared with typically developing (TD) children, 2) in children with different anatomical features of AgCC (complete vs. partial, isolated vs. complex), and 3) associations with white matter volume and microstructure of the anterior (AC) and posterior commissures (PC) and any remnant corpus callosum (CC).
Methods:
Participants were 27 children with AgCC and 32 TD children 8–16 years who completed inhibitory control assessments and brain MRI to define AgCC anatomical features and measure white matter volume and microstructure.
Results:
The AgCC cohort had poorer performance and higher rates of below average performance on inhibitory control measures than TD children. Children with complex AgCC had poorer response inhibition performance than children with isolated AgCC. While not statistically significant, there were select medium to large effect sizes for better inhibitory control associated with greater volume and microstructure of the AC and PC, and with reduced volume and microstructure of the remnant CC in partial AgCC.
Conclusions:
This study provides evidence of inhibitory control difficulties in children with AgCC. While the sample was small, the study found preliminary evidence that the AC (f2=.18) and PC (f2=.30) may play a compensatory role for inhibitory control outcomes in the absence of the CC.
HIV-associated neurocognitive disorders (HANDs) are prevalent in older people living with HIV (PLWH) worldwide. HAND prevalence and incidence studies of the newly emergent population of combination antiretroviral therapy (cART)-treated older PLWH in sub-Saharan Africa are currently lacking. We aimed to estimate HAND prevalence and incidence using robust measures in stable, cART-treated older adults under long-term follow-up in Tanzania and report cognitive comorbidities.
Design:
Longitudinal study
Participants:
A systematic sample of consenting HIV-positive adults aged ≥50 years attending routine clinical care at an HIV Care and Treatment Centre during March–May 2016 and followed up March–May 2017.
Measurements:
HAND by consensus panel Frascati criteria based on detailed locally normed low-literacy neuropsychological battery, structured neuropsychiatric clinical assessment, and collateral history. Demographic and etiological factors by self-report and clinical records.
Results:
In this cohort (n = 253, 72.3% female, median age 57), HAND prevalence was 47.0% (95% CI 40.9–53.2, n = 119) despite well-managed HIV disease (Mn CD4 516 (98-1719), 95.5% on cART). Of these, 64 (25.3%) were asymptomatic neurocognitive impairment, 46 (18.2%) mild neurocognitive disorder, and 9 (3.6%) HIV-associated dementia. One-year incidence was high (37.2%, 95% CI 25.9 to 51.8), but some reversibility (17.6%, 95% CI 10.0–28.6 n = 16) was observed.
Conclusions:
HAND appear highly prevalent in older PLWH in this setting, where demographic profile differs markedly to high-income cohorts, and comorbidities are frequent. Incidence and reversibility also appear high. Future studies should focus on etiologies and potentially reversible factors in this setting.
There is global interest in the reconfiguration of community mental health services, including primary care, to improve clinical and cost effectiveness.
Aims
This study seeks to describe patterns of service use, continuity of care, health risks, physical healthcare monitoring and the balance between primary and secondary mental healthcare for people with severe mental illness in receipt of secondary mental healthcare in the UK.
Method
We conducted an epidemiological medical records review in three UK sites. We identified 297 cases randomly selected from the three participating mental health services. Data were manually extracted from electronic patient medical records from both secondary and primary care, for a 2-year period (2012–2014). Continuous data were summarised by mean and s.d. or median and interquartile range (IQR). Categorical data were summarised as percentages.
Results
The majority of care was from secondary care practitioners: of the 18 210 direct contacts recorded, 76% were from secondary care (median, 36.5; IQR, 14–68) and 24% were from primary care (median, 10; IQR, 5–20). There was evidence of poor longitudinal continuity: in primary care, 31% of people had poor longitudinal continuity (Modified Modified Continuity Index ≤0.5), and 43% had a single named care coordinator in secondary care services over the 2 years.
Conclusions
The study indicates scope for improvement in supporting mental health service delivery in primary care. Greater knowledge of how care is organised presents an opportunity to ensure some rebalancing of the care that all people with severe mental illness receive, when they need it. A future publication will examine differences between the three sites that participated in this study.
Emotional cognition and effective interpretation of affective information is an important factor in social interactions and everyday functioning, and difficulties in these areas may contribute to aetiology and maintenance of mental health conditions. In younger people with depression and anxiety, research suggests significant alterations in behavioural and brain activation aspects of emotion processing, with a tendency to appraise neutral stimuli as negative and attend preferentially to negative stimuli. However, in ageing, research suggests that emotion processing becomes subject to a ‘positivity effect’, whereby older people attend more to positive than negative stimuli.
Aims
This review examines data from studies of emotion processing in Late-Life Depression and Late-Life Anxiety to attempt to understand the significance of emotion processing variations in these conditions, and their interaction with changes in emotion processing that occur with ageing.
Method
We conducted a systematic review following PRISMA guidelines. Articles that used an emotion-based processing task, examined older persons with depression or an anxiety disorder and included a healthy control group were included.
Results
In Late-Life Depression, there is little consistent behavioural evidence of impaired emotion processing, but there is evidence of altered brain circuitry during these processes. In Late-Life Anxiety and Post-Traumatic Stress disorder, there is evidence of interference with processing of negative or threat-related words.
Conclusions
How these findings fit with the positivity bias of ageing is not clear. Future research is required in larger groups, further examining the interaction between illness and age and the significance of age at disease onset.
We describe an ultra-wide-bandwidth, low-frequency receiver recently installed on the Parkes radio telescope. The receiver system provides continuous frequency coverage from 704 to 4032 MHz. For much of the band (
${\sim}60\%$
), the system temperature is approximately 22 K and the receiver system remains in a linear regime even in the presence of strong mobile phone transmissions. We discuss the scientific and technical aspects of the new receiver, including its astronomical objectives, as well as the feed, receiver, digitiser, and signal processor design. We describe the pipeline routines that form the archive-ready data products and how those data files can be accessed from the archives. The system performance is quantified, including the system noise and linearity, beam shape, antenna efficiency, polarisation calibration, and timing stability.
Decisions on the use of nature reflect the values and rights of individuals, communities and society at large. The values of nature are expressed through cultural norms, rules and legislation, and they can be elicited using a wide range of tools, including those of economics. None of the approaches to elicit peoples’ values are neutral. Unequal power relations influence valuation and decision-making and are at the core of most environmental conflicts. As actors in sustainability thinking, environmental scientists and practitioners are becoming more aware of their own posture, normative stance, responsibility and relative power in society. Based on a transdisciplinary workshop, our perspective paper provides a normative basis for this new community of scientists and practitioners engaged in the plural valuation of nature.
To determine whether the Society for Healthcare Epidemiology of America (SHEA) and the Infectious Diseases Society of America (IDSA) Clostridioides difficile infection (CDI) severity criteria adequately predicts poor outcomes.
Design:
Retrospective validation study.
Setting and participants:
Patients with CDI in the Veterans’ Affairs Health System from January 1, 2006, to December 31, 2016.
Methods:
For the 2010 criteria, patients with leukocytosis or a serum creatinine (SCr) value ≥1.5 times the baseline were classified as severe. For the 2018 criteria, patients with leukocytosis or a SCr value ≥1.5 mg/dL were classified as severe. Poor outcomes were defined as hospital or intensive care admission within 7 days of diagnosis, colectomy within 14 days, or 30-day all-cause mortality; they were modeled as a function of the 2010 and 2018 criteria separately using logistic regression.
Results:
We analyzed data from 86,112 episodes of CDI. Severity was unclassifiable in a large proportion of episodes diagnosed in subacute care (2010, 58.8%; 2018, 49.2%). Sensitivity ranged from 0.48 for subacute care using 2010 criteria to 0.73 for acute care using 2018 criteria. Areas under the curve were poor and similar (0.60 for subacute care and 0.57 for acute care) for both versions, but negative predictive values were >0.80.
Conclusions:
Model performances across care settings and criteria versions were generally poor but had reasonably high negative predictive value. Many patients in the subacute-care setting, an increasing fraction of CDI cases, could not be classified. More work is needed to develop criteria to identify patients at risk of poor outcomes.
Protected areas are central to global efforts to prevent species extinctions, with many countries investing heavily in their establishment. Yet the designation of protected areas alone can only abate certain threats to biodiversity. Targeted management within protected areas is often required to achieve fully effective conservation within their boundaries. It remains unclear what combination of protected area designation and management is needed to remove the suite of processes that imperil species. Here, using Australia as a case study, we use a dataset on the pressures facing threatened species to determine the role of protected areas and management in conserving imperilled species. We found that protected areas that are not resourced for threat management could remove one or more threats to 1,185 (76%) species and all threats to very few (n = 51, 3%) species. In contrast, a protected area network that is adequately resourced to manage threatening processes within their boundary could remove one or more threats to almost all species (n = 1,551; c. 100%) and all threats to almost half (n = 740, 48%). However, 815 (52%) species face one or more threats that require coordinated conservation actions that protected areas alone could not remove. This research shows that investing in the continued expansion of Australia's protected area network without providing adequate funding for threat management within and beyond the existing protected area network will benefit few threatened species. These findings highlight that as the international community expands the global protected area network in accordance with the 2020 Strategic Plan for Biodiversity, a greater emphasis on the effectiveness of threat management is needed.
Connectedness is a central dimension of personal recovery from severe mental illness (SMI). Research reports that people with SMI have lower social capital and poorer-quality social networks compared to the general population.
Aims
To identify personal well-being network (PWN) types and explore additional insights from mapping connections to places and activities alongside social ties.
Method
We carried out 150 interviews with individuals with SMI and mapped social ties, places and activities and their impact on well-being. PWN types were developed using social network analysis and hierarchical k-means clustering of this data.
Results
Three PWN types were identified: formal and sparse; family and stable; and diverse and active. Well-being and social capital varied within and among types. Place and activity data indicated important contextual differences within social connections that were not found by mapping social networks alone.
Conclusions
Place locations and meaningful activities are important aspects of people's social worlds. Mapped alongside social networks, PWNs have important implications for person-centred recovery approaches through providing a broader understanding of individual's lives and resources.
Objectives: Agenesis of the corpus callosum (AgCC), characterized by developmental absence of the corpus callosum, is one of the most common congenital brain malformations. To date, there are limited data on the neuropsychological consequences of AgCC and factors that modulate different outcomes, especially in children. This study aimed to describe general intellectual, academic, executive, social and behavioral functioning in a cohort of school-aged children presenting for clinical services to a hospital and diagnosed with AgCC. The influences of age, social risk and neurological factors were examined. Methods: Twenty-eight school-aged children (8 to 17 years) diagnosed with AgCC completed tests of general intelligence (IQ) and academic functioning. Executive, social and behavioral functioning in daily life, and social risk, were estimated from parent and teacher rated questionnaires. MRI findings reviewed by a pediatric neurologist confirmed diagnosis and identified brain characteristics. Clinical details including the presence of epilepsy and diagnosed genetic condition were obtained from medical records. Results: In our cohort, ~50% of children experienced general intellectual, academic, executive, social and/or behavioral difficulties and ~20% were functioning at a level comparable to typically developing children. Social risk was important for understanding variability in neuropsychological outcomes. Brain anomalies and complete AgCC were associated with lower mathematics performance and poorer executive functioning. Conclusions: This is the first comprehensive report of general intellectual, academic, executive social and behavioral consequences of AgCC in school-aged children. The findings have important clinical implications, suggesting that support to families and targeted intervention could promote positive neuropsychological functioning in children with AgCC who come to clinical attention. (JINS, 2018, 24, 445–455)
Artemether (ATM) cardiotoxicity, its short half-life and low oral bioavailability are the major limiting factors for its use to treat malaria. The purposes of this work were to study free-ATM and ATM-loaded poly-ε-caprolactone nanocapules (ATM-NC) cardiotoxicity and oral efficacy on Plasmodium berghei-infected mice. ATM-NC was obtained by interfacial polymer deposition and ATM was associated with polymeric NC oily core. For cardiotoxicity evaluation, male black C57BL6 uninfected or P. berghei-infected mice received, by oral route twice daily/4 days, vehicle (sorbitol/carboxymethylcellulose), blank-NC, free-ATM or ATM-NC at doses 40, 80 or 120 mg kg−1. Electrocardiogram (ECG) lead II signal was obtained before and after treatment. For ATM efficacy evaluation, female P. berghei-infected mice were treated the same way. ATM-NC improved antimalarial in vivo efficacy and reduced mice mortality. Free-ATM induced significantly QT and QTc intervals prolongation. ATM-NC (120 mg kg−1) given to uninfected mice reduced QT and QTc intervals prolongation 34 and 30%, respectively, compared with free-ATM. ATM-NC given to infected mice also reduced QT and QTc intervals prolongation, 28 and 27%, respectively. For the first time, the study showed a nanocarrier reducing cardiotoxicity of ATM given by oral route and it was more effective against P. berghei than free-ATM as monotherapy.
Analysis of in situ neutron powder diffraction data collected for the porous framework material Zn(hba) during gas adsorption reveals a two-stage response of the host lattice to increasing CO2 guest concentration, suggesting progressive occupation of multiple CO2 adsorption sites with different binding strengths. The response of the lattice to moderate CH4 guest concentrations is virtually indistinguishable from the response to CO2, demonstrating that the influence of host–guest interactions on the Zn(hba) framework is defined more strongly by the concentration than by the identity of the guests.